|
 |
REVIEW ARTICLE |
|
Year : 2011 | Volume
: 2
| Issue : 4 | Page : 215-222 |
|
|
A review on mucoadhesive polymer used in nasal drug delivery system
Mayank Chaturvedi, Manish Kumar, Kamla Pathak
Department of Pharmaceutics, Rajiv Academy for Pharmacy, Mathura, Uttar Pradesh, India
Date of Web Publication | 16-Dec-2011 |
Correspondence Address: Mayank Chaturvedi Department of Pharmaceutics, Rajiv Academy for Pharmacy, NH-2, Mathura, Delhi Highway, Mathura, Uttar Pradesh India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/2231-4040.90876
Abstract | | |
This update review is on mucoadhesive polymers used in nasal dosage forms. The nasal mucosa provides a potentially good route for systemic drug delivery. One of the most important features of the nasal route is that it avoids first-pass hepatic metabolism, thereby reducing metabolism. The application of mucoadhesive polymers in nasal drug delivery systems has gained to promote dosage form residence time in the nasal cavity as well as improving intimacy of contact with absorptive membranes of the biological system. The various new technology uses in development of nasal drug delivery dosage forms are discussed. The various dosage forms are vesicular carriers (liposome, noisome), nanostructured particles, prodrugs, in situ gelling system with special attention to in vivo studies. Keywords: In vivo ,mucoadhesive polymers, nasal drug delivery system
How to cite this article: Chaturvedi M, Kumar M, Pathak K. A review on mucoadhesive polymer used in nasal drug delivery system. J Adv Pharm Technol Res 2011;2:215-22 |
How to cite this URL: Chaturvedi M, Kumar M, Pathak K. A review on mucoadhesive polymer used in nasal drug delivery system. J Adv Pharm Technol Res [serial online] 2011 [cited 2023 Mar 29];2:215-22. Available from: https://www.japtr.org/text.asp?2011/2/4/215/90876 |
Introduction | |  |
Drugs have been administrated nasally for therapeutic and recreational purpose since ancient times. Psychotropic drugs and hallucinogens were snuffed for these purposes by the Indian of South America, and this practice is currently widespread among abusers of cocaine and heroin. The interest in and importance of the systemic effects of the drugs administrated through the nasal route have expanded over recent decades.
Nasal administration offers an interesting alternative for achieving systemic drug effects to the parenteral route, which can be inconvenient or oral administration, which can result in unacceptably low bioavailabilities. The nasal epithelium is a highly permeable monolayer, the sub mucosa is richly vascularized, and hepatic first-pass metabolism is avoided after nasal administration. Other attractive features include the rather large surface area of the nasal cavity and the relatively high blood flow, which promotes rapid absorption. [1] Furthermore, self-medication is easy and convenient.
Advantages of Nasal Route
Systemic nasal absorption of drug is a new attractive alternative to parenteral drug delivery system, as it offers the following advantages: [2]- Transnasal delivery provides direct entry of drug into systemic circulation, e.g., Thiomeerosal, Amastatin, Puromycin, Nifedipine, etc.
- Unlike the skin, nasal mucosa is not constructed from the keratinized stratum corneum. The subepithelial layer of the nasal mucosa with numerous microvilli is highly vascularized, with large and fenestrated capillaries facilitating rapid absorption.
- The rate and extent of absorption as well as plasma concentration vs time profiles are comparable with I.V. administration.
- Avoidance of first pass elimination, gut wall metabolism, and destruction in gastrointestinal tract.
- Various nasal drug delivery systems are available for user-friendly noninvasive painless application.
Limitation of Nasal Drug Delivery System
There is risk of local side effects and irreversible damage of the cilia on the nasal mucosa, both from the drug substances and from the constituents added to the dosage forms. [2]
- Certain compounds when used as absorption enhancers may disrupt and even dissolve the nasal membrane in high concentration.
- Nasal atrophic rhinitis and severe vasomotor rhinitis can reduce the capacity of nasal absorption, e.g., Caerulein.
- There could be mechanical loss of the dosage form into the other parts of the respiratory tract like lungs.
- Untoward immunogenic effects might arise with the route.
Low bioavailability results from enzymatic degradation and metabolism at mucosal site and low residence time.
The Nasal Cavity
The nasal cavity has an important protective function in that it filters, warms, and humidifies the inhaled air before it reaches the lower airways. Any inhaled particles or microorganisms are trapped by the hairs in the nasal vestibule or by the mucus layer covering the respiratory area of the nasal cavity. Due to the mucociliary clearance mechanism, layer will gradually carry such particulates to the back of the throat, down the esophagus, and further into the gastrointestinal tract. Furthermore, the nasal layer mucosa has a metabolic capacity that will help convert endogenous materials into compounds that lies beneath are more easily eliminated. [3]
Nasal Anatomy and Physiology
The nostrils are a pair of nasal cavities divided by a nasal septum; their total volume is approximately 15 cc 3 , with a total surface area of 150 cm 2 . These nasal cavities are covered by a mucosa with a thickness of 2 to 4 mm, whose function in human beings is 20% olfactory and 80% respiratory. The nasal epithelium has a relatively high permeability, and only two cell layers separate the nasal lumen from the dense blood vessel network in the lamina propria cavity which is lined with three types of epithelia: Squamous, respiratory, and olfactory [Figure 1]. [4],[5] | Figure 1: Lateral wall of the nasal cavity. (A) Squamous epithelium, (B) inferior turbinate, (C) middle turbinate, (D) superior turbinate, (E) frontal sinus, (F) respiratory epithelium, (G) olfactory epithelium, (H) sphenoidal sinus, and (I) faucial tonsil
Click here to view |
The mucosa in the anterior part of the nose is squamous and without cilia. Within the anterior nostrils, a transitional epithelium is found that precedes the respiratory epithelium. The olfactory epithelium is present in the posterior part of the nasal cavity. The epithelium contains ciliary cells that produce a unidirectional flow of mucus toward the pharynx. [6] A drug deposited posteriorly in the nose is cleared more rapidly from the nasal cavity than a drug deposited anteriorly, because clearance is slower at the anterior part of the nose than in the more ciliated posterior. [7]
Nasal Mucosal
The nasal lining has the same lining as the rest of the respiratory tract with pseudostratified ciliated columnar epithelium. There are up to 200 cilia per cell whose tips lie in the superficial gel layer [Figure 2]. At the anterior end of the inferior and middle turbinate, which is the area which has most contact with inspired air, there can be metaplasia with cuboidal cells which have no cilia.
Various Dosage Forms given by Nasal Route | |  |
Solution and Sprays
The drug solutions are nasally administered as nasal drops, sprays, and as metered dose nebulizer. The dose of the active ingredient administered depends upon the volume of drug and the concentration of drug in the formulation. The therapeutic levels of nitroglycerine, 3 ng/ml in central venous blood, 1.7 ng/ml in arterial blood, and 0.4 ng/ml in peripheral venous blood were achieved within 2 minutes following intranasal administration of 0.8 mg/ml of nitroglycerine in normal saline. The effect of formulation variables such as dose of active ingredient, pH of the solution, and its osmolarity on nasal absorption has been reported by various researchers. [8]
Suspensions
Suspensions for nasal administration are prepared by suspending the micronized drug in a liquid diluent or carrier suitable for application to the nasal mucosa. The preparation of suspension form gave a better insulin uptake and blood glucose reduction compared with that from the solution. [9]
Powders
Powder dosage forms of drugs for nasal administration offer several advantages over liquid formulations. In the powder form, the chemical stability of the drug is increased, a preservative in the formulation is not required, and it is possible to administer larger doses of drugs. Powder form is suitable for number of non-peptide drugs and is well suited for peptide drugs. [10]
Polymer-based powder formulations show no adhesion until their absorption of mucus occurs on the nasal mucosa surface. This allows easy application to the nasal cavity by metered dose in sufflation even if the polymer is highly mucoadhesive. [11] In addition, liquid preparations are more easily cleared to the nasopharynx and oropharynx from where they enter the posterior part of the tongue. [12]
Therefore, administration of nasal powders may increase patient compliance, especially if the smell and taste of the delivered drug is unacceptable. After getting in contact with the nasal mucosa, polymer-based powders are believed to form a viscous gel following absorbing water from the nasal mucus [Figure 2]. Then, the free polymer chains penetrating into the tissue crevices can hold back the ciliary movement, which will increase the retention time of the drugs in the nasal cavity. [13]
Dry powder formulations can also avoid the utilization of preservatives and freeze storage, because they do not support microbial growth and are more stable than solution. For these reasons, the dried powder is the most commonly studied formulation for the nasal drug delivery, including small hydrophobic drugs, peptide drugs, and vaccine. [14] prepared dry powder nasal influenza vaccine formulation by using spray-freeze-drying method; the results indicated that the powders were amorphous and more stable with respect to liquid formulations. In vivo experiments demonstrated that the powders significantly increased residence time in rats and elicit enhanced serum and mucosal antibody response.
Nasal Particulate Drug Delivery System
Nasal particulate systems using mucoadhesive polymers as carriers include microparticle/sphere and nanoparticle. Particulate drug carrier systems administered through nasal mucosa may protect the drug from enzymatic degradation, increase the drug dissolution rate, intensify the contact of the formulation with the mucosa, enhance the uptake by the epithelium, and act as a controlled release system resulting in prolonged blood concentrations.[15],[16] Among the polymers widely used as nasal drug particulate carrier, the positively charged polymers such as chitosan and aminated gelatin are most attractive because of their hydrogel nature which leads to opening of the tight junctions and their intimate contact with the negatively charged mucosa membrane. [17] In vivo evaluation in rabbits has proved that chitosan nanoparticles were able to improve the nasal absorption to a great extent compared with chitosan solution due to the intensified contact of the nanoparticle with the nasal mucosa as compared with chitosan solutions.[18]
It has been believed that nanoparticles possess superiority over microspheres as nasal drug carrier because their larger surface area results in more intimate contact with the mucosa, which leads to higher local concentration gradient.[19]
Moreover, nanoparticles cross the mucosal epithelium better than microspheres do. Microparticles smaller than 10 μm administered intranasally are believed to be taken up by the M-cells overlaying the nasal-associated lymphoid tissue (NALT) and transported to sub-mucosal layers. However, in case of the nanoparticles, besides the M-cell-associated phagocytosis, the epithelial cells are also involved in the transport of nanoparticles by internalization. [20]
Recent study by showed that FITC-albumin-loaded chitosan nanoparticles, when administered in the nasal cavity, were able to cross the mucosal layer, taken up by rat nasal epithelia and NALT cells. This property of nanoparticles provides a good indication of their potential as gene and vaccine carriers.[21]
Teijeiro-Osorio et al. found that the transfection efficiency of the nanoparticles loaded with pSEAP (100-200 nm) was higher than the naked DNA (control). [22]
Recently, many studies confirmed that association of vaccines to the nanoparticulate systems has shown to enhance the antigen uptake by nasal lymphoid tissues. [23]
Semi-Solid Dosage Forms | |  |
A gel is a soft, solid or solid-like material consisting of two or more components, one of which is a liquid, present in substantial quantity. A gel should, on a time scale of seconds, not flow under the influence of its own weight. The solid-like characteristics of gels can be defined in terms of two dynamic mechanical properties: An elastic modulus, G'(ù), which exhibits a pronounced plateau extending to time at least of the order of second; and a viscous modulus, G"(ù), which is considerably smaller than G'(ù). The first biological uses of gels (polymerized methyl methacrylate) were presented by the institute for Macromolecular Chemistry in Prague in 1960 and involved the manufacturing of contact lenses, arteries, etc.
Gelation occurs through the cross-linking of polymer chains, something that can be achieved by (i) covalent bond formation (chemical cross-linking) or (ii) non-covalent bond formation (physical crosslinking). Gels have been used for the delivery of drugs for both systemic and local actions (see the review by Peppas et al.). Many different methods using gels have been reported, including subcutaneous delivery for sustained release, buccal delivery, deliveries to the stomach, colon, rectum, vagina, and nasal.
Gel formulations with suitable rheological properties increase the contact time with the mucosa at the site of absorption. The increased contact time is caused by the mucoadhesive properties of the polymer in the gel and by the rheological properties of the formulation reducing the clearance by the nasal and ocular protective mechanisms. [24],[25],[26]
Mechanism of Mucoadhesion | |  |
The process of mucoadhesion following nasal administration relates to the interaction between the mucoadhesive polymer and the mucus secreted by the sub-mucosal glands.[27] The sequential events that occur during the mucoadhesion include the proper wetting and swelling of the polymer, and intimate contact between the polymer and the nasal mucosa. Then, the swelled mucoadhesive polymer penetrates into the tissue crevices followed by the interpenetration between the polymer chains and protein chains of the mucus [Figure 2].
To obtain sufficient absorption of drugs, first, the formulation should spread well on the nasal mucosa. Therefore, the spreadability is very important for the liquid mucoadhesive formulation, so do the flowability and wettability for the solid mucoadhesive formulation.[28]
Hydration of the polymer (swelling) plays a very important role in mucoadhesion, through which the polymer chains are liberated and interact with the biological tissue. [29] During hydration, there is a dissociation of hydrogen bonds of the polymer chains. When the polymer-water interaction becomes greater than the polymer-polymer interaction, adequate free polymer chains will be available for interaction between the polymer and biological tissue. There is a critical degree of hydration required for optimum mucoadhesion. The incomplete hydration due to the lack of the water leads to incomplete liberation of the polymer chains. On the other hand, an excessive amount of water will weaken the mucoadhesive bonds by over diluting the polymer solution. [30] The polymer chains penetrating into the tissue crevices can hold back the ciliary movement, which will increase the retention time of the drugs in the nasal cavity. Furthermore, the existence of the mucoadhesive carrier also reduces the contact between the drugs and the enzymes existing in the mucosa. These both can enhance the intranasal absorption of hydrophilic drugs (the comparison of ordinary intranasal formulation with mucoadhesive intranasal formulation is showed in [Figure 1]). Apart from these, the dehydration of the epithelial cells after hydration may also temporarily open the tight junctions between the epithelial cells and improve the paracellular absorption of macromolecular drugs. This function of the mucoadhesive polymer is very important for the enhancement of the intranasal absorption of macromolecules weighting above 1 000 Da.[31] Mucoadhesion can slow down the mucociliary clearance, but with time, mucus production will lead to the inordinate swelling of the mucoadhesive polymer and the reduction of the mucoadhesion bond strength, allowing a recovery of normal mucociliary movement rate and the clearance of the polymer from the mucosa.
Although many references indicate that the mucoadhesive polymer are effective on enhancing the intranasal absorption of macromolecular drugs, very few papers focus on the changes of gel structure and rheology of the mucus caused by the mucoadhesive polymer, to what extent the interaction between the polymer and the mucus influences the release of the drugs including in the disease condition. Disease conditions can affect mucoadhesion due to their influence on either mucus production or ciliary movement, and then may result in undesired drug release. Thus, a good understanding of the nature of mucus in these diseases is imperative in designing a good nasal drug delivery system. Mucoadhesive capabilities of polymers should be studied under such disease conditions during the product development.
Mucoadhesive Polymers used in Nasal Drug Delivery | |  |
Cellulose Derivatives
There are many pharmaceutical grade derivatives of cellulose widely used in different administration routes. Several cellulose derivatives have proved to be effective on enhancing the intranasal absorption of drugs, including soluble cellulose derivatives such as hydroxypropyl methylcellulose, hydroxypropyl cellulose (HPC), methylcellulose (MC), and carboxymethyl cellulose (CMC), and insoluble cellulose derivatives such as ethylcellulose and microcrystalline cellulose (MCC).
Cellulose derivatives can markedly prolong the residence time of drugs in the nasal cavity due to their desirable mucoadhesive property. [32] Additionally, due to their high viscosity following hydration in the nasal cavity, the celluloses can sustain the release of drugs. [33] For these reasons, using celluloses as absorption enhancer can lead to improved intranasal absorption and increased bioavailability. Many references show that the celluloses are effective on increasing the intranasal bioavailability of small hydrophobic as well as hydrophilic macromolecular drugs [Table 1]. For example, administered nasally with CMC, apomorphine can obtain a relative bioavailability of 102% compared with subcutaneous injection in rabbits.[34] Another study reported that an absolute bioavailability up to 90.77% could be achieved for ketorolac tromethamine administered with MCC.[35] The peptide drugs, leuprolide and FD-4, when dosed with MCC/HPC through nasal route, reached an absolute bioavailability of 34.9% and 35.5% in rabbits, respectively. [36] | Table 1: Summary of some nasal drug delivery studies where cellulose derivatives were employed
Click here to view |
Sometimes, combination of the celluloses with other absorption enhancer would obtain the better effectiveness than using the polymer alone. [37] reported that the intranasal absolute bioavailability of ciprofloxacin in rabbits using MC and HEC alone as enhancer is only 18.2% and 19.46%, respectively. When combining with the Tween 80, the bioavailability increased to 22.35% and 25.39%, respectively. [39] In another study by on the intranasal delivery of dopamine, the combination of the HPC and azone leaded to an absolute bioavailability of almost 100%, while it was only 25% for using HPC alone. [38]
Polyacrylates
Polyacrylates have been investigated very frequently in many drug administration routes, like nasal drug delivery systems, due to their excellent mucoadhesive and gel-forming capability. Among the pharmaceutical polyacrylates, carbomers, and polycarbophil, which differ in the cross-linking condition and viscosity, are widely used in the nasal mucoadhesive drug delivery systems.[39]
Polyacrylates, capable of attaching to mucosal surfaces, can offer the prospects of prolonging the residence time of drugs at the sites of drug absorption, and ensure intimate contact between the formulation and membrane surface. Studies by Ugwoke et al. in rabbits reported that the use of Carbopol 971P in nasal dosage forms increases their residence time in the nasal cavity. The percentage of the formulations cleared from the nasal cavity at 3 hours was 24% for Carbopol 971P, while it was 70% for lactose. Sustained release of drugs can also be obtained by using polyacrylates in nasal formulation, which result in a more stable blood concentration-time curve. [Table 2] shows the use of polyacrylates in nasal drug delivery system. [34],[40] | Table 2: Summary of the studies on the use of polyacrylates in nasal drug delivery
Click here to view |
Another research by Ugwoke et al. showed that the Tmax of the Carbopol 971P-containing formulation of apomorphine was 52.21 minutes, which represented a 5-fold improvement compared with that of the lactose-containing formulation, while the Cmax of the Carbopol 971P-containing formulation was 330.2 ng/ml, lower than that of the lactose-containing formulation, which was 450.7 ng/ml. [34],[41]
Besides the mucoadhesion capability, polyacrylates may also temporarily open the tight junctions between the epithelial cells during the swelling progress in the nasal cavity and improve the paracellular absorption of drugs. [42]
An absolute bioavailability of 14.4% in rabbits was reported for intranasal insulin formulation containing Carbopol 974P.
Callens and Remon reported that the effect of Carbopol on the mucosa is negligible and reversible, no change of the epithelium barrier was observed even after a 4-week administration of Carbopol-based powder formulation in rabbits.
Starch
The starch is one of the most widely used mucoadhesive carrier for nasal drug delivery, which has been reported to be effective on improving the absorption of both small hydrophobic drugs and hydrophilic macromolecular drugs [Table 3]. Maize starch is the most preferred class for pharmaceutical purpose, among which the drum-dried waxy maize starch, due to its better bioadhesive property, has been considered as the best one compared with starch processed through other methods. [43] | Table 3: Summary of some nasal drug delivery studies where starch and other carbohydrates were employed
Click here to view |
Starch can be used as nasal drug carriers in the form of powder microspheres nanoparticles [Table 3] among which the degradable starch microspheres (DSM), also known as SpherexR, is the most widely used and also the first example of mucoadhesive microparticulate nasal delivery system. These microspheres are prepared by an emulsion polymerization technique, in which the starch is cross-linked with epichlorohydrin and can incorporate molecules weighting less than 30 kDa [44] have observed that the half-life of clearance for DSM was prolonged to 240 minutes as compared with 15 minutes for the liquid and powder control formulations.[45]
Chitosan
Chitosan [2-amino-2-deoxy-(1→4)-β-d-glucopyranan] is a linear cationic polysaccharide which is obtained by a process of deacetylation from chitin, an abundant structural polysaccharide in shells of crustacea, such as lobsters, shrimps, and crabs. Due to the NH 2 groups resultant from the deacetylation process, chitosan is insoluble at neutral and alkaline pH. However, it can form water-soluble salts with inorganic and organic acids including glutamic acid, hydrochloric acid, lactic acid, and acetic acid. Toxicity tests have revealed that the LD50 of chitosan in mice exceeds 16 g/kg (Paul and Garside, 2000). Because of its low cost, biodegradability, and biocompatibility, chitosan has been increasingly applied as pharmaceutical excipients in oral, ocular, nasal, implant, parenteral, and transdermal drug delivery.[46]
Chitosan and its derivatives have been shown to be active in enhancing the intranasal drug absorption due to their excellent mucoadhesive properties. It was also confirmed that coating micro- and nanoparticulates with chitosan could improve drug adsorption to mucosal surfaces. [47] [Table 4] shows various chitosan derivatives used in nasal drug delivery system. | Table 4: Summary of the recent nasal drug delivery studies where chitosan derivatives were employed as absorption enhancer
Click here to view |
Soane et al. reported that chitosan microspheres and solutions resulted in three- and eight-fold longer clearance half-lives compared with sodium pertechnetate solution in sheep nasal cavity, respectively.[6],[48] In addition, many studies have proved that chitosan and its derivatives could transiently open the tight junctions between the cells and lead to the paracellular transport of drugs.[49] and Chung et al. have observed interpenetration of thermo-sensitive gels of insulin in nasal delivery by cross linking of chitosan. The preparation shows sustained release of insulin and improved pharmacological efficiency.[50]
Chemical and biological properties of chitosan, such as mucoadhesion and ability in enhancing nasal absorption, are determined by the types of derivatives, degree of deacetylation, and molecular weight, because chitosan is only soluble in acidic environment in which the amino groups at the C-2 position are protonated. At neutral pH, most chitosan molecules will lose their charge and precipitate from solution. [50]
Recent studies have shown that only protonated, soluble chitosan can trigger the opening of tight junctions and thereby facilitate the paracellular transport of hydrophilic mannitol.[51]
To improve the poor water solubility of chitosan, some derivatives were synthesized, such as trimethyl chitosan. [52]
Thanou et al. reported that the trimethyl chitosan was soluble and effective on enhancing intranasal absorption even at neutral pH. [53] N-trimethyl chitosan hydrochlorides are more mucoadhesive than unmodified chitosans and show a higher bioavailability in vivo compared with the unmodified chitosans. [54]
Mei et al. reported that the permeation-enhancing effect of chitosan increased with increasing molecular weight up to Mw 100.[55]
Tengamnuay et al. suggested that chitosans should differ in their molecular weight by at least two-fold in order to have a clearly differentiating effect on the nasal absorption enhancement of a kyotorphin analogue.[22]
On the contrary, Zaki et al. found that there is no significant difference between the constants of intranasal absorption for metoclopramide HCl administered with chitosan high weight (600 kDa) and low weight (150 kDa) even though they differ in molecular weight by four-fold.
Due to the positive charge of chitosan in a weak acidic environment, it can also be applied to deliver the negatively charged DNA through nasal mucosa and protect them from nuclease degradation. [35]
Compared with viral vectors, this alternative vector markedly reduced the safety risks that meanwhile result in high transfectability. Recently, many studies show that nasal immunization with chitosan plus inactive vaccine is a potentially effective, easily administered form of vaccination. [56] Bordetella pertussis filamentous hemagglutinin and recombinant pertussis toxin have shown to induce very strong systemic and mucosal immune reactions against the antigens when intranasally administrated with chitosan. [57]
Read et al. confirmed that the standard inactivated trivalent influenza vaccine administered intranasally in combination with chitosan glutamate (0.5%, w/w) could induce both systemic and local immune responses, and the results were not statistically different from those obtained following administration of the commercial influenza vaccine by the intramuscular route.
Bacon et al. have reported that chitosan solutions are able to enhance both the mucosal and systemic immune responses against influenza virus vaccines. Only in mice which received chitosan/vaccine formulation intranasally, high IgA titers in nasal washings could be found. This was not observed in mice receiving the antigen through subcutaneous injection. [58]
Conclusion | |  |
With advantages such as mucoadhesion, an increase in the residence time of the polymer, penetration enhancement, and enzymatic inhibition, mucoadhesive polymers will undoubtedly be utilized for the nasal delivery of a wide variety of therapeutic compounds. This class of polymers has enormous potential for the delivery of therapeutic macromolecules, genes, and vaccines. Unfortunately, only a few studies have been conducted with new generation mucoadhesive polymers for nasal drug delivery, and very few papers focus on the changes of structure and rheology of the mucus caused by the mucoadhesive polymer, to what extent the interaction between the polymer and the mucus influences the release of the drugs including in the disease condition. With recent advancements in the fields of biotechnology and cytoadhesion, the authors believe that there will be both academic and industrial efforts to explore this new area of nasal drug delivery, and it might not be too far-fetched to envisage more and more nasal products that employ mucoadhesive polymers. The authors believe that there will be both academic and industrial efforts to explore this new area of nasal drug delivery, and more nasal products that employs mucoadhesive polymers.[Figure 3]
References | |  |
1. | Asane GS, Nirmal SA, Rasal KB, Naik AA, Mahadik MS, Madhusudan Rao YM. Polymers for mucoadhesive drug delivery system: A current status. Drug Dev Ind Pharm 2008;34:1246-66.  |
2. | Harris AS. Review: Clinical opportunities provided by the nasal administration of peptides. J Drug Targeting 1993;1:101-16.  |
3. | Chien YW, Chang SF. In: Nasal Systemic Drug Delivery. New York: Dekker; 1989. p.1-26.  |
4. | Limzerwala RB, Paradkar AR, Pawar AP, Mahadik KR. Nasal drug absorption; Review article. Indian Drug 1995;33:243-50.  |
5. | Lisbeth I. Nasal drug delivery- possibilities problems and solutions. J Control Release 2003;87:187-98.  |
6. | Soane RJ, Hinchcliffe M, Davis SS, Illum L. Clearance characteristics of chitosan based formulations in the sheep nasal cavity. Int J Pharm 2001;217:183-91.  [PUBMED] [FULLTEXT] |
7. | Ugwoke MI, Kaufmann G, Verbeke N, Kinget R. Intranasal bioavailability of apomorphine from carboxymethylcellulose-based drug delivery systems. Int J Pharm 2000;202:125-31.  [PUBMED] [FULLTEXT] |
8. | Tortora GJ, Grabowski SR. Principles of Anatomy and Physiology. 17 th ed. Harper Collins College Publishers; 2001.  |
9. | Nielsan HW, Bichgaard E, Twile B. Intra nasal administration of different liquid formulations of bumentanide to rabbit. Int J Pharm 2000;204:35-41.  |
10. | Joshi M, Misra A. Dry powder inhalation of liposomal Ketotifen fumarate; formulation and characterization. Int J Pharm 2001;223:15-27.  [PUBMED] [FULLTEXT] |
11. | Kublik H, Vidgren MT. Nasal delivery systems and their effect on deposition and absorption. Adv Drug Deliv Rev 1998;29:157-77.  |
12. | Castellanos J, Zia H, Rhodes CT. Mucoadhesive drug delivery systems. Drug Dev Ind Pharm 1993;19:143-94.  |
13. | Lee WA, Narog BA, Patapoff TW, Wang YJ. Intranasal bioavailability of insulin powder formulations: Effect of permeation enhancer-to-protein ratio. J Pharm Sci 1991;80:725-9.  [PUBMED] |
14. | Garmise RJ, Staats HF, Hickey AJ. Novel dry powder preparations of whole inactivated influenza virus for nasal vaccination. AAPS Pharm Sci Tech 2007;8:E81.  |
15. | Wadell C. Nasal Drug Delivery - In vitro studies on factors influencing permeability and implication on absorption. Drug Metabolism. Revi. 1999;7:197-206  |
16. | Wang X, Chi N, Tang X. Preparation of estradiol chitosan nanoparticles for improving nasal absorption and brain targeting. Eur J Pharm Biopharm 2008;70:735-40.  [PUBMED] [FULLTEXT] |
17. | Miyamoto M, Natsume H, Iwata S, Ohtake K, Yamaguchi M, Kobayashi D, et al. Improved nasal absorption of drugs using poly-l-arginine: Effects of concentration and molecular weight of poly-l-arginine on the nasal absorption of fluorescein isothiocyanate-dextran in rats. Eur J Pharm Biopharm 2001;52:21-30.  [PUBMED] [FULLTEXT] |
18. | Calvo P, Remunan-Lopez C, Alonso MJ. Enhancement of nasal absorption of insulin using chitosan nanoparticles. Pharm Res 1999;16:1576-81.  |
19. | Jain AK, Khar RK, Ahmed FJ, Diwan PV. Effective insulin delivery using starch nanoparticles as a potential trans-nasal mucoadhesive carrier. Eur J Pharm Biopharm 2008;69:426-35.  [PUBMED] [FULLTEXT] |
20. | Donovan MD, Huang Y. Large molecule and particulate uptake in the nasal cavity: The effect of size on nasal absorption. Adv Drug Deliv Rev 1998;29:147-55.  |
21. | Amidi M, Romeijn SG, Borchard G, Junginger HE, Hennink WE, Jiskoot W. Preparation and characterization of protein-loaded N-trimethyl chitosan nanoparticles as nasal delivery system. J Contr Rel 2006;111:107-16.  |
22. | Tengamnuay P, Sahamethapat A, Sailasuta A, Mitra AK. Chitosans as nasal absorption enhancers of peptides: Comparison between free amine chitosans and soluble salts. Int J Pharm 2000;197:53-67.  [PUBMED] [FULLTEXT] |
23. | Csaba N, Garcia-Fuentes M, Alonso MJ. Nanoparticles for nasal vaccination. Adv Drug Deliv Rev 2009;61:140-57.  [PUBMED] [FULLTEXT] |
24. | Pereswetoff-Morath L. Microspheres as nasal drug delivery systems. Adv Drug Deliv Rev 1998;29:185-94.  [PUBMED] [FULLTEXT] |
25. | Mishra PR, Namdeo A, Jain S, Jain NK. Hydrogel as drugdelivery system. Indian Drugs 1998;33:181-6.  |
26. | Kawasaki N, Ohkura R, Miyazaki S. Thermally reversible xyloglucan gets as vehicles for oral drug delivery. Int J Pharm 1999;181:227-34.  |
27. | Shahiwala A, Misra A. Nasal delivery of levonorgestrel for contraception: An experimental study in rats. Fertil Steril 2004;81:893-8.  [PUBMED] [FULLTEXT] |
28. | Suzuki Y, Makino Y. Mucosal drug delivery using cellulose derivatives as a functional polymer. J Control Release 1999;62:101-7.  [PUBMED] [FULLTEXT] |
29. | Ahuja A, Khar RK, Ali J. Mucoadhesive drug delivery systems. Drug Dev Ind Pharm 1997;23:489-515.  |
30. | Luessen HL, De-Leeuw BJ, Langemeyer M, De-Boer AG, Verhoef JC, Unginger HE. Mucoadhesive polymers in peroral peptide drug delivery. IV. Carbomer and chitosan improve the intestinal absorption of the peptide drug buserelin in vivo. Pharm Res 1996;13:1668-72.  |
31. | Jabbal-Gill I, Fisher AN, Farraj N, Pitt CG, Davis SS, Illum L. Intranasal absorption of granulocyte-colony stimulating factor (G-CSF) from powder formulations, in sheep. Eur J Pharm Sci 1998;6:1-10.  |
32. | Zaki NM, Awada GA, Mortadaa ND, Abd ElHadyb SS. Enhanced bioavailability of metoclopramide HCl by intranasal administration of mucoadhesive in situ gel with modulated rheological and mucociliary transport properties. Eur J Pharm Sci 2007;32:296-307.  |
33. | Wang X, Chi N, Tang X. Preparation of estradiol chitosan nanoparticles for improving nasal absorption and brain targeting. Eur J Pharm Biopharm 2008;70:735-40.  [PUBMED] [FULLTEXT] |
34. | Ugwoke MI, Sam E, Van Den Mooter G, Verbeke N, Kinget R. Bioavailability of apomorphine following intranasal administration of mucoadhesive drug delivery systems in rabbits. Eur J Pharm Sci 1999;9:213-9.  [PUBMED] [FULLTEXT] |
35. | Quadir M, Zia H, Needham TE. Toxicological implications of nasal formulations. Drug Del 1999;6:227-42.  |
36. | Tas C, Ozkan CK, Savaser A, Ozkan Y, Tasdemir U, Altunay H. Nasal absorption of metoclopramide from different Carbopol 981 based formulations: In vitro, ex vivo and in vivo evaluation. Eur J Pharm Biopharm 2006;64:246-54.  [PUBMED] [FULLTEXT] |
37. | Paulsson M. Controlled Release Gel Formulation for Mucosal Drug Delivery. ACTA Universitatis Upsaliensin Uppasla 2001;7:9-21  |
38. | Ikeda K, Murata K, Kobayashi M, Noda K. Enhancement of bioavailability of dopamine via nasal route in beagle dogs. Chem Pharm Bull 1992;40:2155-8.  [PUBMED] |
39. | Teijeiro-Osorio D, Remunan-Lopez C, Alonso MJ. Chitosan/cyclodextrin nanoparticles can efficiently transfect the airway epithelium in vitro. Eur J Pharm Biopharm 2009;71:257-63.  |
40. | Vidgren P, Vidgren M, Arppe J, Hakuli T, Laine E, Paronen P. In vitro evaluation of spray-dried mucoadhesive microspheres for nasal administration. Drug Dev Ind Pharm 1992;18:581-97.  |
41. | Smart JD. The basics and underlying mechanisms of mucoadhesion. Adv Drug Deliv Rev 2005;57:1556-68.  [PUBMED] [FULLTEXT] |
42. | Callens C, Remon JP. Evaluation of starchmaltodextrin-Carbopol 974P mixtures for the nasal delivery of insulin in rabbits. J Contr Rel 2000;66:215-20.  |
43. | Callens C, Pringels E, Remon JP. Influence of multiple nasal administrations of bioadhesive powders on the insulin bioavailability. Int J Pharm 2003;250:415-22.  [PUBMED] [FULLTEXT] |
44. | Quadir M, Zia H, Needham TE. Development and evaluation of nasal formulations of ketorolac. Drug Deliv 2000;7:223-9.  [PUBMED] [FULLTEXT] |
45. | Illum L, Jorgensen H, Bisgaard H, Krogsgaard O, Rossing N. Bioadhesive microspheres as a potential nasal drug delivery system. Int J Pharm 1987;39:189-99.  |
46. | Illum L. Nasal drug delivery: New developments and strategies. Drug Discov Today 2002;7:1184-9.  [PUBMED] [FULLTEXT] |
47. | Cui F, Qian F, Yin C. Preparation and characterization of mucoadhesive polymer-coated nanoparticles. Int J Pharm 2006;316:154-61.  [PUBMED] [FULLTEXT] |
48. | Sriamornsak P, Wattanakorn N, Nunthanid J, Puttipipatkhachorn S. Mucoadhesion of pectin as evidence by wettability and chain interpenetration. Carbohydr. Polym 2008;74:458-67.  |
49. | Artursson P, Lindmark T, Davis SS, Illum L. Effect of chitosan on the permeability of monolayers of intestinal epithelial cells (Caco-2). Pharm Res 1994;11:1358-61.  [PUBMED] [FULLTEXT] |
50. | Chung T, Liu D, Yang J. Effects of interpenetration of thermo-sensitive gels by crosslinking of chitosan on nasal delivery of insulin: In vitro characterization and in vivo study. Carbohydrate Polymers 2010;82:316-22.  |
51. | Issa MM, Koping-Hoggard M, Artursson P. Chitosan and the mucosal delivery of biotechnology drugs. Drug Discov Today 2005;2:1-6.  |
52. | Kotze AF, Luesen HL, De Boer AG, Verhoef JC, Junginger HE. Chitosan for enhanced intestinal permeability: Prospects for derivatives soluble in neutral and basic environments. Eur J Pharm Sci 1999;7:145-51.  |
53. | Thanou M, Verhoef JC, Verheijden JH, Junginger HE. Intestinal absorption of octeriotide: N-trimethyl chitosan chloride (TMC) ameliorates the permeability and absorption properties of the somatostatin analogue in vitro and in vivo. J Pharm Sci 2000;89:951-7.  [PUBMED] [FULLTEXT] |
54. | Lai WF, Lin MC. Nucleic acid delivery with chitosan and its derivatives. J Control Release 2009;134:158-68.  [PUBMED] [FULLTEXT] |
55. | Mei D, Mao S, Sun W, Wang Y, Kissel T. Effect of chitosan structure properties and molecular weight on the intranasal absorption of tetramethylpyrazine phosphate in rats. Eur J Pharm Biopharm 2008;70:874-81.  [PUBMED] [FULLTEXT] |
56. | Borchard G. Chitosans for gene delivery. Adv Drug Deliv Rev 2001;52:145-50.  [PUBMED] [FULLTEXT] |
57. | VanderLubben IM, Kersten G, Fretz MM, Beuvery C, Junginger HE. Chitosan microparticles for mucosal vaccination against diphtheria oral and nasal efficacy studies in mice. 2003;21:1400-8.  |
58. | Bacon A, Makin J, Sizer P J, Jabbal-Gill I, Hinchcliffe M, Illum L, et al. Carbohydrate biopolymers enhance antibody responses to mucosally delivered vaccine antigens. Infect Immun 2000;68:5764-70.  |
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]
This article has been cited by | 1 |
Recent advances in respiratory immunization: A focus on COVID-19 vaccines |
|
| Xiyue He, Xiaoyan Chen, Hairui Wang, Guangsheng Du, Xun Sun | | Journal of Controlled Release. 2023; 355: 655 | | [Pubmed] | [DOI] | | 2 |
Mucoadhesive drug delivery systems: a promising noninvasive approach to bioavailability enhancement. Part II: formulation considerations |
|
| Radha Kulkarni, Suraj Fanse, Diane J. Burgess | | Expert Opinion on Drug Delivery. 2023; : 1 | | [Pubmed] | [DOI] | | 3 |
A Supine Position and Dual-Dose Applications Enhance Spray Dosing to the Posterior Nose: Paving the Way for Mucosal Immunization |
|
| Amr Seifelnasr, Mohamed Talaat, Pranav Ramaswamy, Xiuhua April Si, Jinxiang Xi | | Pharmaceutics. 2023; 15(2): 359 | | [Pubmed] | [DOI] | | 4 |
Polymeric Nanoparticles for Inhaled Vaccines |
|
| Nusaiba K. Al-Nemrawi, Ruba S. Darweesh, Lubna A. Al-shriem, Farah S. Al-Qawasmi, Sereen O. Emran, Areej S. Khafajah, Muna A. Abu-Dalo | | Polymers. 2022; 14(20): 4450 | | [Pubmed] | [DOI] | | 5 |
Pharmacokinetic Study of Mucoadhesive Itopride Hydrochloride In Situ Nasal Gel Formulations in a Comparative In Vivo Study and Histopathological Safety Evaluation |
|
| Maha A. Marzouk, Dina A. Osman, Amany I. Abd El-Fattah, Reem A. Aldeeb | | Scientia Pharmaceutica. 2022; 90(1): 8 | | [Pubmed] | [DOI] | | 6 |
Protective efficacy of intranasal inactivated pseudorabies vaccine is improved by combination adjuvant in mice |
|
| Tao Hua, Chen Chang, Xuehua Zhang, Yuqing Huang, Haiyan Wang, Daohua Zhang, Bo Tang | | Frontiers in Microbiology. 2022; 13 | | [Pubmed] | [DOI] | | 7 |
Nose-to-Brain: The Next Step for Stem Cell and Biomaterial Therapy in Neurological Disorders |
|
| Natalia Villar-Gómez, Doddy Denise Ojeda-Hernandez, Eneritz López-Muguruza, Silvia García-Flores, Natalia Bonel-García, María Soledad Benito-Martín, Belen Selma-Calvo, Alejandro Arturo Canales-Aguirre, Juan Carlos Mateos-Díaz, Paloma Montero-Escribano, Jordi A. Matias-Guiu, Jorge Matías-Guiu, Ulises Gómez-Pinedo | | Cells. 2022; 11(19): 3095 | | [Pubmed] | [DOI] | | 8 |
Non-Cellular Layers of the Respiratory Tract: Protection against Pathogens and Target for Drug Delivery |
|
| Eleonore Fröhlich | | Pharmaceutics. 2022; 14(5): 992 | | [Pubmed] | [DOI] | | 9 |
Development of Nasal Vaccines and the Associated Challenges |
|
| Xuanxuan Nian, Jiayou Zhang, Shihe Huang, Kai Duan, Xinguo Li, Xiaoming Yang | | Pharmaceutics. 2022; 14(10): 1983 | | [Pubmed] | [DOI] | | 10 |
Immunological Assessment of Chitosan or Trimethyl Chitosan-Coated PLGA Nanospheres Containing Fusion Antigen as the Novel Vaccine Candidates Against Tuberculosis |
|
| Sirwan Zare, Mona Kabiri, Yousef Amini, Adel Najafi, Fatemeh Mohammadpour, Seyed Hasan Ayati, Amin Reza Nikpoor, Mohsen Tafaghodi | | AAPS PharmSciTech. 2022; 23(1) | | [Pubmed] | [DOI] | | 11 |
Recent advances on drug delivery applications of mucopenetrative/mucoadhesive particles: A review |
|
| Vishal Puri, Vishav Prabhjot Kaur, Arti Singh, Charan Singh | | Journal of Drug Delivery Science and Technology. 2022; : 103712 | | [Pubmed] | [DOI] | | 12 |
Development and optimization of candesartan cilexetil nasal gel for accentuated intranasal delivery using central composite design |
|
| Abhishek Sharma, Rakesh Thakur, Rajiv Sharma | | Materials Today: Proceedings. 2022; | | [Pubmed] | [DOI] | | 13 |
Mucosa-interfacing electronics |
|
| Kewang Nan, Vivian R. Feig, Binbin Ying, Julia G. Howarth, Ziliang Kang, Yiyuan Yang, Giovanni Traverso | | Nature Reviews Materials. 2022; | | [Pubmed] | [DOI] | | 14 |
In vitro & In vivo evaluations of PLGA nanoparticle based combinatorial drug therapy for Baclofen and Lamotrigine for neuropathic pain management |
|
| Kuldeep Nigam, Atinderpal Kaur, Amit Tyagi, Kailash Manda, Nidhi Goswami, Md Nematullah, Farah Khan, Reema Gabrani, Pammi Gauba, Shweta Dang | | Journal of Microencapsulation. 2022; : 1 | | [Pubmed] | [DOI] | | 15 |
Targeting neuroinflammation by intranasal delivery of nanoparticles in neurological diseases: a comprehensive review |
|
| Fatemeh Moradi, Nasrin Dashti | | Naunyn-Schmiedeberg's Archives of Pharmacology. 2022; | | [Pubmed] | [DOI] | | 16 |
Recent Advances in Mucoadhesive Interface Materials, Mucoadhesion Characterization, and Technologies |
|
| Ilker S. Bayer | | Advanced Materials Interfaces. 2022; : 2200211 | | [Pubmed] | [DOI] | | 17 |
Hyaluronate Spreading Validates Mucin-Agarose Analogs as Test Systems to Replace Porcine Nasal Mucosa Explants – an Experimental and Theoretical Investigation |
|
| Lena Marie Spindler, Stefania Serpetsi, Johannes Flamm, Andreas Feuerhake, Lisa Böhler, Martin Pravda, Kirsten Borchers, Günter E.M. Tovar, Katharina Schindowski, Carmen Gruber-Traub | | Colloids and Surfaces B: Biointerfaces. 2022; : 112689 | | [Pubmed] | [DOI] | | 18 |
Spray dried powders for nasal delivery: Process and formulation considerations |
|
| Patrícia Henriques, Ana Fortuna, Slavomíra Doktorovová | | European Journal of Pharmaceutics and Biopharmaceutics. 2022; | | [Pubmed] | [DOI] | | 19 |
Novel development of cationic surfactant-based mucoadhesive nanovaccine for direct immersion vaccination against Francisella noatunensis subsp. orientalis in red tilapia (Oreochromis sp.) |
|
| Patcharapong Thangsunan, Sirikorn Kitiyodom, Prapansak Srisapoome, Nopadon Pirarat, Teerapong Yata, Pattanapong Thangsunan, Suwimon Boonrungsiman, Anurak Bunnoy, Channarong Rodkhum | | Fish & Shellfish Immunology. 2022; | | [Pubmed] | [DOI] | | 20 |
Nitric oxide and viral infection: Recent developments in antiviral therapies and platforms |
|
| Mark R. Garren,Morgan Ashcraft,Yun Qian,Megan Douglass,Elizabeth J. Brisbois,Hitesh Handa | | Applied Materials Today. 2021; 22: 100887 | | [Pubmed] | [DOI] | | 21 |
Challenges of peptide and protein drug delivery by oral route: Current strategies to improve the bioavailability |
|
| Saurabh Verma,Umesh K. Goand,Athar Husain,Roshan A. Katekar,Richa Garg,Jiaur R. Gayen | | Drug Development Research. 2021; | | [Pubmed] | [DOI] | | 22 |
Lipid-Based Nanocarriers via Nose-to-Brain Pathway for Central Nervous System Disorders |
|
| Thuy Trang Nguyen, Thi Thuy Dung Nguyen, Nguyen-Minh-An Tran, Giau Van Vo | | Neurochemical Research. 2021; | | [Pubmed] | [DOI] | | 23 |
Deciphering the role of nanoparticles for management of bacterial meningitis: an update on recent studies |
|
| Neelam Sharma,Ishrat Zahoor,Monika Sachdeva,Vetriselvan Subramaniyan,Shivkanya Fuloria,Neeraj Kumar Fuloria,Tanveer Naved,Saurabh Bhatia,Ahmed Al-Harrasi,Lotfi Aleya,Simona Bungau,Tapan Behl,Sukhbir Singh | | Environmental Science and Pollution Research. 2021; | | [Pubmed] | [DOI] | | 24 |
Progress in nasal drug delivery systems |
|
| Flavia Laffleur,Bettina Bauer | | International Journal of Pharmaceutics. 2021; 607: 120994 | | [Pubmed] | [DOI] | | 25 |
Intranasal vaccine: factors to consider in research and development |
|
| Haiyue Xu,Lucy Cai,Stephanie Hufnagel,Zhengrong Cui | | International Journal of Pharmaceutics. 2021; : 121180 | | [Pubmed] | [DOI] | | 26 |
Advancements in the Pharmaceutical Applications of Probiotics: Dosage Forms and Formulation Technology |
|
| Kshitis Chandra Baral, Rajiv Bajracharya, Sang Hoon Lee, Hyo-Kyung Han | | International Journal of Nanomedicine. 2021; Volume 16: 7535 | | [Pubmed] | [DOI] | | 27 |
PLGA Nanoparticles for Nose to Brain Delivery of Clonazepam: Formulation, Optimization by 32 Factorial Design, In Vitro and In Vivo Evaluation |
|
| Pranav Shah, Jayant Sarolia, Bhavin Vyas, Priti Wagh, Kaul Ankur, Mishra Anil Kumar | | Current Drug Delivery. 2021; 18(6): 805 | | [Pubmed] | [DOI] | | 28 |
Lamotrigine loaded PLGA nanoparticles intended for direct nose to brain delivery in epilepsy: pharmacokinetic, pharmacodynamic and scintigraphy study |
|
| Pranav Shah,Priya Dubey,Bhavin Vyas,Ankur Kaul,Anil Kumar Mishra,Dimple Chopra,Priya Patel | | Artificial Cells, Nanomedicine, and Biotechnology. 2021; 49(1): 511 | | [Pubmed] | [DOI] | | 29 |
Nanotechnologies for intranasal drug delivery: an update of literature |
|
| Rosamaria Lombardo,Teresa Musumeci,Claudia Carbone,Rosario Pignatello | | Pharmaceutical Development and Technology. 2021; : 1 | | [Pubmed] | [DOI] | | 30 |
Biomaterials for Drugs Nose–Brain Transport: A New Therapeutic Approach for Neurological Diseases |
|
| Roberta Cassano,Camilla Servidio,Sonia Trombino | | Materials. 2021; 14(7): 1802 | | [Pubmed] | [DOI] | | 31 |
Quality by Design Approach for the Development of Liposome Carrying Ghrelin for Intranasal Administration |
|
| Cecília de Barros,Norberto Aranha,Patrícia Severino,Eliana B. Souto,Aleksandra Zielinska,André Lopes,Alessandra Rios,Fernando Batain,Kessi Crescencio,Marco Chaud,Thais Alves | | Pharmaceutics. 2021; 13(5): 686 | | [Pubmed] | [DOI] | | 32 |
Low Acyl Gellan as an Excipient to Improve the Sprayability and Mucoadhesion of Iota Carrageenan in a Nasal Spray to Prevent Infection With SARS-CoV-2 |
|
| Thomas E. Robinson,Richard J. A. Moakes,Liam M. Grover | | Frontiers in Medical Technology. 2021; 3 | | [Pubmed] | [DOI] | | 33 |
Nose to Brain Drug Delivery System |
|
| Gayatri D Patil, Aditya R Nikam, Paresh A. Patil, Aakash D. Sonar | | Research Journal of Pharmaceutical Dosage Forms and Technology. 2021; : 335 | | [Pubmed] | [DOI] | | 34 |
A Comprehensive Review of Intranasal Insulin and Its Effect on the Cognitive Function of Diabetics |
|
| Mrunanjali Gaddam,Abhishek Singh,Nidhi Jain,Chaithanya Avanthika,Sharan Jhaveri,Ivonne De la Hoz,Sujana Sanka,Sri Rupa Goli | | Cureus. 2021; | | [Pubmed] | [DOI] | | 35 |
Cationic Nanostructures for Vaccines Design |
|
| Ana Maria Carmona-Ribeiro,Yunys Pérez-Betancourt | | Biomimetics. 2020; 5(3): 32 | | [Pubmed] | [DOI] | | 36 |
Mucoadhesive Properties of Gellan and Its Modified Derivatives |
|
| Gul’nur Tatykhanova,Vladimir Aseyev,Sarkyt E. Kudaibergenov | | Reviews and Advances in Chemistry. 2020; 10(3-4): 140 | | [Pubmed] | [DOI] | | 37 |
Mucoadhesive formulations: innovations, merits, drawbacks, and future outlook |
|
| Amresh Kumar,Pradeep Kumar Naik,Deepak Pradhan,Goutam Ghosh,Goutam Rath | | Pharmaceutical Development and Technology. 2020; : 1 | | [Pubmed] | [DOI] | | 38 |
Chitosan Nanoparticle Based Mucosal Vaccines Delivered Against Infectious Diseases of Poultry and Pigs |
|
| Sankar Renu,Gourapura J. Renukaradhya | | Frontiers in Bioengineering and Biotechnology. 2020; 8 | | [Pubmed] | [DOI] | | 39 |
Design and Application in Delivery System of Intranasal Antidepressants |
|
| Jingying Xu,Jiangang Tao,Jidong Wang | | Frontiers in Bioengineering and Biotechnology. 2020; 8 | | [Pubmed] | [DOI] | | 40 |
The uses of resveratrol for neurological diseases treatment and insights for nanotechnology based-drug delivery systems |
|
| Bruno Fonseca-Santos,Marlus Chorilli | | International Journal of Pharmaceutics. 2020; 589: 119832 | | [Pubmed] | [DOI] | | 41 |
Nasal Mucoadhesive Microspheres of Lercanidipine with Improved Systemic Bioavailability and Antihypertensive Activity |
|
| Sarwar Beg,Mahfoozur Rahman,Sunil K. Panda,Khalid S. Alharbi,Nabil K. Alruwaili,Nabil K. Ameeduzzafar,Pradeep K. Singh,Monica Thappa,Bhupinder Singh | | Journal of Pharmaceutical Innovation. 2020; | | [Pubmed] | [DOI] | | 42 |
A gellan gum derivative as in-situ gelling cationic polymer for nasal drug delivery |
|
| Max Jelkmann,Christina Leichner,Sergey Zaichik,Flavia Laffleur,Andreas Bernkop-Schnürch | | International Journal of Biological Macromolecules. 2020; | | [Pubmed] | [DOI] | | 43 |
Nose-to-brain delivery of lamotrigine-loaded PLGA nanoparticles |
|
| Kuldeep Nigam,Atinderpal Kaur,Amit Tyagi,Md Nematullah,Farah Khan,Reema Gabrani,Shweta Dang | | Drug Delivery and Translational Research. 2019; | | [Pubmed] | [DOI] | | 44 |
Chlorpheniramine maleate containing chitosan-based nanoparticle-loaded thermosensitive in situ gel for management in allergic rhinitis |
|
| Manish Kumar,Pooja Upadhayay,Ravi Shankar,Monika Joshi,Shailendra Bhatt,Anuj Malik | | Drug Delivery and Translational Research. 2019; | | [Pubmed] | [DOI] | | 45 |
Intranasal Zotepine Nanosuspension: intended for improved brain distribution in rats |
|
| Sravanthi Reddy Pailla,Sreekanth Talluri,Nagarjun Rangaraj,Ramdas Ramavath,Veerabhadra Swamy Challa,Nandkumar Doijad,Sunitha Sampathi | | DARU Journal of Pharmaceutical Sciences. 2019; | | [Pubmed] | [DOI] | | 46 |
In situ thermo-co-electroresponsive mucogel for controlled release of bioactive agent |
|
| Olufemi D. Akilo,Pradeep Kumar,Yahya E. Choonara,Lisa C. du Toit,Priyamvada Pradeep,Girish Modi,Viness Pillay | | International Journal of Pharmaceutics. 2019; 559: 255 | | [Pubmed] | [DOI] | | 47 |
How to characterize a nasal product. The state of the art of in vitro and ex vivo specific methods |
|
| Laurent Salade,Nathalie Wauthoz,Jonathan Goole,Karim Amighi | | International Journal of Pharmaceutics. 2019; 561: 47 | | [Pubmed] | [DOI] | | 48 |
Spray-dried alginate microparticles for potential intranasal delivery of ropinirole hydrochloride: development, characterization and histopathological evaluation |
|
| Nozad Hussein,Huner Omer,Ava Ismael,Mohamed Albed Alhnan,Abdelbary Elhissi,Waqar Ahmed | | Pharmaceutical Development and Technology. 2019; : 1 | | [Pubmed] | [DOI] | | 49 |
Mucoadhesive Hydrogel Nanoparticles as Smart Biomedical Drug Delivery System |
|
| Nemany Hanafy,Stefano Leporatti,Maged El-Kemary | | Applied Sciences. 2019; 9(5): 825 | | [Pubmed] | [DOI] | | 50 |
D-cycloserine nasal formulation development for anxiety disorders by using polymeric gels |
|
| Yeonoh Shin,Rutika Kokate,Vilas Desai,Alok Bhushan,Gagan Kaushal | | Drug Discoveries & Therapeutics. 2018; 12(3): 142 | | [Pubmed] | [DOI] | | 51 |
Nasal patches containing naphazoline for management of nasal impairments |
|
| Flavia Laffleur,Benedikt Strasdat | | Journal of Drug Delivery Science and Technology. 2018; | | [Pubmed] | [DOI] | | 52 |
Overview of intranasally delivered peptides: key considerations for pharmaceutical development |
|
| Wisam Al Bakri,Maureen D. Donovan,Maria Cueto,Yunhui Wu,Chinedu Orekie,Zhen Yang | | Expert Opinion on Drug Delivery. 2018; 15(10): 991 | | [Pubmed] | [DOI] | | 53 |
Influence of Drug-Carrier Polymers on Alpha-Synucleinopathies: A Neglected Aspect in New Therapies Development |
|
| C. Tonda-Turo,M. Herva,V. Chiono,G. Ciardelli,M. G. Spillantini | | BioMed Research International. 2018; 2018: 1 | | [Pubmed] | [DOI] | | 54 |
Baclofen-Loaded Poly (d,l-Lactide-Co-Glycolic Acid) Nanoparticles for Neuropathic Pain Management: In Vitro and In Vivo Evaluation |
|
| Kuldeep Nigam,Atinderpal Kaur,Amit Tyagi,Kailash Manda,Reema Gabrani,Shweta Dang | | Rejuvenation Research. 2018; | | [Pubmed] | [DOI] | | 55 |
In Vitro Assessment of Nasal Insufflation of Comminuted Drug Products Designed as Abuse Deterrent Using the Vertical Diffusion Cell |
|
| Heather Boyce,Dan Smith,Steve Byrn,Bhawana Saluja,Wen Qu,Vadim J. Gurvich,Stephen W. Hoag | | AAPS PharmSciTech. 2018; 19(4): 1744 | | [Pubmed] | [DOI] | | 56 |
Lamotrigine Lipid Nanoparticles for Effective Treatment of Epilepsy: a Focus on Brain Targeting via Nasal Route |
|
| Puja K. Gangurde,Navya Ajitkumar B.,Lalit Kumar | | Journal of Pharmaceutical Innovation. 2018; | | [Pubmed] | [DOI] | | 57 |
Development of novel bioadhesive granisetron hydrochloride spanlastic gel and insert for brain targeting and study their effects on rats |
|
| Rehab Abdelmonem,Mohamed el Nabarawi,Alshaimaa Attia | | Drug Delivery. 2018; 25(1): 70 | | [Pubmed] | [DOI] | | 58 |
Montelukast nasal spray: formulation development and in vitro evaluation |
|
| Thunyaporn Jullaphant,Titpawan Nakpeng,Teerapol Srichana | | Pharmaceutical Development and Technology. 2018; : 1 | | [Pubmed] | [DOI] | | 59 |
Evaluation of intranasal delivery route of drug administration for brain targeting |
|
| Franciska Erdo,Luca Anna Bors,Dániel Farkas,Ágnes Bajza,Sveinbjörn Gizurarson | | Brain Research Bulletin. 2018; | | [Pubmed] | [DOI] | | 60 |
The potential of mucoadhesive polymer in enhancing efficacy of direct immersion vaccination against Flavobacterium columnare infection in tilapia |
|
| Sirikorn Kitiyodom,Somrudee Kaewmalun,Naiyaphat Nittayasut,Kunat Suktham,Suvimol Surassmo,Katawut Namdee,Channarong Rodkhum,Nopadon Pirarat,Teerapong Yata | | Fish & Shellfish Immunology. 2018; | | [Pubmed] | [DOI] | | 61 |
The wettability and swelling of selected mucoadhesive polymers in simulated saliva and vaginal fluids |
|
| M. Rojewska,M. Olejniczak-Rabinek,A. Bartkowiak,A. Snela,K. Prochaska,J. Lulek | | Colloids and Surfaces B: Biointerfaces. 2017; 156: 366 | | [Pubmed] | [DOI] | | 62 |
Formulation and Evaluation of Thermoreversible In Situ Nasal Gels Containing Mometasone Furoate for Allergic Rhinitis |
|
| Ebru Altuntas,Gülgün Yener | | AAPS PharmSciTech. 2017; | | [Pubmed] | [DOI] | | 63 |
Hydrogel nanoparticles and nanocomposites for nasal drug/vaccine delivery |
|
| Sara Salatin,Jaleh Barar,Mohammad Barzegar-Jalali,Khosro Adibkia,Mitra Alami Milani,Mitra Jelvehgari | | Archives of Pharmacal Research. 2016; | | [Pubmed] | [DOI] | | 64 |
Chitosan promotes aquaporin formation and inhibits mucociliary differentiation of nasal epithelial cells through increased TGF-ß1 production |
|
| Tsung-Wei Huang,Ching-Kuo Wei,Huang-Wei Su,Kai-Min Fang | | Journal of Tissue Engineering and Regenerative Medicine. 2016; | | [Pubmed] | [DOI] | | 65 |
Nasal delivery of chitosan-coated poly(lactide-co-glycolide)-encapsulated honeybee (Apis mellifera) venom promotes Th 1-specific systemic and local intestinal immune responses in weaned pigs |
|
| Jin-A Lee,Yun-Mi Kim,Tae-Hoon Kim,Sang-Ho Lee,Cho-A Lee,Cheong-Weon Cho,Jong-woon Jeon,Jin-kyu Park,Sang-Ki Kim,Bock-Gie Jung,Bong-Joo Lee | | Veterinary Immunology and Immunopathology. 2016; | | [Pubmed] | [DOI] | | 66 |
Designing hydrogels for controlled drug delivery |
|
| Jianyu Li,David J. Mooney | | Nature Reviews Materials. 2016; 1(12): 16071 | | [Pubmed] | [DOI] | | 67 |
Formulation and Device Design to Increase Nose to Brain Drug Delivery |
|
| Zachary N. Warnken,Hugh D.C. Smyth,Alan B. Watts,Steve Weitman,John G. Kuhn,Robert O. Williams | | Journal of Drug Delivery Science and Technology. 2016; | | [Pubmed] | [DOI] | | 68 |
Formulation and Development of In Situ Nasal Gelling Systems for Quetiapine Fumarate-Loaded Mucoadhesive Microemulsion |
|
| Nirav Patel,Manoj Baldaniya,Mihir Raval,Navin Sheth | | Journal of Pharmaceutical Innovation. 2015; 10(4): 357 | | [Pubmed] | [DOI] | | 69 |
Effect of surface charge on the brain delivery of nanostructured lipid carriers in situ gels via the nasal route |
|
| Yasmine M. Gabal,Amany O. Kamel,Omaima A. Sammour,Ahmed H. Elshafeey | | International Journal of Pharmaceutics. 2014; 473(1-2): 442 | | [Pubmed] | [DOI] | | 70 |
Mucoadhesive polyethylenimine–dextran sulfate nanoparticles containingPunica granatumpeel extract as a novel sustained-release antimicrobial |
|
| Waree Tiyaboonchai,Ingdao Rodleang,Anan Ounaroon | | Pharmaceutical Development and Technology. 2014; : 1 | | [Pubmed] | [DOI] | |
|
 |
 |
|