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Mucoadhesion & It’s Drug Delivery System: General Overview

Akash Akash, Bhavna Tyagi, Reenu Chauhan, Deepti Aggarwal, Babita Kumar, Ajeet Ajeet*

Sanskar College of Pharmacy & Research, Ghaziabad, India

Abstract: Mucoadhesive drug delivery systems can enhance the bioavailability of drugs by increasing their residence time at the site of absorption. This allows for better absorption and improved therapeutic outcomes. These systems can provide controlled and sustained release of drugs, ensuring a constant and prolonged drug concentration at the site of action. This can reduce the frequency of drug administration and enhance patient compliance. Mucoadhesive drug delivery systems can be designed to target specific sites within the body, such as the gastrointestinal tract or the nasal cavity. This allows for localized drug delivery and minimizes systemic side effects. These advantages make mucoadhesive drug delivery systems a promising approach in the field of drug delivery, offering improved efficacy and patient convenience. This review contains basic general overview of mucoadhesive drug delivery concept.

Keywords: mucoadhesive polymer, mucoadhesion, theory of mucoadhevise

Received December 01, 2023; Revised January 01, 2024; Accepted January 08, 2024

Citation: Akash Akash, Bhavna Tyagi, Reenu Chauhan, Deepti Aggarwal, Babita Kumar, Ajeet Ajeet, Mucoadhesion & It’s Drug Delivery System: General Overview. American Journal of Pharmacological Sciences, 12 (1). 1-7. January 2024. doi:10.12691/ajps-12-1-1

1. Introduction

For patient protection and to maximize the effectiveness in terms of therapeutic action , the existing drug molecules are developed into novel drug delivery system (NDDS) by pharmaceutical researches instead of developing new chemical entities. [1]

Over the past 40 years, researchers have utilized the concept of mucoadhesion to apply it significantly in prolonging the residence time and achieving controlled release effects of bioadhesive dosage forms through various mucosal routes. [2]

Nasal, parenteral, oral, intradermal, rectal, intravaginal , ocular amongst these routes oral route is mostly preferred by the patient for their compliance. [3]

In general, bioadhesive properties are exhibited by various biopolymers and have been utilized for various therapeutic purposes in medicine.Broad classifications into two groups, namely specific and non-specific, can be applied to the bioadhesive polymers. [4]

Excellent opportunities for the delivery of a variety of compounds have been provided by other routes such as nasal, ocular, pulmonary, rectal, and vaginal drug administration. [5]

Currently, the main controlled drug delivery systems available include matrices, pellets, floating systems, liposomes, microemulsions, liquid crystals, solid dispersions, nanosuspensions, transdermal systems, cyclodextrin inclusion complexes, osmotic pumps, and bioadhesive systems. [6]

The mucoadhesive properties of marine carbohydrates with a focus on chitosan, carrageenan, alginate, and their utilization in designing a drug delivery system are to be characterized. [7]

Pharmaceutical developers should design dosage forms for mucoadhesive drug delivery that are small and flexible enough for patient acceptance and do not cause irritation. [7]

Until now, researchers have not developed a standardized method for studying mucoadhesion. [8]

1.1. Overview of Oral Mucosa

The delivery of drugs is provided by both systemic and local pathways. A large surface area of mucous membrane is contained in the oral cavity for the complete absorption of various drugs. The total surface area of the oral cavity, lined by mucous membranes, is approximately 100 cm².Several parts of the oral cavity include:

i). The floor of the mouth (sublingual)

ii). The buccal mucosa (cheeks)

iii). The gums (gingiva)

iv). The palatal mucosa

v). The lining of the lips. [2]

The epithelium of the buccal mucosa is approximately 40-50 cell layers thick, whereas the sublingual epithelium has somewhat fewer layers. [9]

2. Oral Mucosa

Several distinct patterns of maturation in the epithelium of the human oral mucosa are revealed by light microscopy, based on various regions of the oral cavity. The epithelium, basement membrane, and connective tissues are comprised of three distinctive layers of the oral mucosa. [10]

To enhance the bioavailability of therapeutic peptides and proteins in the circulation, one can increase their capability to cross the mucus and/or epithelial cell layers, thereby facilitating their entry into the bloodstream. [11]

2.1.1. Oral Epithelium and Cell Junction

The oral cavity's oral mucosa is functioned by protecting the underlying tissues from mechanical damage, besides serving as a primary barrier site and a portal for the entry of food, microbes, and airborne particles into the gastrointestinal tract. [12]

A subsurface layer of connective tissues (dermis for skin and lamina propria for oral mucosa), containing fibroblasts, macrophages, mast cells, blood vessels, and nerve endings, is embedded in the extracellular matrix (ECM) to provide the epithelium with structural support and nutrients required for continuous renewal, supporting the stratified epithelium. [13]

The delivery of active agents is preferred at the buccal cavity due to its easy access, despite its limited surface area of around 50cm2. An opportunity to deliver pharmacologically active agents systemically, while avoiding hepatic first-pass metabolism, is provided by the site, in addition to the local treatment of oral lesions. [7]

The epithelium, serving as a protective layer for the tissues beneath, is divided into

(a) A non-keratinized surface in the mucosal lining of the soft palate, the netrak surface of the younger, the floor of the mouth, alveolar mucosa, vestibule, lips, and cheeks, and (b) Keratinized epithelium, which is found in the hard palate and non-flexible regions of the oral cavity. The epithelial cells, originating from the basal cells, undergo maturation, shape changes, and size increase as they move towards the surface. [14]

Human and animal mucosa differs in terms of the thickness of the epithelium and the degree of keratinization. The thickness of buccal mucosa in humans, dogs, and rabbits is subject to variation within the range of 500-800 micrometers. [8]

The administration of low-solubility or proteic drugs has been proposed to be facilitated by mucoadhesive nanoparticles, as these carriers may prevent the enzymatic degradation of these substances in the harsh gastrointestinal environment. With this objective, microparticles of Chitosan/gum Arabic PECs were developed for the further oral administration of insulin, thus avoiding the use of parenteral routes for the administration of this protein. [15]

Injury to the oral mucosa causes a break in the barrier function, resulting in loss of tissue fluid, an elevated risk of infection, and potential limitations in oral function. Thus, there is a need for reconstruction to reestablish the anatomical and physiological properties and prevent further complications. [16]

Ionic interactions with anionic substructures of the mucous membrane primarily form the basis for the mucoadhesion of chitosan. [17]

Researchers examined the developed buccal films for mechanical, mucoadhesive, swelling, and release characteristics. [18]

It's main purpose is to serve preclusive. Deeper tissues such as fat, muscles, nerves, and blood vessels are protected from mechanical trauma, such as chewing. The most common disease that affects people is oral mucosal disease. [19]

This review aims to explore the increasing knowledge of the characteristics of oral mucosal remodeling in allergic (food allergy, respiratory allergy) or non-allergic (i.e., celiac disease, a food-induced autoimmune) diseases. [20]

2.1.2. Mucoadhesion

Mucoadhesion is referred to as the adhesion between a polymer and a mucus layer. [21]

The term mucoadhesion is often employed when a mucosal surface is the biological substrate. Likewise, in the gastrointestinal tract, the adhesion of semisolid forms to the mucus is demonstrated by mucoadhesion. [22]

An artificial substance capable of interacting with mucous membranes and being retained on them or holding them together for an extended or prolonged period is defined as mucoadhesive. [23]

The possibility that these polymers can be used to overcome physiological barriers in long-term drug delivery has been brought to the attention of many investigators by the concept of mucoadhesives. [24]

2.1.3. Factors Affecting Mucoadhesion in Oral Cavity

Several factors, including swelling, molecular weight, and flexibility of the polymer chain, along with the formation of chemical bonding, determine the ability of a polymer to attach to the mucus layer. [21]

1). Molecular weight- When the molecular weight is more than 100,000 the bioadhesive strength of polymer increases. [25]

2). Flexibility of the polymer chain- The diffusion of the polymer chain in the interfacial region starts the bioadhesion. So, a substantial degree of flexibility is required to obtain desired quagmire with the mucous by the polymer chain. [5]

3). Cross-linking density- Three important and interrelated structural parameters of a polymer network are the average pore size, the number average molecular weight of the cross-linked polymers, and the density of the cross-linking.Therefore, it appears reasonable that, with an increase in the density of cross-linking, the diffusion of water into the polymer network is experienced at a lower rate, consequently leading to a lessened swelling of the polymer and a decreased rate of interpenetration between the polymer and mucin.This general property of polymers, in which the degree of swelling at equilibrium has an inverse relationship with the degree of cross-linking of a polymer, has been reported by Flory. [5]

4). Concentration of active polymer- An optimum concentration of a bioadhesive polymer is required to achieve maximum bioadhesion.In highly concentrated systems, beyond the optimum level, the adhesive strength is significantly decreased because the coiled molecules are separated from the medium, limiting the chain available for interaction.The higher concentration of polymer results in larger penetrating chain and better adhesion. [1]

5). Hydration (Swelling Property)-The swelling property of the mucoadhesive microspheres was ranged from 53.27% to 70% for Chitosan microspheres and from 43.82% to 58% for Eudragit L 100 microspheres.Rapid swelling in Stimulated Nasal Fluid (SNF) was observed in all obtained microspheres. [26]

6). Hydrogen Bonding Capacity-The importance of hydrogen bonding in mucoadhesion of a polymer is underscored.The formation of hydrogen bonds is desired in polymers, and the improvement of this hydrogen bonding potential is deemed important, with flexibility being considered.Good hydrogen bonding capacity is exhibited by polymers such as polyvinyl alcohol, hydroxylated methacrylate, and poly methacrylic acid, as well as all their copolymers. [7]

2.1.4. Characterstics

Following characteristics are required for an ideal mucoadhesive polymer

1). It should be non-absorbable from gastrointestinal tract. [27]

2). It should be non-toxic. [28]

3). It should not cause irritation to the mucous membrane. [1]

4). It should specially form a strong non-covalent bond with the surfaces of mucin-epithelial cells. [28]

5). It should allow daily illatuion to the drug and do not provide obstacles for its release. [29]

6). The polymer should not be degrade during storage or during the shelf life of dosage form. [27]

7). The cost of the polymer should be reliable. [24]

8). It has high chain flexibility. [29]

2.1.5. Mechanism of Mucoadhesion

The mucoadhesion process is initiated through two stages, involving the connection between the mucoadhesive material (formulation) and the mucous membrane. [30]

The use of MRI is employed to detect the time and location of disintegration of the fast-releasing delivery system. [31]

Mucoadhesion involves attaching the drug, along with a suitable carrier, to the mucous membrane.

The complex phenomenon of mucoadhesion involves wetting, adsorption, and interpretation of polymer chains. [32]

Different mechanisms of adhesion to mucosa could exist and depend on the nature of a dosage form.

Contact stage-It explains the connection between the mucous membrane and the mucoadhesive polymer, with the dispersal and swelling of the formulation. [28]

Consolidation stage The presence of moisture activates the mucoadhesive material in the consolidation step.The system is plasticized by moisture, enabling the mucoadhesive molecules to break free and be linked up by weak Van der Waals and hydrogen bonds. Essentially, two theories are used to explain the consolidation step: the diffusion theory and the dehydration theory. [33]

Figure 1. Mechanism of mucoadhesion

2.1.6. Mucoadhesion Theories

Mucoadhesion is a complicated process various theroies are there to explain the mechanism:

1. The Diffusion theory

2. The Wetting theory

3. The Cohesive theory

4. The Mechanical theory

5. The electronic theory

6. The Absorption theory

7. The Fracture theory

Figure 2. Mucoadhesive behavior : Different theories A: Electronic theory, B: Adsorption theory, C: Wetting theory, D: Diffusion theory, E: Fracture theory

1). The diffusion theory: A networked structure across the adhesive interface is formed by the presence of polymeric chain on the substrate surface [34]. Upon initial contact with these two polymers, i.e., glycoproteins of the mucus and mucoadhesive polymer chain, an entangled network is created between the two polymers through the diffusion of the mucoadhesive polymer chain into the mucus network. [36]

2). The wetting theory: The spreading of the material, mostly mucoadhesive liquids or low viscous formulations, is described by the Weeting theory on biological tissues.An extension of Young's basic equation can calculate the degree of spreading. [8] Bioadhesion is expressed as an incrustation process wherein mucosal surface irregularities are penetrated by the bioadhesive polymers. [37]

3). The cohesive theory: The occurrence of bioadhesion is basically due to the intermolecular interactions among like molecules. [4]

4). The mechanical theory: The diffusion of the liquid adhesives into the micro-cracks and irregularities present on the substrate surface, thereby forming an interlocked structure that gives rise to adhesion, is explained by the mechanical theory. [4] The presence of irregularities in the mucosal surface creates a liquid adhesiveness, increasing the area of contact between the polymer and the mucosa. [15]

5). The electronic theory: The transfer of electrons among the surfaces is proposed by the electronic theory, resulting in the formation of an electrical double layer, thereby giving rise to attractive forces. [1] The electronic hypothesis is concerned with the principle that divergent electrical charges are acquired jointly by mucoadhesive and biological materials. Thus, when both resources come into contact, electrons are exchanged to construct a two-fold electronic layer at the boundary, where the mucoadhesive potency is determined by the striking forces within these electronic layers. [38]

6). The adsorption theory: The mucoadhesive device is adhered to the mucus by secondary chemical interactions, such as Van der Waals and hydrogen bonds, electrostatic attractions, or hydrophobic interactions, according to the Adsorption Theory. For example, in polymers containing carboxyl groups, the prevalent interfacial forces are constituted by hydrogen bonds. Researchers have considered such forces to be the most important in the adhesive interaction phenomenon number of interactions can achieve intense global adhesion. [39]

7). The fracture theory: This theory explains the forces required to separate the two surfaces after adhesion has taken place. [40]

2.1.7. Classes of Mucoadhesive Polymers

The achievement of mucoadhesivity in dosage forms is typically accomplished by the incorporation of hydrophilic polymers in formulations, which are often known for their ability to exhibit good stability in adhering to mucosal membranes. Polymers that possess charged groups or non-ionic functional groups capable of forming hydrogen bonds with mucosal surfaces typically exhibit excellent mucoadhesive performance.

The polymeric structural characteristics necessary for mucoadhesion can be summarized as follows:

i). Include strong hydrogen groups like carboxyl, hydroxyl, and sulfate groups.

ii). Incorporate strong anionic or cationic charges.

iii). Feature high molecular weight.

iv). Demonstrate chain flexibility.

v). Exhibit surface energy properties that favor spreading onto mucus.Different classes of mucoadhesive polymers will be considered below in relation to their chemical structure and functionality. [34]

2.1.8. Uses of Polymers in Newer MDDS

The usage of mucoadhesive polymers for non-parenteral delivery systems has been described in a recent review by Sosnik et al.According to the authors, nanoparticulate mucoadhesive delivery systems can be formulated using all three types of polymers, including natural, synthetic, and semi-synthetic ones.In another interesting work, the formulation of HPMC-coated buccal apogee loaded with carvedilol nanoemulsion has been explained by Abd-Ekvarry et al. [25]

3. Recent Advancement of Mucoadhesion Test

Mucoadhesion studies have recently been reported using BIACORE integrated chip IC systems.In this process, you immobilize the polymer (powder) onto the surface of the IC and then pass the mucin solution over it.The interaction of the mucin with the polymer surface arises as a result of this. [40] The measurement of the polymer-mucin interaction is performed by an optical phenomenon known as Surface Plasmon Resonance (SPR), which quantifies the change in refractive index when mucin binds to the polymer surface. [4]

Figure 3. Classes of mucoadhesives

4. Evaluation of Mucoadhesive Polymers

Ex-vivo permeation study: The ex-vivo drug permeation study of microspheres was conducted using a glass-fabricated Franz diffusion cell, with goat nasal mucosa employed as the diffusion barrier.Before carefully dispersing the weighed quantity of 10mg microspheres into the donor compartment, the mucosa was equilibrated.Phosphate buffer solution (pH=6.6) within the pH range of the nasal cavity was used to fill the receptor compartment.The donor compartment was positioned in a manner where it came into slight contact with the diffusion medium in the receptor compartment.A temperature of 37±1 degree Celsius was upheld using a circulating water bath.Samples were periodically withdrawn from the receptor compartment, replaced with an equivalent amount of fresh pre-warmed buffer solution, and subjected to assay using a UV Spectrophotometer at 229nm. [26]

Researchers have developed quite a lot of methods for evaluating the mucoadhesive characteristics of pharmaceutical composition and excipients to date, but certain restrictions have prevented any of these methods from becoming pharmacopeia. [41]

Few researchers demonstrates the suitability of ATR-FTIR spectroscopy for screening the mucoadhesive properties of polymers for a mucoadhesive drug delivery system. [42]

Fluorescent probe method: In this method, the membrane lipid bilayer was labeled with pyrene, and membrane proteins were labeled with fluorescein isothiocyanate.The mucoadhesive agents were mixed with the cells, and changes in fluorescence spectra were monitored.A direct indication of polymer binding and its influence on polymer adhesion was provided by this. [28]

Rheological Study: An acceptable in-vitro model can be offered by the rheological information of polymer-mucus mixtures, which can be correlated with the in-vivo performance of mucoadhesive polymers.The best method for the determination of mucoadhesive potential of a polymer involves comparing binary mucus/polymer blends to the equally concentrated monocomponent mucus/polymer system.Techniques such as chain interlocking and chemical interactions induced by the bioadhesive polymer can alter the rheological behavior of two macromolecular species, including mucin chains. [2]

The mucoadhesion process is a phenomenon in which different interaction types are combined, and rheological methods are used to evaluate the interactions between mucin and polymeric systems. [43]

Flow Rheometry Studies: Viscosity and flow properties were measured at 25 and 37°C.The ease of the administration of the product into the buccal cavity (generally at room temperature) by spraying and the time-dependent clearance of the formulation after administration (at physiological temperature) may be determined by these properties. [44]

Measurement of adhesive strength by falling sphere method: The falling sphere method was employed for the characterization of mucoadhesive strength.Mucus was extracted from the intestine by forceps and was subsequently filled into a clean burette.They took mustard grains and coated them with the test material (MMZ) and the standard (Guar Gum and HPMC E5LV), then slowly placed them at the top of the mucus layer.They noted the time taken to cover 50 divisions in the burette. [45]

Thumb Test: Researchers measure adhesiveness by assessing how difficult it is to pull the thumb from the adhesive, taking into account pressure and contact time.Although the thumb test may not provide conclusive results, useful information on the peel strength of the polymer is yielded by it. [28]

GI Transit study using radio-opaque markers: A simple procedure utilizes radio-opaque markers, such as barium sulfate encapsulated in bioadhesive, to determine the effects of bioadhesive polymers on GI transit time.Using an automated faeces collection machine and X-ray inspection, one can employ a non-invasive method to monitor total GI residence time without affecting normal GI motility. [46]

5. Mucoadhesive Drug Delivery System

The different mucoadhesive dosage forms include tablets, films, gels, ointments, and patches. Mucoadhesive tablets are small, flat, and oval, with the potential for controlled release drug delivery. They adhere to the mucosa, are retained in position until dissolution is complete, and offer efficient absorption and enhanced bioavailability of drugs. Mucoadhesive films are preferred for their flexibility and comfort, and they help protect wound surfaces and reduce pain. Mucoadhesive gels provide extended retention time in the oral cavity and are used for local delivery of medicinal agents. Ointments are developed from highly viscous gels and can be maintained on tissue for up to 8 hours. Additionally, patches and inserts are used for ocular and vaginal delivery, and they help minimize the rapid removal of active medicaments. These various mucoadhesive dosage forms offer advantages such as prolonged residence time at the site of absorption and improved drug plasma concentrations and therapeutic activity.

The common sites for mucoadhesive drug delivery systems include the oral cavity, eye conjunctiva, vagina, nasal cavity, and gastrointestinal tract (GIT). Each site offers specific advantages and disadvantages, such as the buccal and sublingual sites providing fast onset and bypassing first-pass metabolism, but suffering from taste and food intake inconvenience. The GIT offers improved absorption but has drawbacks of acid instability and first-pass effects. Rectal and vaginal sites are suitable for local drug action but suffer from administration inconvenience. Nasal and ophthalmic routes face challenges due to mucociliary drainage that can clear the dosage form from the site. Each site presents unique opportunities and challenges for the delivery of mucoadhesive drug delivery systems.

The factors affecting mucoadhesion include molecular weight, flexibility, cross-linking density, hydrogen bonding capacity, hydration, charge, and concentration. The mucoadhesive strength of a polymer increases with molecular weights above 100,000, and a direct correlation between the mucoadhesive strength of polyoxyethylene polymers and their molecular weights lies in the range of 200,000–7,000,000. Flexibility of polymer chains is important for achieving the desired entanglement with the mucus, and increased chain interpenetration is attributed to the increased structural flexibility of the polymer. Cross-linking density, hydrogen bonding capacity, and hydration are also crucial factors influencing mucoadhesion. Additionally, the charge of bioadhesive polymers, such as anionic or cationic properties, and the concentration of the polymer play significant roles in the development of a strong adhesive bond with the mucus. These factors collectively contribute to the effectiveness of mucoadhesive drug delivery systems.

Mucoadhesive drug delivery systems offer several advantages over other oral controlled release systems. These systems prolong the residence time of the drug in the gastrointestinal tract, allowing for targeting and localization of the dosage form at a specific site. They also provide intimate contact between the dosage form and the absorptive mucosa, leading to improved drug plasma concentrations and therapeutic activity. Additionally, mucoadhesive systems can be tailored to adhere to various mucosal tissues, offering the potential for localized as well as systemic controlled release of drugs. Other advantages include the potential for sustained release, reduced frequency of drug administration, improved patient compliance, and enhanced bioavailability of drugs due to high drug flux at the absorbing tissue. Overall, mucoadhesive drug delivery systems have the potential to improve therapeutic performance and offer targeted drug delivery at specific sites within the body. [51]

Acknowledgements

The authors are very much thankful to Dr. Shabnam Ain (H.O.D., SCPR) & Dr. Q. Ain (Head R&D, SCPR) for their support towards completion of this manuscript.

References

[1]   | Kumar yadav, V., Gupta, A.B., Kumar, R., Yadav, J.S., Hasha, and Kumar, B, “Mucoadhesive Polymers: Means of Improving the Mucoadhesive Properties of Drug Delivery System,” Journal of Chemical and Pharmaceutical Research, 2(5). 418-432. 2010.
[2]   | Singh, R., Sharma, D. and Garg, R, “Review on Mucoadhesive Drug Delivery System with Special Emphasis on Buccal Route: An Important Tool in Designing of Novel Controlled Drug Delivery System for the Effective Delivery of Pharmaceuticals”, Kaufmann Publishers, Boston, 30-35. 2017.
[3]   | Twana Mohammed M. Ways., Wing Man Lau, and Vitaliy V. K, “Chitosan and Its Derivatives for Application in Mucoadhesive Drug Delivery Systems,” Polymers, 10, 267-304. 2018.
[4]   | Roy, S., Pal, K., Anis, A., Pramanik, K. and Prabhakar, B, “Polymers in Mucoadhesive Drug-Delivery Systems: A Brief Note,” Designed Monomers and Polymers, 483–495. 2009.
[5]   | Nazila Salamat-Miller., Montakarn Chittchang, and Thomas P. Johnston, “The use of mucoadhesive polymers in buccal drug delivery,” Advanced Drug Delivery Review, 57(11). 1666-1691. 2005.
[6]   | Carvalho, F.C., Bruschi M.L, Raul Cesar Evangelista. and Maria Palmira Daflon Gremião, “Mucoadhesive drug delivery systems,” Brazilian Journal of Pharmaceutical Sciences, 46. 2010.
[7]   | Bindu M. Boddupalli, Zulkar N.K., Mohammed, Ravinder Nath A., David Banji, “Mucoadhesive drug delivery system: An overview,” Journal of Advanced Pharmaceutical Technology & Research, 1. 2010.
[8]   | Woertz, C., Preis, M., Breitkreutz, J., Kleinebudde, P, “Assessment of test methods evaluating mucoadhesive polymers and dosage forms: An overview,” European Journal of Pharmaceutics and Biopharmaceutics, 2013.
[9]   | Priya Mahajan, Amanpreet Kaur, Geeta Aggarwal, S.L. Harikumar, “Mucoadhesive Drug Delivery System: A Review,” International Journal of Drug Development & Research, 5(1). 11-20. 2013.
[10]   | Chatterjee, B., Amalina, N., Sengupta, P, and Uttam Kumar Mandal, “Mucoadhesive Polymers and Their Mode of Action: A Recent Update,” Journal of Applied Pharmaceutical Science, 7(05). 195-203. 2017.
[11]   | Nirnoy Dan., Kamalika Samanta, and Hassan Almoazen, “An Update on Pharmaceutical Strategies for Oral Delivery of Therapeutic Peptides and Proteins in Adults and Pediatrics,” Children, 7. 307-335. 2020.
[12]   | Sevda Senel, “An Overview of Physical, Microbiological and Immune Barriers of Oral Mucosa,” International Journal of Molecular Sciences, 22. 7821-7836. 2021.
[13]   | Maaike Waasdorp., Bastiaan P. Krom., Floris J. Bikker., Paul P. M. van Zuijlen., Frank B. Niessen. and Susan Gibbs, “The Bigger Picture: Why Oral Mucosa Heals Better Than Skin,” Biomolecules, 11. 1165-1187. 2021.
[14]   | Golshani, S., Alireza Vatanara., Mohsen Amin, “Recent Advances in Oral Mucoadhesive Drug Delivery,” J Pharm PharmSci, 25. 201-217. 2022.
[15]   | RaúlCazorla-Luna., Araceli Martín-Illana., Fernando Notario-Pérez., Roberto Ruiz-Caro, and María-Dolores Veiga, “Naturally Occurring Polyelectrolytes and Their Use for the Development of Complex-Based Mucoadhesive Drug Delivery Systems: An Overview,” Polymers, 13. 2241-2268. 2021.
[16]   | Daniela S. Masson-Meyersa., Luiz E. Bertassonib. And LobatTayebi, “Oral mucosa equivalents, prevascularization approaches and potential applications,” Connect Tissue Res., 63(5). 514–529. 2022.
[17]   | Vjera Grabovac, Davide Guggi, Andreas Bernkop-Schnu¨rch, “Comparison of the mucoadhesive properties of various polymers,” Advanced Drug Delivery Reviews, 57. 1713-1723. Jul.2005.
[18]   | Anroop B. Nair., Jigar Shah., Shery Jacob., Bandar E. Al-Dhubiab., Vimal Patel., Nagaraja Sreeharsha. Pottathil Shinu, “Development of Mucoadhesive Buccal Film for Rizatriptan:In Vitro and In Vivo Evaluation,” Pharmaceutics, 13. 728-744. 2021.
[19]   | Nikita Harekrishna G. Prerana Shantinath H., “Development and Evaluation of In Situ Gel Formation for Treatment of Mouth Ulcer,” Turk J Pharm Sci, 20(3). 185-197. 2023.
[20]   | Cristina Gomez-Casado., Javier Sanchez-Solares., Elena Izquierdo., Araceli Díaz-Perales., Domingo Barber. And María M. Escribese, “Oral Mucosa as a Potential Site for Diagnosis and Treatment of Allergic and Autoimmune Diseases,” Foods, 10. 970-992. 2021.
[21]   | Cho-A Lee., Bo-Sik Kim., Cheong-Weon Cho, “Quantitative evaluation of mucoadhesive polymers to compare the mucoadhesion,” Journal of Pharmaceutical Investigation, 2016.
[22]   | Hailemichael Embafrash Berhe., Desta Tesfay Mezgebo., Solomon Abrha., Tsadkan Gebremeskel Haile, and Fantahun Molla, “Extraction, Characterization, and Evaluation of Lepidiumsativum Linn. Mucilage as a Mucoadhesive Polymer,” Advances in Pharmacological and Pharmaceutical Sciences, 2023.
[23]   | Singh, R., Sharma, D., and Garg. R, “Review on Mucoadhesive Drug Delivery System with Special Emphasis on Buccal Route: An Important Tool in Designing of Novel Controlled Drug Delivery System for the Effective Delivery of Pharmaceuticals,” Journal of Developing Drugs, 6(1). 2017.
[24]   | Hung Thanh Lam., OˇzbejZupanˇciˇc., Flavia Laffleur. and Andreas Bernkop-Schnürch, “Mucoadhesive properties of polyacrylates: Structure–Function relationship,” International Journal of Adhesion and Adhesives, 2021.
[25]   | Bappaditya Chatterjee, Nursazreen Amalina, Pinaki Sengupta, Uttam Kumar Mandal, “Mucoadhesive Polymers and Their Mode of Action: A Recent Update,” Journal of Applied Pharmaceutical Science, 7(05), 195-203. 2017.
[26]   | Khan, S., Purushottam Shridhar Gangane, Debarshi Kar Mahapatra, Nilesh Manoharrao Mahajan, “Natural and Synthetic Polymers Assisted Development of Lurasidone Hydrochloride Intranasal Mucoadhesive Microspheres,” Indian Journal of Pharmaceutical Education and Research, 54. 2020.
[27]   | Mythri .G, K. Kavitha, M. Rupesh Kumar, Sd. Jagadeesh Singh, “Novel Mucoadhesive Polymers –A Review,” Journal of Applied Pharmaceutical Science, 01(08). 37-42. 2011.
[28]   | Saraswathi, B., Balaji, A., and M.S. Umashankar, “Polymers in mucoadhesive drug delivery system-latest updates,” International Journal of Pharmacy and Pharmaceutical Sciences, 5(3). 423-430. 2013.
[29]   | Madan Jyotsana., BanodeSagar, and Dangi Mahesh, “Mucosal drug delivery system,” International Journal of Research in Ayurveda & Pharmacy, 1(1). 63-70. 2010.
[30]   | Parthasarathi Subramanian, “Mucoadhesive Delivery System: A Smart Way to Improve Bioavailability of Nutraceuticals,” Foods, 10. 1362-1384. 2021.

[31]  
Christian Kremsera., Karin Albrechtb., Melanie Greindlb., Christian Wolf a., Paul Debbagec, and Andreas Bernkop-Schnürchb, “In vivo determination of the time and location of mucoadhesive drug delivery systems disintegration in the gastrointestinal tract,” Magnetic Resonance Imaging, 26. 638–643. 2008.

[32]   | Shaffi Khurana and N.V. Satheesh Madhav, “Mucoadhesive drug delivery: mechanism and methods of evaluation,” International Journal of Pharma and Bio Sciences, 2(1). 458-467. 2011.
[33]   | Flávia Chiva Carvalho, Marcos Luciano Bruschi, Raul Cesar Evangelista, and Maria Palmira Daflon Gremião1, “Mucoadhesive delivery systems,” Brazilian Journal of Pharmaceutical Sciences, 46. 2010.
[34]   | Vitaliy V. Khutoryanskiy, “Advances in Mucoadhesion and Mucoadhesive Polymers,” Macromol. Biosci, 11. 748–764. 2011.
[35]   | Hamde Nazar., Marta Roldo., Dimitrios G Fatouros., Susanna M van der Merwe, and John Tsibouklis, “Hydrogels in mucosal delivery,” Therapeutic Delivery, 3(4). 535-555. 2012.
[36]   | Dattatraya Manohar Shinkar., Avinash Sridhar Dhake, and Chitral Mallikarjuna Setty, “Drug Delivery from the Oral Cavity: A Focus on Mucoadhesive Buccal Drug Delivery Systems,” PDA Journal of Pharmaceutical Science and Technology, 66. 466-500. 2012.

[37]  
Graciela Lizeth., Pérez-González., Luis Jesús Villarreal-Gómez., Aracely Serrano-Medina., Erick José Torres-Martínez, and José Manuel Cornejo-Bravo, “Mucoadhesive electrospun nanofibers for drug delivery systems: applications of polymers and the parameters’ roles,” International Journal of Nanomedicine , 14. 5271–5285. 2019.

[38]   | Someshwar Komati1., Suryakanta Swain., Muddana Eswara Bhanoji Rao., Bikash Ranjan Jena, and Vishali Dasi, “Mucoadhesive Multiparticulate Drug Delivery Systems: An Extensive Review of Patents,” Advanced Pharmaceutical Bulletin, 9(4). 521-538. 2019.
[39]   | Dhutwalia, P., Kanwar, K., Anju, Amrit and Ankush, “A review on mucoadhesive drug delivery systems: A novel approach,” International Journal of Pharmaceutical, Chemical and Biological Sciences, 4(2). 277-290. 2014.
[40]   | Pranshu Tangri, and N.V. Satheesh Madhav, “Oral mucoadhesive drug delivery systems: a review, International Journal of Biopharmaceutics, 2(1). 36-46. 2011.
[41]   | Elena Bakhrushina., Maria Anurova., Natalia Demina., Alena Kashperko., Olga Rastopchina., Alexander Bardakov., and Ivan Krasnyuk, “Comparative Study of the Mucoadhesive Properties of Polymers for Pharmaceutical Use” Open Access Macedonian Journal of Medical Sciences, 8(A). 639-645. 2020.

[42]  
Prangtip Uthaiwat, Aroonsri Priprem, Ploenthip Puthongking., Jureerut Daduang, Chatchanok Nukulkit, Sirinart Chio-Srichan., Patcharee Boonsiri, and Suthasinee Thapphasaraphong, “Characteristic Evaluation of Gel Formulation Containing Niosomes of Melatonin or Its Derivative and Mucoadhesive Properties Using ATR-FTIR Spectroscopy,” Polymers, 13. 1142-1158. 2021.

[43]   | Jéssica Bassi da Silva., Sabrina Barbosa de Souza Ferreira, Adriano Valim Reis, Michael Thomas Cook, Marcos Luciano Bruschi, “Assessing Mucoadhesion in Polymer Gels: The Effect of Method Type and Instrument Variables,” Polymers, 10. 254-273. 2018.

[44]  
Raul Diaz-Salmeron, Balthazar Toussaint, Nicolas Huang, Etienne Bourgeois Ducournau, Gabriel Alviset, Sophie GoulayDufaÿ, Hervé Hillaireau, Amélie Dufaÿ Wojcicki, Vincent Boudy, “Mucoadhesive Poloxamer-Based Hydrogels for the Release of HP-CD-Complexed Dexamethasone in the Treatment of Buccal Diseases,” Pharmaceutics, 13. 117-143. 2021.

[45]   | Singh Sudarshan, Bothara Sunil B, “In vivo mucoadhesive strength appraisal of gum Manilkarazapota,” Brazilian Journal of Pharmaceutical Sciences, 51. 2015.
[46]   | B. Saraswathi, Anna Balaji, M.S. Umashankar, “Polymers in mucoadhesive drug delivery system-latest updates,” International Journal of Pharmacy and Pharmaceutical Sciences, 5(3).423-430. Jun.2013.
[47]   | Toril Andersen., Stefan Bleher., Gøril EideFlaten., Ingunn Tho., Sofia Mattsson, and Nataša Škalko-Basnet, “Chitosan in Mucoadhesive Drug Delivery: Focus on Local Vaginal Therapy,” Mar. Drugs, 13. 222-236. 2015.
[48]   | Ruairí P. Brannigan and Vitaliy V. Khutoryanskiy, “Progress and Current Trends in the Synthesis of Novel Polymers with Enhanced Mucoadhesive Properties,” Macromol. Biosci, 2019.
[49]   | Nathaly Vasquez-Martínez., Daniel Guillen., Silvia Andrea Moreno-Mendieta., Sergio Sanchez, and Romina Rodríguez-Sanoja, “The Role of Mucoadhesion and Mucopenetration in the Immune Response Induced by Polymer-Based Mucosal Adjuvants,” Polymers, 15. 1615-1641. 2023.
[50]   | Irina M. Yermak., Viktoriya N. Davydova, and Aleksandra V. Volod’ko, “Mucoadhesive Marine Polysaccharides,” Mar. Drugs, 20. 522-547. 2022.
[51]   | Bindu M. Boddupalli, Zulkar N. K. Mohammed, Ravinder Nath A., David Banji. “Mucoadhesive drug delivery system: An overview”. Journal of Advanced Pharmaceutical Technology & Research, 1(4). 2010.