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10 The Use of Mucoadhesive Polymers in Buccal Drug Delivery

10 The Use of Mucoadhesive Polymers in Buccal Drug Delivery

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The Use of Mucoadhesive Polymers in Buccal Drug Delivery



New Generation of Mucoadhesive Polymers

Recent report classified bioadhesive polymers as first generation and second

generation polymers [45]. Older generation mucoadhesive polymers also known

as off-the shelf “polymers as they, lack specificity and targeting capability.

These polymers stick to the mucus non-specifically, and undergo short retention

times owing to the turnover rate of the mucus. Non-covalent type of interaction

takes place between mucoadhesive polymers and the mucus or tissue surfaces.

Nevertheless, newer polymers are accomplished in forming covalent bonds with

the mucus and the underlying cell layers., thus show improved chemical interactions. On the other side new generation of mucoadhesives (with the exception

of thiolated polymers) can adhere directly to the cell surface, rather than to

mucus. These mucoadhesives interact with the cell surface by means of specific

receptors or covalent bonding instead of non-specific mechanisms (which are

characteristic of the older polymers). The examples of most developing and

recent bioadhesive polymers are the incorporation of l-cysteine into thiolated

polymers and the target-specific, lectinmediated adhesive polymers. These categories of polymers hold promise for the delivery of a extensive variety of new

drug molecules, specifically macromolecules, and create new possibilities for

more specific drug–receptor interactions and improved targeted drug delivery.


Thiolated Mucoadhesive Polymers

Thiolated mucoadhesive polymers are synthesized by a covalent attachment

between a cysteine (Cys) residue and a polymer of choice, such as polycarbophil [46], poly(acrylic acid) [47], and chitosan [48]. These polymers are known

as a new generation of mucoadhesive polymers. These moderen class of polymers contain a carbodiimide-mediated thiol bond which exhibit much improved

bioadhesive properties.


Target-Specific, Lectin-Mediated Bioadhesive Polymers

Opportunity of synthesizing a bioadhesive polymer to selectively create specific

molecular interactions with a specific target (such as a receptor on the cell membrane of a specific tissue) is a very attractive potential for targeted delivery

(Fig. 6.5). The potential of a specific receptor–bioadhesive polymer interaction

can circumvent the limiting factors of rapid mucus turnover and short residence

time. In contrast with general mucoadhesive polymers (which bind to the mucosal

surface universally) a specific receptor mediated interaction with the mucosal surface could permit for direct binding to the cell surface, rather than only the mucus



Modern Polysaccharides and Its Current Advancements





Adhesive particles

Non Adhesive particles



Fig. 6.5 Plan representation of the interactions of various types of particles with the mucus layer.

(1) After initial administration/arrival to the mucosal site, particles will interact and diffuse via the

mucus in a different way according to their adhesive features. (2) Larger particles are not capable

to diffuse via the mucus layer owing to steric hindrance, but can interact with the luminal layers in

cases where adhesive bonding with mucin chains (in gray) can be recognized. Since for smaller

particles, these can diffuse via the mucus layer depending on adhesive features: diffusion of adhesive NPs is slower as these will be hold on to particularly at the luminal/external layers of mucus

due to interaction with mucin; in the case of non-adhesive NPs, systems with diameters around

200–500 nm can diffuse quickly and reach the epithelial lining, while smaller ones experience

decreased diffusion rates, most probably because of retention in “dead end” pockets of the mucin

mesh. (3) In the lead natural mechanisms of clearance, which are typically felt at the luminal side

of mucus, particles are gradually eliminated from the mucosal site while NPs that have arrived at

the epithelial cell lining can further experience cell uptake or tissue penetration. Legend: A—

mucosal tissue lumen/external environment; B—mucus layer; C—epithelial cell lining

layer. Specific proteins or glycoproteins (which can potentially to bind certain

sugars on the cell membrane) can enhance bioadhesion and potentially improve

drug delivery via specific binding. In addition these proteins can also increase the

residence time of the dosage form and this type of bioadhesion termed as cytoadhesion [49] (Table 6.4).


Mucoadhesive Polssacharides in the Design of NanoDrug Delivery Systems for Non-Parenteral


The occurrence of a mucus layer that present at the surface of various organs has

been exploited to develop mucoadhesive dosage forms. These layers act as

administration site to prolong time, and increase the local and/or systemic bioavailability of the administered drug [58]. The appearance of micro and nanotechnologies simultaneously with the execution of non-invasive and painless

administration routes has transforms the pharmaceutical market and the management of disease. Intending to minimize the chief limitations of the oral route and

6.11 Polysaccharide Based Gene Transfection Agents


Table 6.4 Mucoadhesive polymers in buccal drug delivery

Active ingredient



Chlorhexidine digluconate




Nifedipine or Propranolol



Chitosan and PVP

Polymers used

Chitosan HCl and PAA sodium salt



Gelatin and CP 934P

Gelatin and CMC


Chitosan with or without an anionic crosslinking

polymer (PC, sodium alginate, gellan gum)

Gelatin and CP 934P












to maintain patient acquiescence high, the manufacturing of innovative drug

delivery systems administrable by mucosal routes has come to light and gained

the attention of the scientific community owing to the possibility to considerably

change pharmacokinetics [58]. Moreover, to attain the aim of mucosal drug

administration, the production of biomaterials has been refined to fit specific

applications. Table 6.5 describes the list of potential biomaterials explored as

nano-drug delivery systems for mucosal administration by diverse non-parenteral routes (e.g., oral, inhalatory, etc.).


Polysaccharide Based Gene Transfection Agents

Gene delivery is an excellent technique that involves in vitro or in vivo introduction

of exogenous genes. These genes are introduced into cells for experimental and therapeutic purposes. Optimal gene delivery depends on the development of efficient and

safe delivery vectors. There are two prominent delivery systems, viral and non-viral

gene carriers, are at present deployed for gene therapy. As majority of present gene

therapy clinical trials are based on viral approaches, non-viral gene medicines have

also appeared as potentially safe and successful for the treatment of a wide variety of

genetic and acquired diseases. Non-viral technologies involve plasmid-based expression systems. This contains a gene linked with the synthetic gene delivery vector.

Polysaccharides accumulate a large family of heterogenic sequences of monomers

with various applications and various benefits as gene delivery agents. Current research

progress in polysaccharide based gene delivery is based on the recent developments of

polysaccharide employed for in vitro and in vivo delivery of therapeutically important

nucleotides, e.g. plasmid DNA and small interfering RNA. Polysaccharides can also

offered a stable drug and gene delivery platform [58]. Cationic polysaccharides are

non-toxic, biodegradable and biocompatible materials. They are particularly appropriate for transfection and biological uses as they are water soluble and can be readily

transported to cells in vivo. Therefore these polysaccharides act as effective vehicles



Table 6.5 List of

mucoadhesive polymers in

the design of nano-drug

delivery systems for

administration by nonparenteral routes [58, 59]

Modern Polysaccharides and Its Current Advancements

Mucoadhesive polymers

Natural polymers



Thiolated chitosan

O-Carboxymethyl chitosan

N-trimethyl chitosan

N-carboxymethyl chitosan

Guar gum, xanthan gum and pectin

Galactomannan and glucomannan

Carrageenan-type II

Hyaluronic acid and other glycosaminoglycans


Synthetic polymers

Poly(ethylene glycol) and poly(ethylene oxide) and its


Poly(acrylic acid) and poly(methacrylic acid) derivatives

Poly(vinyl pyrrolidone)

Poly(vinyl amine)

Boronate-containing polymers

Semi-synthetic polymers

Cellulose derivatives

for delivering agents complexed with them [58]. Most of the cationic polysaccharides

employed for gene delivery purposes are either natural or semisynthetic in origin.

Semisynthetic cationic polysaccharides are fabricated by the conjugation of different oligoamines to oxidized polysaccharides e.g. polycations of dextran, pullulan and

arabinogalactan grafted with oligoamines of 2–4 amino groups were also investigated

and were found to be effective in gene delivery [58]. One of the most related features

of this type of carrier is that the polysaccharide hydroxyl groups can be easily modified and possibly the presence of sugar-recognition receptors on the cell surface can

assist internalization [58] (Fig. 6.6).


Polymeric Micro/Nanoparticles: Particle Design

and Potential Vaccine Delivery Applications

Particle based adjuvant endow hopeful signs on transporting antigen to immune

cells and behaving as stimulators to elicit preventive or therapeutic response.

Nevertheless, the wide size distribution of existing polymeric particles has so far

masked the immunostimulative effects of particle adjuvant, and compromised the

development in pharmacological researches [60]. To overcome this obstacle, Yue

et al. has conceded out a series of research activities regarding the particulate










1 2 3

4 5



Fig. 6.6 Mechanism for targeted delivery of nucleotides using cationic polymers and different

cellular barriers for in vitro gene delivery, 1: interaction of DNA nanoparticle with targeted DNA;

2: entry in to the cell; 3: escape from the endosome; 4: dissociation of DNA nanoparticle; 5:

nuclear transport

vaccine, by taking benefit of the successful fabrication of polymeric particles with

uniform size. In this investigation Yue et al. demonstrated the insight and practical

development focused on the effects of physiochemical property and antigen loading mode on the resultant biological/immunological outcome. With the help of a

unique microporous membrane emulsification technique, Yue et al. fabricated particles with uniform and controllable size with good reproducibility. This research

offers roadway for further investigation on biological/immunological response.

Through these particles, the influence of a single property (e.g. size, charge, shape)

can be explained, and the influence of other factors is reduced to guarantee reliable

results. Attractive advantages of successful exploration of particle-bio interaction,

positive charge, smaller size, hydrophobic surface, rod shape, specific chemical

component were implicated in the active immune response. Based on the understanding, particles with high optimized attributes and antigen payload could be

designed for expected adjuvant purpose, resulting in the development of high efficient vaccine candidates [60].


1. Janes KA, Calvo P, Alonso MJ. Polysaccharide colloidal particles as delivery systems for

macromolecules. Adv Drug Deliv Rev. 2001;47:83–97.

2. Shogren RL, Bagley EB. Natural polymers as advanced materials: some research needs and directions. In: Iman SH, Greene RV, Zaidi BR, editors. Biopolymers. Utilizing nature’s advanced materials, ACS symposium series 723. Cary, USA: Oxford University Press; 1999. p. 2–11.

3. Kaplan DL. Introduction to polymers from renewable resources. In: Kaplan DL, editor.

Biopolymers from renewable resources. Berlin, Germany: Springer Verlag; 1998. p. 1–29.

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