Bioadhesive polymers: Novel tool for drug delivery

Figures & data

Figure 1. Mechanism of Mucoadhesion. The mucoadhesion takes place in two stages. (A) Contact stage: Intimate contact between a bioadhesive and a membrane (wetting or swelling phenomenon). (B) Interactive stage: Penetration of the bioadhesive into the tissue or into the surface of the mucous membrane (interpenetration).

Table I. Theories of mucoadhesion.

Theory	Mechanism
Electronic theory	Electron transfer among surfaces resulting in attractive forces (Lee et al. 2000).
Wetting theory	Affinity of the liquid to the substrate inversely dependent on contact angle (Bhalodia et al. 2010).
Adsorption theory	Adhesive interaction among substrate surface depends upon the intermolecular forces such as hydrogen bond, van der Waals forces, etc. (Kumar and Prabhakar 2010).
Diffusion theory	Diffusion of the polymer chains, present on the substrate surfaces, across the adhesive interface thereby forming a networked structure (Jasti et al. 2003).
Mechanical theory	Diffusion of the liquid adhesives into the micro-cracks and irregularities present on the substrate surface thereby forming an interlocked structure which gives rise to adhesion (Smart 2005).
Cohesive theory	Bioadhesion due to the intermolecular forces among like molecules (Andrews et al. 2009).

Table II. Effect of polymer properties on mucoadhesion.

Properties	Effect
Functional group	COOH, OH, NH2, SO4H groups favor mucoadhesion (Capra et al. 2007).
Molecular weight	More is molecular weight (above 100,000) more is the bioadhesion (Sachan and Bhattacharya 2009).
Flexibility	Higher is the flexibility of the polymer more is the diffusion and hence more mucoadhesion (Chowdary and Srinivas 2000).
Chain length	With decrease in chain length interpenetration increases (Boddupalli et al. 2010).
Degree of hydration	Excessive hydration leads to decreased mucoadhesion (Sigurdsson et al. 2006).
Degree of cross-linking	Increased cross-linking decreased mucoadhesion (Imam et al. 2003).
Polymer concentration	For semisolid: increase in concentration decrease mucoadhesion. For solid dosage form: increase in concentration increase mucoadhesion (Ugwoke et al. 2005).
Charge	Nonionic polymers posses less mucoadhesion than ionic, and cationic polymers exhibits more mucoadhesion than anionic (Lehr et al. 1992).

Table III. Bioadhesive property of different polymers.

Polymer	Bioadhesive property
CMC sodium	Excellent
Carbopol	Excellent
Polycarbophil	Excellent
Tragacanth	Excellent
Sodium alginate	Excellent
HPMC	Excellent
Gum karaya	Very good
Gelatin	Very good
Guar gum	Very good
Pectin	Good
Acacia	Good
Chitosan	Good
Hydroxypropyl cellulose	Good

Table IV. Classification of bioadhesive polymers.

Polymers	Examples
Hydrophilic polymers	Methyl Cellulose, hydroxyethyl cellulose, HPMC, Na CMC, carbomers (Ludwig 2005).
Thiolated polymers	Chitosan–iminothiolane, PAA–cysteine, PAA–homocysteine, chitosan–thioglycolic acid, chitosan–thioethylamidine, alginate–cysteine, poly (methacrylic acid)–cysteine and sodium carboxymethylcellulose–cysteine (Schnürch 2005).
Lectin-based polymers	Lentil lectin, peanut agglutinin, ulex europaeus agglutinin (Haltner and Lehr 1997).
Polyox WSR	WSR N-10, WSR N-80, WSR N-205, WSR N-750.
Novel polymers	Tomato lectin, PAA-co-PEG, PSA (Shojaei and Xiaoling 1997).

Figure 2. Different methods for evaluation of mucoadhesive polymers.

Figure 3. Falling liquid film technique for measurement of mucoadhesion.

Table V. Compilation of studies performed for drug delivery using bioadhesive polymers.

Bioadhesive polymer	Drug	Dosage form	Result	Reference
CMC	Pantoprazole	Microspheres	With increase in CMC concentration the mucoadhesive strength and percent drug release increased up to 8 h.	(Arya et al. 2010b).
Gelatin + Na CMC	Aceclofenac	Buccal patch	Sustained release of 88. 4% for 8 h and greater mucoadhesive strength for about 268 min.	(Khairnar, 2009)
CMC	Famotidine	Microspheres	Drug release was increased to 90% in 8 h, and the percent mucoadhesive strength was up to 82% which increased with increase in polymer concentration.	(Arya et al. 2010a)
PEG+ Carbopol+ PVP	Lidocaine	Bioadhesive gel	Addition of carbopol and PVP provides more sustained release.	(Tan et al. 2000)
Carbopol+ HPMC	5-FU	Thermosenstive vaginal gel	Higher anti-cancer activity with controlled release of drug.	(Bilensoy Erem 2007)
Carbopol-934P	Amoxicillin	Microspheres	Gastro retentive with mucoadhesion percent of greater than 80% after 1 h and sustained release for about 12 h.	(Patel and Chavda 2009)
Carbopol-934P	Sumatriptan	Thermosenstive nasal gel	Prolonged nasal residence time and enhanced drug permeation.	(Majithiya et al. 2006)
Polycarbophil	Moxifloxacin	Hydrogel	98% of drug was released 12 h from the hydrogel providing sustained release.	(Dholakia et al. 2012)
HPMC	Losartan potassium	Film	Sustained drug release in the range of 90.10–97.40% for a period of 6 h, slowerpermeation of the drug for 6–7 h.	(Koland et al. 2010)
Tragacanth+ HPMC K4M	Famotidine	Tablets	Increased mucoadhesive property and continuous release of drug at a predetermined rate and for apredetermined time were observed.	(Sankar et al. 2011)
HPMC K4M	Amoxicillin trihydrate	Microspheres	Prolonged gastric residence time and enhanced gastric stability due to mucoadhesive nature of microspheres.	(Singh 2010)
Chitosan	Lidocaine	Films	Sustained release in the range of 90.10–97.40% for a period of 6 h, and ex vivo permeation studies show slow permeation of the drug for 6–7 h.	(Varshosaz and Karimzadeh 2007)
Chitosan	Miconazole	Buccal films	Significant enhancement of miconazole: in vitro release from about 60% (reference) to 94% (optimized film) and superior antifungal activity as compared with miconazole oral gel.	(Bazigha and Abdul 2010)
Chitosan	Carvedilol	Tablet containing drug loaded microspheres	Pharmacokinetic studies showed significantly higher C(max) (71.26 ± 6.45 ng/mL), AUC (0–10) (AUC, area under the curve 390.75 ± 5.23 ng/mL/h) and AUC (0–∞) (664.72 ng/mL/h) than carvedilol oral tablet hence, enhanced bioavailability and sustained release	(Yedurkar et al. 2012)
Sodium Alginate+ Isaphgula	Glicazide	Beads	Drug release was from 73–92% in 10 h and mucoadhesive strength was found to be 66–70% and 38–43% in HCl and PBS, respectively, ex vivo.	(Nayak et al. 2010)
Sodium alginate + chitosan	Gatifloxacin	Nanoparticles	Prolonged ocular residence time for more than 24 h.	(Motwani et al. 2008)

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