Delivery of bioactive peptides and proteins across oral (Buccal) mucosa

The identification of an increasing array of highly potent, endogenous peptide and protein factors termed cytokines, that can be efficiently synthesized using recombinant DNA technology, offers exciting new approaches for drug therapy. However, the physico-chemical and biological properties of these agents impose limitations in formulation and development of optimum drug delivery systems as well as on the routes of delivery. Oral mucosa, including the lining of the cheek (buccal mucosa), floor of mouth and underside of tongue (sublingual mucosa) and gingival mucosa, has received much attention in the last decade because it offers excellent accessibility, is not easily traumatized and avoids degradation of proteins and peptides that occurs as a result of oral administration, gastrointestinal absorption and first-pass hepatic metabolism. Peptide absorption occurs across oral mucosa by passive diffusion and it is unlikely that there is a carrier-mediated transport mechanism. The principal pathway is probably via the intercellular route where the major permeability barrier is represented by organized array of neutral lipids in the superficial layers of the epithelium. The relative role of aqueous as opposed to the lipid pathway in drug transport is still under investigation; penetration is not necessarily enhanced by simply increasing lipophilicity, for other effects, such as charge and molecular size, also play an important role in absorption of peptide and protein drugs. Depending on the pharmacodynamics of the peptides, various oral mucosal delivery systems can be designed. Delivery of peptide/protein drugs by conventional means such as solutions has some limitations. The possibility of excluding a major part of drug from absorption by involuntary swallowing and the continuous dilution due to salivary flow limits a controlled release. However these limitations can be overcome by adhesive dosage forms such as gels, films, tablets, and patches. They can localize the formulation and improve the contact with the mucosal surface to improve absorption of peptides and proteins. Addition of absorption promoters/permeabilizers in bioadhesive dosage forms will be essential for a successful peptide/protein delivery system

Development of a buccal bioadhesive nicotine tablet formulation for smoking cessation

Bioadhesive buccal tablet formulations for delivery of nicotine into the oral cavity were developed. Carbomer (Carbopol®974P NF) (CP) and alginic acid sodium salt (NaAlg) were used as bioadhesive polymers in combination with hydroxypropyl methylcellulose (HPMC) at different ratios. Magnesium carbonate was incorporated into the formulations as a pH increasing agent. In vitro release and bioadhesion studies were performed on the developed tablets. In the formulations containing CP:HPMC, the NHT released increased with the increasing HPMC concentration whereas a decrease was observed with increasing HPMC concentration in formulations containing NaAlg:HPMC. The bioadhesive properties of the tablets containing NaAlg:HPMC was not affected by the concentration of the NaAlg (P>0.05) but increased significantly with the increasing CP concentration (P<0.05). A decrease in pH of the dissolution medium to acidic values was avoided by incorporation of magnesium hydroxide into the formulations. The developed formulations released NHT for 8 h period, and remained intact except for the formulation containing CP:HPMC at 20:80 ratio

Effect of chitosan on a periodontal pathogen porhyromonas gingivalis

Local delivery systems of antimicrobial agents for treatment of the periodontal diseases received considerable attention during the past decade due to the disadvantages of the systemic administration. An ideal formulation should exhibit ease of delivery, a good retention at the application site, and a controlled release of the drug. The application of bioadhesive gels provides a long stay in the oral cavity, adequate drug penetration, high efficacy and acceptability. In dentistry and oral medicine, various applications of chitosan, which is a bioadhesive polymer have been proposed due to its favorable properties such as biocompatibility and biodegradability. The aim of this study was to determine the antimicrobial activity of chitosan formulations either in gel or film form against a periodontal pathogen, Porphyromonas gingivalis. The viscosity, bioadhesive properties and antimicrobial activity of chitosans at different molecular weight and deacetylation degree were evaluated in the absence or presence of chlorhexidine gluconate (Chx), incorporated into the formulations at 0.1 and 0.2% concentrations. The flow property of the gels were found to be suitable for topical application on the oral mucosa and to syringe into the periodontal pocket. Bioadhesion of the gels and films examined ex-vivo using fresh porcine buccal mucosa showed that both the film and gel formulations exert bioadhesive properties and was not affected by incorporation of Chx. Chitosan is shown to have an antimicrobial activity against P. gingivalis and this was higher with high molecular weight chitosan. The combination of chitosan with Chx showed a higher activity when compared to that of Chx alone, which would provide Chx application at lower concentrations thus avoiding its unwanted side effects. Chitosan films and gels seem to be promising delivery systems for local therapy of periodontal diseases with its bioadhesive property and antimicrobial activity

Characterization Of Protein And Peptide Binding To Nanogels Formed By Differently Charged Chitosan Derivatives

Chitosan (Chi) is a natural biodegradable cationic polymer with remarkable potency as a vehicle for drug or vaccine delivery. Chi possesses multiple groups, which can be used both for Chi derivatization and for particle formation. The aim of this work was to produce stable nanosized range Chi gels (nanogels, NGs) with different charge and to study the driving forces of complex formation between Chi NGs and proteins or peptides. Positively charged NGs of 150 nm in diameter were prepared from hexanoyl chitosan (HC) by the ionotropic gelation method while negatively charged NGs of 190 nm were obtained from succinoyl Chi (SC) by a Ca2+ coacervation approach. NGs were loaded with a panel of proteins or peptides with different weights and charges. We show that NGs preferentially formed complexes with oppositely charged molecules, especially peptides, as was demonstrated by gel-electrophoresis, confocal microscopy and HPLC. Complex formation was accompanied by a change in zeta-potential and decrease in size. We concluded that complex formation between Chi NGs and peptide/proteins is mediated mostly by electrostatic interactions.PubMedWoSScopu

Two Percent Chitosan Mouthwash: A Microbiological And Clinical Comparative Study

Background/purpose: The aim of this study was to evaluate the microbiological and clinical effects of a chitosan (CH) mouth rinse on plaque inhibition. Materials and methods: Thirty-six healthy participants were recruited. The following clinical data were recorded: a plaque index (PI), gingival index (GI), Quickley-Hein plaque index (QPI), and probing depth (PD). Volunteers were given oral hygiene (OH) instruction and trained on scaling and professional tooth cleaning (PTC). After the final PTC, volunteers were randomly allocated into three groups. Group A rinsed with 2% CH, group B rinsed with 0.2% chlorhexidine digluconate (CHX), and group C rinsed with 2% CH 0.2% CHX. Plaque samples were collected and assayed for Streptococcus mutans, Candida albicans, and enterococci. Results: After a non-brushing period, the full-mouth PI and QPI values between the CH and CHX + CH groups differed significantly. A higher PI score at sampling sites was seen in the CH group, but no significant differences were observed between groups. The S. mutans and C. albicans levels were statistically significant in each group on Days 0 and 4. Differences of C. albicans levels between groups were found to be significant; however, no statistical differences were obtained for S. mutans or enterococci levels among the groups at the various time intervals. Conclusion: We conclude that further investigations are needed to evaluate the potential value of CH as an effective antiplaque mouth rinse. Copyright (C) 2012, Association for Dental Sciences of the Republic of China. Published by Elsevier Taiwan LLC. All rights reserved.WoSScopu