Visualization of the penetrative and mucoadhesive properties of chitosan and chitosan-coated liposomes through the rat intestine.

The objectives of this study were to observe the penetrative and mucoadhesive behavior of polymer-coated liposomes into the intestinal mucosa of rats. Chitosan (CS) and negatively charged liposomes were chosen as model polymer-coated liposomes. In order to observe their behavior, chitosan was labeled with Fluorescence Isothiocyanate (FITC) via chemical reaction at the isothiocyanate group of FITC and the primary amino group of chitosan; the liposomes (Lips) were marked by incorporation of DiI into the liposomal formulation. FITC-labeled chitosan (FITC-CS), Non-Lips, and FITC-labeled CS-coated Liposomes (FITC-CS-Lips) were intragastrically administered into male Wistar rats, and the behavior of the molecules was subsequently visualized by CLSM (Confocal Laser Scanning Microscopy). The results demonstrated that the chitosan molecules themselves, as well as the liposomes, could penetrate across the intestinal mucosa. Moreover, the CLSM images demonstrated a lack of separation of the chitosan molecules from the surface of the liposomes after the administration of chitosan-coated liposomes.

Properties of liposomes coated with hydrophobically modified chitosan in oral liposomal drug delivery.

Chitosan (CS) has been widely used as an adhesive coating polymer for oral liposomal drug delivery systems because of its adhesive properties on mucous layers. The coating mechanism or interaction of chitosan and liposomes or mucin mainly depends on electrostatic forces. Thus, to enhance the adhesive properties of chitosan, a hydrophobically modified chitosan, i.e., dodecylated chitosan (DC), was synthesized. BIACORE results showed that both CS and DC could interact with mucin. Differences in sensorgram patterns between chitosan-mucin and dodecylated chitosan-mucin were observed and tentatively attributed to differences in binding kinetics. The zeta potential of dodecylated chitosan-coated liposomes (DC-Lip) showed positive values in both liposomal formulations, i.e., negatively charged and neutral-charge liposomes. These results indicated that DC could be considered a more suitable polymer for coating neutral-charge liposomes than CS because the hydrophobic side chain of DC inserts itself into the lipid bilayer of liposomes. Moreover, CS seemed to be less effective in the coating of a neutral-charge liposome because of the low positive values of its zeta potential. CS provided solely electrostatic forces when used for coating liposomes while DC provided electrostatic and hydrophobic forces due to the long alkyl chain in its backbone. Confocal Laser Scanning Microscopy (CLSM) images indicated that both chitosan-coated liposomes (CS-Lip) and DC-Lip could adhere to and penetrate through the small intestine of rats after oral administration. The pharmacological results showed that DC-Lip had a greater effect in decreasing blood calcium concentration during the first 12 h compared with CS-Lip. Therefore, it can be concluded that dodecylated chitosan can be useful in designing oral liposomal drug delivery systems.

Cholesterol-bile salt vesicles as potential delivery vehicles for drug and vaccine delivery.

The aim of this study was to further investigate the interactions between cholesterol (CH) and mixed bile salts (BS) (sodium cholate and sodium deoxycholate) and their suitability for drug and vaccine delivery. Insulin was used as a model protein to assess the ability of CH:BS vesicles to entrap a therapeutically relevant macromolecule. The association of protein (FITC-insulin) with the CH:BS structure was confirmed with fluorescence microscopy, and the overall morphology of the vesicles was examined with atomic force microscopy (AFM). Results demonstrate that the nature of the vesicles formed between CH and BS is dependent not only on the concentration of BS but also on the increasing CH concentration leading to CH crystal formation.