Evaluation of Amphiphilic Chitosan Hydrogel as Topical Delivery Carrier of Magnesium Ascorbyl Phosphate

• Main Authors: Yan-ling Huang, 黃彥凌
• Other Authors: J.-C. Tsai
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/10691378103537314923

碩士 === 國立成功大學 === 臨床藥學研究所 === 96 === Chitosan, a polysaccharide, is obtained by partial deacetylation of chitin, the second most abundant polymer. It has been receiving a great deal of interest for medical and pharmaceutical applications due to its intrinsic properties, including biocompatibility, biodegradability, non-antigenicity and so on. However, the solubility of chitosan is very poor. Many works have attempted to modify its structure and chemistry. Magnesium ascorbyl phosphate (MAP), an ascorbic acid derivative, is rapidly converted to ascorbic acid by phosphatases in the skin. Studies have demonstrated MAP was equivalent to ascorbic acid in stimulating collagen synthesis in dermal fibroblasts. The objectives of the studies were to modify the water-soluble chitosan derivative – glycol chitosan, by the use of pendant hydrophobic groups to achieve non-covalent cross-linking with lauric and palmitic acid, and to evaluate the potential of the amphiphilic hydrogels as topical delivery carrier for the hydrophilic model compound, MAP. The levels of lauroylation and palmitoylation in the polymers, as determined by proton neutron magnetic resonance spectroscopy, were 16.3 ± 2.5 % and 13.4 ± 1.8%, respectively. The molecular structures of the amphiphilic polymers were characterized by their FT-IR spectra. They were also shown to be highly stable at high-humidity environment. The viscosity of the polymer was higher with palmitoyl cross-linkage, and hydration was better under neutral than acidic conditions. The effects of amphiphilic glycol chitosan on the skin penetration of MAP were evaluated through nude mice skin. MAP release from the hydrogel was significantly decreased with increasing amount of amphiphilic glycol chitosan in the formulations. Regardless of the addition of 10% ethyl alcohol, skin penetration of MAP prepared in amphiphilic glycol chitosan was effectively increased. In aqueous vehicle, MAP flux was increased 2.96 and 1.6 fold with 1% GCL and GCP, respectively, while in 10% ethanol, it was decreased to 0.96 and 0.79 fold. Nevertheless, skin flux of MAP was increased when the amount of hydrogel was increased. The increase of skin penetration was more prominent with GCL, which is cross-linked with the shorter chain length of lauric acid, than GCP. In conclusion, the studies demonstrated physically cross-linked chitosans with lauric and palmitic acids increased the skin penetration of MAP. Both GCL and GCP can potentially be applied as topical delivery carriers to improve percutaneous absorption of hydrophilic drugs.