抄録
Interaction of a hydroxypropylated polyrotaxane with the stratum corneum of hairless rat skin and its increased permeation of indomethacin through the full-thickness skin were examined. Polyrotaxanes are well known as a supramolecular assembly in which many cyclic compounds are threaded onto a liner polymeric chain capped with bulky end-groups. The synthesis of biodegradable polyrotaxanes consists of three steps : the preparation of an inclusion complex consisting of α-cyclodextrins (αCDs) and amino-terminated poly(ethylene glycol) (PEG), the introduction of L-phenylalanine (L-Phe) at each complex terminal via peptide linkages, and the hydroxypropylation of αCDs in the polyrotaxanes. The hydroxypropylation of αCDs improved the solubility of the polyrotaxanes in PBS, pH7.4. A decrease in the bound water content was observed at the stratum corneum treated by hydroxypropylated (HP-) polyrotaxanes. Further, enhanced permeation of indomethacin through the skin was observed by the treatment of HP-polyrotaxanes. These results suggest that a supramolecular structure of the polyrotaxane caused the exchange of water in polar lipids or some extraction of polar lipids from the stratum corneum to enhance indomethacin permeation. Further, such enhanced effect of the polyrotaxane on indomethacin permeation was also observed when the skin was treated from dermis side. This result suggests a possibility that the HP-polyrotaxane penetrates into the stratum corneum to enhance indomethacin permeation. The polyrotaxane can be dissociated into PEG and αCDs by degradation of the terminal moiety. Therefore, it is concluded that a feasible design of polyrotaxane terminals degradable at subcutaneous tissues provides excellent properties as an enhancer with a passive safety system.
