P糖タンパク質調節機能を持つBrij-グラフト-キトサン共重合体の合成・特性評価およびin vitro検討
Chitosan (CS), a biodegradable natural polysaccharide, holds potential as a nano-carrier material but suffers from limited water solubility. A series of Brij-S20-grafted chitosan copolymers (BCs) with varying grafting degrees were newly synthesized to address this limitation. Water solubility of BCs ranged from 9.13 to 9.54 mg/mL, far exceeding that of unmodified CS (0.32 mg/mL), attributable to disruption of intra- and intermolecular hydrogen bonds and reduced crystallinity. The amphiphilic character of BCs yielded low critical micelle concentrations (0.116–0.376 mg/mL), enabling self-assembly into drug-encapsulating micelles. In MDCK-MDR1 cells, BCs substantially increased intracellular rhodamine-123 accumulation, and confocal microscopy confirmed suppression of P-glycoprotein (Pgp)-mediated drug efflux. These findings suggest BCs are promising polymeric nano-carriers for compounds subject to Pgp-mediated efflux.
Brij grafting disrupts inter- and intramolecular hydrogen bonds in chitosan, improving aqueous solubility. The resulting amphiphilic micelles inhibit P-glycoprotein-mediated efflux, thereby enhancing intracellular drug accumulation in MDR cells.
This is basic research at the cellular or molecular level. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are not recommended).
See also:
https://h2-papers.org/en/papers/30366546