mPEG-CS-modified flexible liposomes-reinforced thermosensitive sol-gel reversible hydrogels for ocular delivery of multiple drugs with enhanced synergism.

Non-invasive drug delivery offers a safe treatment while improving patient compliance. However, due to the particular physiological structure of the ocular, long-term retention and sustained drug release of the drug delivery system is crucial. Herein, this study aimed to design mPEG-CS-modified flexible liposomes-reinforced thermosensitive sol-gel reversible hydrogels (mPEG-CS-FL-TSG) for the delivery of astragaloside IV (AS-IV) and tetramethylpyrazine (TMP) to treat age-related macular degeneration. In vitro biological properties of mPEG-CS-FL and mPEG-CS-FL-TSG showed that they could be successfully taken up by ARPE-19 cells, and the uptake rate of mPEG-CS-FL-TSG was higher. Not only that, the release rate of mPEG-CS-FL-TSG was slower. More significantly, the results showed that the cytotoxicity of mPEG-CS-FL-TSG was lower than that of mPEG-CS-FL. In vivo result revealed that the drug delivery system could prominently enhance the ocular bioavailability of AS-IV and TMP, which is the enhanced synergism of well-permeable liposome and slow-releasing hydrogel. In summary, the mPEG-CS-FL-TSG can compensate for the short retention time and sudden release of liposome, as well as the low drug penetration of hydrogel, in order to show great promise in the non-invasive delivery of multiple drugs for the treatment of posterior ocular diseases.