pH-responsive targeted and controlled doxorubicin delivery using hyaluronic acid nanocarriers

• Sustained drug delivery system is proposed.
• Nanogels based on biocompatible hyaluronic acid-pluronic polymers.
• Effective anticancer activity via sustained delivery of doxorubicin.

Biocompatible nanogels were prepared using thiol modified hyaluronic acid and diacrylated pluronic F127 polymer. A simple Michael type addition reaction of activated thiol groups on acrylate moiety lead to the formation of these nanogels, which were further effectively fabricated with an anticancer drug for evaluating sustained drug release approach. Nanogels prepared were of 150 nm in diameter with a narrow size distribution pattern. DOX released from these nanogels showed a slow and sustained release at acidic pH 5.0 as compared to minimal release at physiological pH 7.4. Cytotoxicity data revealed the higher efficiency of DOX loaded nanogels as compared to free DOX in Hela cell lines. Cellular uptake images supported the cytotoxicity data and displayed DOX intercalation at nuclear level of cells. The sustained drug delivery system showed DOX release after 24 h and continued thereafter without affecting normal cells. Based on these findings, such nanogel system may be useful for delivering anticancer drug without hampering their toxicity value over longer durations and reducing the total dose amount in anticancer therapy.

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