Abstract
pH-responsive docetaxel-conjugated poly (lactic acid) (PLA)–polyethyleneglycol (PEG) micellar formulation was synthesized via acid labile hydrazone linkage. Levulinic acid (LEV) was used as a linker between docetaxel (DTX) and hydrazine. Targeted delivery of DTX was achieved by conjugation of folate to PEG segment. The DTX conjugated polymeric micelles were about 181nm in diameter and their critical micelle concentration was 5.18μg/ml. DTX was released from micelles in a pH-dependent manner. The results showed a significant difference in DTX release from polymeric micelles at pH 5.0 and pH 7.4. Cytotoxicity assays using methyl tetrazolium (MTT), neutral red (NR) and lactate dehydrogenase (LDH) demonstrated a decreased cytotoxic activity of the drug containing nanoconjugate compared with free DTX that appears to be contributed to the sustained release of drug from micelles. Based on these results, it is expected that this pH-responsive nanoconjugate is promising as a useful carrier for targeted delivery of anticancer agents.
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