N-Boc-Histidine-Capped PLGA-PEG-PLGA as a Smart Polymer for Drug Delivery Sensitive to Tumor Extracellular pH

A pH-sensitive polymer was synthesized by introducing the N-Boc-histidine to the ends of a PLGA-PEG-PLGA block copolymer. The synthesized polymer was confirmed to be biodegradable and biocompatible, well dissolved in water and forming micelles above the CMC. DOX was employed as a model anticancer drug. In vitro drug release from micelles of N-Boc-histidine-capped PLGA-PEG-PLGA exhibited significant difference between pH = 6.2 and pH = 7.4, whereas DOX release from micelles composed of un-capped virgin polymers was not significantly sensitive to medium pH. Uptake of DOX from micelles of the new polymer into MDA-MB-435 solid tumor cells was also observed, and pH sensitivity was confirmed. Hence, the N-Boc-histidine capped PLGA-PEG-PLGA might be a promising material for tumor targeting.