Development of novel pH-responsive block copolymer micelles for drug targeting

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The pH responsive polymeric micelles functionalized with acid-cleavable hydrazone linkers were prepared and characterized in this study. This micellar drug carrier from amphiphilic block copolymer polyethylene glycol)-poly(aspartate hydrazide adriamycin) [PEG-p(Asp-Hyd-ADR)] showed a good pH responsive drug release profile in various pH conditions. The size of micelles was confirmed to be tens of nm in diameter by dynamic light scattering (DLS) measurement.The anticancer drug. Adiramycin(ADR), was bound to the polymer backbone through an acid-labile Schiff base linkage between me carbonyl at the C13 of ADR and the hydrazide group attached to the p(Asp) segment of PEG-PBLA block copolymer. A drag binding linker, Schiff base linkage, was designed to be hydrolytically cleaved in the lysosomal compartment of the cell, where local pH is one order of magnitude lower (pH 4.5-5.5) than physiological condition (pH 7.4) so the Schiff base bond can be cleaved most efficiently.The pH responsive pr … More operty of the micelles was characterized by reversed-phase high performance liquid chromatography (HPLC). In lowered pH conditions (pH 4.5〜5.5) corresponding lysosomal compartments, ADR was successfully released from the micelles within 10h while it remained stable at pH 7.4 over 80hr. No drug release at pH 7.4 for a long period reflects the possibility of minimal systemic leakage and the rapid drug release in acidic conditions could be an advantage from the standpoint of site-specific drug delivery due to the preferential drug release at the solid tumor.Disintegration of the micelles was recognized monitoring the decrease of relative light scattering intensity by static light scattering (SLS) measurement. The micelles were considered to dissociate into free polymer chains by losing the driving force of micellization, hydrophobic interaction in the micellar core as drugs released.A significant figure of this neo-functional pH responsive polymeric micelle indicated the promising solution as a drug carrier not only to reduce die side-effects by improving the intracellular localization of ADR but also to circumvent the multi-drug resistant (MDR) problems in cancer chemotherapy. Less