Stereocomplex Prodrugs of Oligo(lactic acid) _n-Gemcitabine in Poly(ethylene glycol)- block-poly(d,l-lactic acid) Micelles for Improved Physical Stability and Enhanced Antitumor Efficacy.

ABSTRACT: Herein we demonstrate the formation of stereocomplex prodrugs of oligo(l-lactic acid) _n-gemcitabine (o(LLA) _n-GEM) and oligo(d-lactic acid) _n-gemcitabine (o(DLA) _n-GEM) for stable incorporation in poly(ethylene glycol)- block-poly(d,l-lactic acid) (PEG- b-PLA) micelles. O(LLA) _n or o(DLA) _n was attached at the amino group (4-( N)) of GEM via an amide linkage. When n = 10, a 1:1 mixture of o(LLA)₁₀-GEM and o(DLA)₁₀-GEM (o(L+DLA)₁₀-GEM) was able to form a stereocomplex with a distinctive crystalline pattern. Degradation of o(L+DLA)₁₀-GEM was driven by both backbiting conversion and esterase contribution, generating primarily o(L+DLA)₁-GEM and GEM. O(L+DLA)₁₀-GEM

SUBMITTER: Tam YT 

PROVIDER: S-EPMC6071312 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature