Poly(anhydride-ester) gemcitabine: Synthesis and particle engineering of a high payload hydrolysable polymeric drug for cancer therapy

Gemcitabine (GMT) is a nucleoside analog used in the treatment of variety solid tumors. GMT was chemically modified with hydrolysable linker, and subsequently incorporated into poly(anhydride-ester) backbone via melt-polymerization, active antimetabolite GMT, thus, becoming repeat unit that makes up this new material, biodegradable polymer. Characterization structure polymeric (polyGMT) revealed incorporation an average 26 molecules per polymer chain, which corresponds to drug loading 58%w/w. The glass transition temperature formed polyGMT determined be 123 °C. PolyGMT engineered nanoparticles (NPs) using dialysis-based method, resulting geometric diameter 206 ± 38 nm. particles are easily dispersible stable aqueous-based media, hydrodynamic 229 28 prepared NPs demonstrate ultra-long release profile due hydrophobic nature as characteristic erosion behavior polymers anhydride-ester bonds. Accelerated vitro studies recovery free upon hydrolysis, biological activity assessed by cytotoxicity assays performed adenocarcinoma human alveolar basal epithelial (A549) highly metastatic murine osteosarcoma (K7M2) cells lines. characteristics polyGMT, including its thermal properties built structure, thus conducive for use preparation delivery systems. Engineered structures can maintain their morphology at ambient physiologically relevant conditions, recovered anhydride ester bonds hydrolyzed. This work innovative first time we ability polymerize engineer chemotherapy. synthetic strategy allows tuning hydrophobicity potentialize behavior, degradation profile, varying linker chemistry. Such controlled very high profiles they may offer opportunities applications malignant neoplasms.