Length effect of methoxy poly(ethylene oxide)-b-[poly(ε-caprolactone)-g-poly(methacrylic acid)] copolymers on cisplatin delivery

A novel comb-shape amphiphilic copolymer of mPEG-b-[PCL-g-pMAA] was constructed to chelate cisplatin for passive drug targeting into cancerous cells. [Display omitted] •A comb-shape amphiphilic copolymer, MPEG-PCL-pMAA, was constructed.•Zinc ethyl β-diiminate was adopted for the ROP reaction of MPCL-Br.•MPEG-PCL-pMAA particles were utilized to coordinate cisplatin for chemotherapy.•MPEG-PCL-pMAA particles can be utilized to a co-delivery system of two drugs. Novel comb-shaped amphiphilic copolymers based on methoxy poly(ethylene glycol)-b-[poly(ε-caprolactone)-g-poly(methacrylic acid)] (MPCL-g-pMAA), were synthesized via ring opening polymerization (ROP) and atom transfer radical polymerization (ATRP) for drug delivery systems. MPCL-g-pMAAs with various MAA repeating units self-assemble into a core-shell structure in an aqueous solution. Critical aggregation concentrations range within 5.6×10−3–7.0×10−2mg/mL in double deionized water and 8.9×10−3–7.0×10−2mg/mL in phosphate buffered saline of pH 7.4, decreasing with increase in pMAA length. The carboxylic groups of MPCL-g-pMAAs were utilized to coordinate cisplatin, forming polymer-metal complexes for chemotherapy. The average hydrodynamic diameters of particles are within 220–246nm, slightly dependent on pMAA length. However, the cisplatin-loaded MPCL-g-pMAAs particles have average hydrodynamic diameters of 263–412nm owing to increasing drug loading efficiency with increase in pMAA length. Nevertheless, the MPCL-g-pMAA with the least number of MAA repeating unit shows the fastest drug release rate as well as the highest cytotoxicity against CRL-5802 cells. The cellular uptake of MPCL-g-pMAA particles, involving mainly clathrin-mediated endocytosis, increases with incubation time. MPCL-g-pMAA particles are non-cytotoxic to CRL-5802 cells but the cisplatin-loaded MPCL-g-pMAA particles show profound cell-killing ability. The MPCL-g-pMAA is a potential carrier for drug delivery systems.