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

Abstract Novel comb-shaped amphiphilic copolymers based on methoxy poly(ethylene glycol)- b -[poly(e-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 unitsself-assemble into a core-shell structure in an aqueous solution. Critical aggregation concentrations range within 5.6 × 10 −3 –7.0 × 10 −2 mg/mL in double deionized water and 8.9 × 10 −3 –7.0 × 10 −2 mg/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 220–246 nm, slightly dependent on pMAA length. However, the cisplatin-loaded MPCL- g -pMAAs particles have average hydrodynamic diameters of 263–412 nm owing to increasing drug loading efficiency with increase in pMAA length. Nevertheless, the MPCL- g -pMAA with the least number of MAA repeating unitshows 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.