title: Polymeric micelles for pH-responsive delivery of cisplatin.
abstract: Methoxy poly(ethylene oxide)-block-poly-(α-carboxylate-ε-caprolactone) (PEO-b-PCCL) was used to develop pH-responsive polymeric micelles for the delivery of cisplatin (CDDP). Micelles were prepared through complexation of CDDP with the pendant carboxyl groups on the poly(ε-caprolactone) core, perhaps through coordinate bonding. The obtained micelles were characterized using dynamic light scattering (DLS) measurement for size and stability. The in vitro release of CDDP at different pHs (7.4, 6.0 and 5.0) was evaluated. The in vitro cell uptake as well as cytotoxicity of developed micelles against two breast cancer cell lines, i.e. MDA-MB-435 and MDA-MB-231, were also assessed and compared to free CDDP as control. DLS results showed PEO-b-PCCL to form stable micelles with an average diameter of <50 nm upon complexation with CDDP. Developed polymeric micelles were capable of slowly releasing CDDP in physiological pH. However, CDDP release from polymeric micelles was triggered upon exposure to electrolytes and/or acidic pHs mimicking that of extracellular tumor microenvironment or intracellular organelles. Consistent with the slow release of CDDP from its polymeric micellar formulation, polymeric micellar CDDP exhibited lower cytotoxicity and CDDP intracellular uptake compared to free drug. The results indicate a great potential for the developed formulation in platinum therapy of breast cancer.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences and.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Shahin
authors.forename: Nazila
authors.initials: N
authors.lastname: Safaei-Nikouei
authors.forename: Afsaneh
authors.initials: A
authors.lastname: Lavasanifar
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000494:pharmacology; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D065546:Drug Liberation; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008027:Light; D008823:Micelles; D010316:Particle Size; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D012542:Scattering, Radiation; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; C000595636:methoxy poly(ethylene oxide)-block-poly(alpha-carboxylate-epsilon-caprolactone); D011092:Polyethylene Glycols; D002945:Cisplatin
keywords: Breast cancer; cell uptake; cisplatin; cytotoxicity; pH sensitive; polymeric micelles