title: Amphiphilic block co-polyesters bearing pendant cyclic ketal groups as nanocarriers for controlled release of camptothecin.
abstract: Amphiphilic block co-polymers consisting of hydrophilic poly(ethylene glycol) and hydrophobic polyester bearing pendent cyclic ketals were synthesized by ring-opening co-polymerization of ε-caprolactone (CL) and 1,4,8-trioxaspiro-[4,6]-9-undecanone (TSU) using α-hydroxyl, ω-methoxy, poly(ethylene glycol) as the initiator and stannous octoate as the catalyst. Compositional analyses indicate that TSU was randomly distributed in the hydrophobic blocks. When the TSU content in the co-polymers increased, the polymer crystallinity decreased progressively and the glass transition temperature increased accordingly. The hydrophobic, anticancer drug, camptothecin (CPT), was successfully encapsulated in the block copolymer nanoparticles. The CPT encapsulation efficiency and release kinetics were strongly dependent on the co-polymer composition and crystallinity. CPT release from nanoparticles constructed from co-polymers containing 0, 39 and 100 mol% TSU in the hydrophobic block followed the same trend, with an initial burst of approx. 40% within one day followed by a moderate and slow release lasting up to 7 days. At a TSU content of 14 mol%, CPT was released in a continuous and controlled fashion with a reduced initial burst and a 73% cumulative release by day 7. The in vitro cytoxicity assay showed that the blank nanoparticles were not toxic to the cultured bone metastatic prostate cancer cells (C4-2B). Compared to the free drug, the encapsulated CPT was more effective in inducing apoptotic responses in C4-2B cells. Modulating the physical characteristics of the amphiphilic co-polymers via co-polymerization offers a facile method for controlling the bioavailability of anticancer drugs, ultimately increasing effectiveness and minimizing toxicity.
authors.affiliation: a Department of Materials Science and Engineering, 201 DuPont Hall, Delaware Biotechnology Institute, University of Delaware, Newark, DE 19716, USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wang
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Gurski
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhong
authors.forename: Xian
authors.initials: X
authors.lastname: Xu
authors.forename: Darrin J
authors.initials: DJ
authors.lastname: Pochan
authors.forename: Mary C
authors.initials: MC
authors.lastname: Farach-Carson
authors.forename: Xinqiao
authors.initials: X
authors.lastname: Jia
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000188:drug therapy / Q000503:physiopathology / Q000556:secondary; D002166:Camptothecin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002208:Caproates / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry; D005898:Glass / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D007783:Lactones / Q000737:chemistry; D008297:Male; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000737:chemistry; D044366:Transition Temperature
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002208:Caproates; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007783:Lactones; D011091:Polyesters; D013501:Surface-Active Agents; D011092:Polyethylene Glycols; C121056:caprolactone; D002166:Camptothecin