title: Poly(omega-pentadecalactone-co-butylene-co-succinate) nanoparticles as biodegradable carriers for camptothecin delivery.
abstract: In this study, we show that degradable particles of a hydrophobic polymer can effectively deliver drugs to tumors after i.v. administration. Free-standing nanoparticles with diameters of 100-300 nm were successfully fabricated from highly hydrophobic, biodegradable poly(omega-pentadecalactone-co-butylene-co-succinate) (PPBS) copolyesters. PPBS copolymers with various compositions (20-80 mol% PDL unit contents) were synthesized via copolymerization of omega-pentadecalactone (PDL), diethyl succinate (DES), and 1,4-butanediol (BD) using Candida antarctica lipase B (CALB) as the catalyst. Camptothecin (CPT, 12-22%) was loaded into PPBS nanoparticles with high encapsulation efficiency (up to 96%) using a modified oil-in-water single emulsion technique. The CPT-loaded nanoparticles had a zeta potential of about -10 mV. PPBS particles were non-toxic in cell culture. Upon encapsulation, the active lactone form of CPT was remarkably stabilized and no lactone-to-carboxylate structural conversion was observed for CPT-loaded PPBS nanoparticles incubated in both phosphate-buffered saline (PBS, pH=7.4) and DMEM medium for at least 24 h. In PBS at 37 degrees C, CPT-loaded PPBS nanoparticles showed a low burst CPT release (20-30%) within the first 24 h followed by a sustained, essentially complete, release of the remaining drug over the subsequent 40 days. Compared to free CPT, CPT-loaded PPBS nanoparticles showed a significant enhancement of cellular uptake, higher cytotoxicity against Lewis lung carcinoma and 9L cell lines in vitro, a longer circulation time, and substantially better antitumor efficacy in vivo. These results demonstrate the potential of PPBS nanoparticles as long-term stable and effective drug delivery systems in cancer therapy.
authors.affiliation: Department of Biomedical Engineering, Yale University, 55 Prospect Street, MEC 414, New Haven, CT 06511-8260, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Zhaozhong
authors.initials: Z
authors.lastname: Jiang
authors.forename: Shengmin
authors.initials: S
authors.lastname: Zhang
authors.forename: W Mark
authors.initials: WM
authors.lastname: Saltzman
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D002166:Camptothecin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000138:chemical synthesis*; D004339:Drug Compounding / Q000379:methods; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008422:Materials Testing; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use / Q000648:ultrastructure*; D009928:Organ Specificity; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D003692:Delayed-Action Preparations; D011091:Polyesters; C545231:poly(omega-pentadecalactone-co-butylene-co-succinate); D002166:Camptothecin