title: Biodegradation, biocompatibility, and drug delivery in poly(ω-pentadecalactone-co-p-dioxanone) copolyesters.
abstract: Poly(ω-pentadecalactone-co-p-dioxanone) [poly(PDL-co-DO)] copolyesters are copolymers of an isodimorphic system, which remain semicrystalline over the whole range of compositions. Here, we evaluated enzymatically synthesized poly(PDL-co-DO) copolymers as new materials for biomedical applications. In vivo experiments using mice, showed that the copolyesters are well tolerated, with tissue responses that are comparable to poly(p-dioxanone). In addition, the copolymers were found to degrade hydrolytically at controlled rates over a period of several months under physiological conditions. The poly(PDL-co-DO) copolymers with up to 69 mol% DO units were successfully transformed to free-standing nanoparticles that are capable of encapsulating an anticancer drug, doxorubicin, or a polynucleotide, siRNA. Drug- or siRNA-loaded nanoparticles exhibited controlled and continuous release of agent over many weeks. In addition, siLUC-encapsulated poly(PDL-co-DO) nanoparticles were active in inhibiting luciferase gene expression in LUC-RKO cells. Because of substantial differences in structure and hydrophobicity between PDL and DO units, poly(PDL-co-DO) biodegradation rate and physical properties can be tuned over a wide range depending on the copolymer composition. Our results demonstrate that the semicrystalline and biodegradable poly(PDL-co-DO) copolyesters are promising biomaterials to serve as drug carriers, as well as potential raw materials for constructing bioabsorbable sutures and other medical devices.
authors.affiliation: Department of Biomedical Engineering, Yale University, 55 Prospect Street, MEC 414, New Haven, CT 06520-8260, 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: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gross
authors.forename: Themis R
authors.initials: TR
authors.lastname: Kyriakides
authors.forename: W Mark
authors.initials: WM
authors.lastname: Saltzman
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry*; D001673:Biodegradation, Environmental / Q000187:drug effects; D004146:Dioxanes / Q000138:chemical synthesis / Q000737:chemistry*; D004317:Doxorubicin / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D005549:Foreign-Body Reaction / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D006868:Hydrolysis / Q000187:drug effects; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008422:Materials Testing; D051379:Mice; D008970:Molecular Weight; D053758:Nanoparticles / Q000648:ultrastructure; D010316:Particle Size; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000378:metabolism; D013095:Spermidine / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D004146:Dioxanes; D011091:Polyesters; D034741:RNA, Small Interfering; C562229:poly(omega-pentadecalactone-co-p-dioxanone); D004317:Doxorubicin; D008156:Luciferases; D013095:Spermidine