title: Feasibility of poly (ϵ-caprolactone-co-DL-lactide) as a biodegradable material for in situ forming implants: evaluation of drug release and in vivo degradation.
abstract: The purpose of this study was to evaluate the technical feasibility of poly (ϵ-caprolactone-co-DL-lactide), P (CL/DL-LA), for injectable in situ forming implants (ISFI). The ISFI was prepared by dissolving P (CL/DL-LA) in N-methyl-2-pyrrolidone (NMP), and Testosterone undecanoate (TU) was used as model drug. The effect of various polymer concentrations, molecular weights (Mws) and drug loads on the drug release from the TU-loaded ISFI systems was investigated in vitro. The release of TU-loaded ISFI was also evaluated in rats. In addition, a subcutaneous rabbit model was used to evaluate the degradation and foreign-body reaction of P (CL/DL-LA) ISFI. The use of higher concentration of P (CL/DL-LA) with higher molecule weight and larger CL:DL-LA monomer ratio for the TU-loaded ISFI gave a slower drug release. The ISFI of 80/20 P (CL/DL-LA) (Mw 61 753):NMP 20:80 with 16% TU formulation increased serum testosterone levels in rats over a period of three months. The in vivo degradation and biocompatibility study of ISFI shows that P (CL/DL-LA) degrades by a process of bulk degradation and that the foreign-body reaction of this biomaterial is relatively mild. In summary, our investigations demonstrate that in situ parenteral drug delivery systems can be obtained from P (CL/DL-LA) solutions.
authors: Liaoning Research Institute of Family Planning , Shenyang , People's Republic of China.
authors: Xiaowei
authors: X
authors: Zhang
authors: Chong
authors: C
authors: Zhang
authors: Wei
authors: W
authors: Zhang
authors: Shu
authors: S
authors: Meng
authors: Danhua
authors: D
authors: Liu
authors: Ping
authors: P
authors: Wang
authors: Jing
authors: J
authors: Guo
authors: Jianxin
authors: J
authors: Li
authors: Yanmin
authors: Y
authors: Guan
authors: Dan
authors: D
authors: Yang
mesh_terms: D020341:Absorbable Implants / Q000009:adverse effects; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005240:Feasibility Studies; D005549:Foreign-Body Reaction / Q000209:etiology / Q000473:pathology; D066298:In Vitro Techniques; D007279:Injections, Subcutaneous; D008297:Male; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D011091:Polyesters / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics
chemical_list: D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D011091:Polyesters; D013739:Testosterone; C062968:lactide-caprolactone copolymer; C010792:testosterone undecanoate
keywords: Biocompatibility; biodegradable polymers; controlled delivery; in situ forming implants; poly (ϵ-caprolactone-co-DL-lactide); testosterone undecanoate