Injectable block copolymer hydrogels for sustained release of a PEGylated drug

• Published in: International journal of pharmaceutics Vol. 348; no. 1; pp. 95 - 106
• Main Authors: Yu, Lin, Chang, Guang Tao, Zhang, Huan, Ding, Jian Dong
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 04.02.2008; Elsevier
• Subjects: Animals; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - pharmacokinetics; Antineoplastic Agents, Phytogenic - therapeutic use; Biological and medical sciences; Biological Availability; Block copolymer; Camptothecin (CPT); Camptothecin - administration & dosage; Camptothecin - pharmacokinetics; Camptothecin - therapeutic use; Delayed-Action Preparations - chemical synthesis; Delayed-Action Preparations - chemistry; Drug Delivery Systems - methods; General pharmacology; Glycolates - chemistry; Hydrogels - chemistry; Injectable hydrogel; Injections, Subcutaneous; Kinetics; Lactic Acid; Medical sciences; Mice; Mice, Inbred Strains; Microscopy, Electron, Transmission; PEGylation; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phase Transition; Polyethylene Glycols - chemistry; Polyglycolic Acid; Sarcoma 180 - drug therapy; Sarcoma 180 - pathology; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Spectroscopy, Fourier Transform Infrared; Sustained release; Transition Temperature; Viscosity; Sustained release; PEGylation; Injectable hydrogel; Block copolymer; Camptothecin (CPT); Antineoplastic agent; Drug; Pharmaceutical technology; Enzyme; Controlled release form; DNA topoisomerase; Enzyme inhibitor; Colloidal gel; Alkaloid; Isomerases; Dosage form; Hydrogel; Pegylated form; Topoisomerase I inhibitor
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2007.07.026

The paper employs the spontaneous physical gelling property of a biodegradable polymer in water to prepare an injectable sustained release carrier for a PEGylated drug. A series of thermogelling PLGA–PEG–PLGA triblock copolymers were synthesized. The PEGylated camptothecin (CPT) was also prepared and employed as the model of a PEGylated drug, and the solubility of this hydrophobic drug was significantly enhanced to over 150 mg/mL. The model drug was completely entrapped into the polymeric hydrogel, and the sustained release lasted for 1 month. The mechanism of the sustained release was diffusion-controlled at the first stage and then was the combination of diffusion and degradation at the late stage. In vivo anti-tumor tests in mice further confirmed the efficacy of the model PEGylated drug released from the hydrogel. This work also revealed the specificity of the PEGylated drug in such a kind of carrier systems by decreasing the critical gelling temperature and increasing the viscosity of the sol. Due to the very convenient drug formulation and highly tunable release rate, an injectable carrier platform for PEGylated drugs is thus set up.