The degradation and biocompatibility of pH-sensitive biodegradable polyurethanes for intracellular multifunctional antitumor drug delivery

• Published in: Biomaterials Vol. 33; no. 9; pp. 2734 - 2745
• Main Authors: Zhou, Lijuan, Liang, Dong, He, Xueling, Li, Jiehua, Tan, Hong, Li, Jianshu, Fu, Qiang, Gu, Qun
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.03.2012
• Subjects: Advanced Basic Science; Animals; Antineoplastic Agents - pharmacology; Biocompatibility; Biocompatible Materials - pharmacology; Biodegradation; Biodegradation, Environmental - drug effects; Dentistry; Drug delivery; Drug Delivery Systems - methods; Female; Hydrogen-Ion Concentration - drug effects; Intracellular Space - drug effects; Intracellular Space - metabolism; Magnetic Resonance Spectroscopy; Male; Microscopy, Electron, Scanning; Molecular Weight; pH-sensitive polyurethanes; Polyesters - chemistry; Polyethylene Glycols - chemistry; Polyurethanes - chemical synthesis; Polyurethanes - chemistry; Rats; Rats, Sprague-Dawley; Biodegradation; pH-sensitive polyurethanes; Biocompatibility; Drug delivery
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2011.11.009

Abstract To obtain controllable stepwise biodegradable polymer for multifunctional antitumor drug carriers, pH-sensitive biodegradable polyurethanes were firstly synthesized using poly(ϵ-caprolactone) (PCL) and pH-sensitive poly(ϵ-caprolactone)–hydrazone–poly(ethylene glycol)–hydrazone–poly(ϵ-caprolactone) macrodiol (PCLH) as soft segment; l -lysine ethyl ester diisocyanate (LDI), l -lysine derivative tripeptide and 1,4-butandiol (BDO) as hard segment; and hydrazone-linked methoxyl-poly(ethylene glycol)(m-PEG-Hyd) as end-capper. Then, an extensive degradation process of the prepared pH-sensitive polyurethanes was investigated in vitro with proton nuclear magnetic resonance spectra (1 H NMR), gel permeation chromatograph (GPC), scanning electron microscopy (SEM), and weight loss. It was found that the degradation of these polyurethanes occurred via the random hydrolytic ester cleavage along the PCL segments close to PEG segments in enzymatic solutions while the hydrazone bond in the polymer chain was more easily cleaved in acidic media, which was accelerated with decreasing pH value. Furthermore, the biocompatibility in vivo was evaluated in an intramuscular implantation model on Sprague–Dawley rats, using SEM and light microscopy. The result showed that the prepared polyurethanes can be easily degraded and the degradation products do not induce any adverse response from surrounding muscle tissues. Our work suggests that the prepared pH-sensitive polyurethanes could be promising materials as controllable biodegradable and non-cyctotoxic multifunctional carriers for active intracellular drug delivery.