title: The degradation and biocompatibility of pH-sensitive biodegradable polyurethanes for intracellular multifunctional antitumor drug delivery.
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.
authors.affiliation: College of Polymer Science and Engineering, State key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhou
authors.forename: Dong
authors.initials: D
authors.lastname: Liang
authors.forename: Xueling
authors.initials: X
authors.lastname: He
authors.forename: Jiehua
authors.initials: J
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Tan
authors.forename: Jianshu
authors.initials: J
authors.lastname: Li
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.forename: Qun
authors.initials: Q
authors.lastname: Gu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001672:Biocompatible Materials / Q000494:pharmacology*; D001673:Biodegradation, Environmental / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D042541:Intracellular Space / Q000187:drug effects* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008855:Microscopy, Electron, Scanning; D008970:Molecular Weight; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011140:Polyurethanes / Q000138:chemical synthesis / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D011091:Polyesters; D011140:Polyurethanes; C016240:polycaprolactone; D011092:Polyethylene Glycols