Synthesis and Characterization of pH-Sensitive Biodegradable Polyurethane for Potential Drug Delivery Applications

To obtain a pH-sensitive multifunctional polyurethane micelle drug carrier, a novel pH-sensitive macrodiol containing acid-cleavable hydrazone linkers, poly(epsilon-caprolactone)-hydrazone-poly(ethylene glycol)-hydrazone-poly(epsilon-caprolactone) diol (PCL-Hyd-PEG-Hyd-PCL), was synthesized and characterized with proton nuclear magnetic resonance spectra (H-1 NMR). A series of pH-sensitive biodegradable polyurethanes (pHPUs) were designed and synthesized using pH-sensitive macrodiol, L-lysine ethyl ester diisocyanate (LDI) and L-lysine derivative tripeptide as chain extender, which can provide an active reaction site for the development of positive target polyurethane micelles for drug delivery. The bulk structures of the prepared polyurethanes were carefully characterized with H-1 NMR, gel permeation chromatograph (GPC), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The polyurethanes could be cleaved in acidic media (pH similar to 4-6) as well as degraded in PBS and enzymatic solution, as demonstrated by H-1 NMR and weight loss, respectively. The cytotoxicity of their degradation products was evaluated using methylthiazoletetrazolium (MTT) assay in vitro, resulting in no apparent inhibition effect on the fibroblasts. These polyurethanes could self-assemble into micelles in aqueous solutions, as verified using dynamic light-scattering (DLS). Our present work provides a new method for the preparation of amphiphilic multiblock polyurethanes with pH-sensitivity and biodegradability. It could be a good candidate as biodegradable multifunctional carrier for active intracellular drug delivery.