Synthesis, characterization and antiproliferative activity of rapamycin-loaded poly(N-isopropylacrylamide)-based nanogels in vascular smooth muscle cells

Nanogels consist of three-dimensional cross-linked macromolecular polymeric networks which can be loaded with drugs for sustained delivery. In this study, nanogels comprising of poly(N-isopropylacrylamide) (PNIPAM) (NG-1), PNIPAM with poly(ethylene glycol)-maleic anhydride (PEG-MA) (NG-2), and PNIPAM and vinyl pyrrolidone (VP) with PEG-MA (NG-3) were synthesized using simultaneous free-radical cross-linking polymerization in the presence of N,N'-methylenebisacrylamide (cross-linker) and ammonium persulphate/ferrous ammonium sulphate (initiating pair). The chemical constituents present in nanogels were confirmed by spectral analysis (FT-IR, H-1-NMR). The inherent phase transition property of nanogels was determined by measuring lower critical solution temperature (LCST) using UV-Vis spectrophotometer. Rapamycin was selected for loading into nanogels because of our interest in using the drug-loaded nanogel formulations for intravascular drug delivery to prevent post-angioplasty restenosis. Size of nanogels ranged from 25-28 nm in diameter by transmission electron microscopy whereas it ranged from 35-45 nm when determined using dynamic light scattering. Nanogels demonstrated the drug loading capacity (NG-3 > NG-2 > NG-1) and release (NG-1 > NG-2 > NG-3) which varied with the chemical composition of nanogels. NG-1 showed LCST of 38 degrees C whereas the modified nanogels i.e., NG-2 and NG-3 showed 39 degrees C and 55 degrees C, respectively. Nanogels were compatible with vascular smooth muscle cells (VSMCs) and the anti-proliferative effect of the drug loaded nanogels was dose-dependent. Thus, nanogels can be used for intravascular delivery of rapamycin, which is an insoluble drug, and hence can not be administered intravenously.