Biocompatibility and genotoxicity studies of polyallylamine hydrochloride nanocapsules in rats

Abstract

Polymer nanocapsules have attracted a great deal of interest for drug-delivery and bioimaging applications owing to their functional versatility. The present study focuses on the synthesis, characterisation, biocompatibility and genotoxicity studies of polyallylamine hydrochloride (PAH) nanocapsules for drug-delivery studies. In vitro studies included are haemobiocompatibility studies, cytotoxicity and comet assay in peripheral blood mononuclear cells (PBMCs). Post-intravenous administration of PAH nanocapsules, alteration of haematological parameters, inflammatory marker status, toxicity markers in serum and major organs, RT-PCR, western blotting and histopathological studies of major tissues of rats were evaluated for 30 days. The results of these in vitro studies indicated the biocompatible nature of the PAH nanocapsules at the tested concentrations (1.5 × 10⁵ to 6.0 × 10⁵ capsules per mL). The activity of in vivo toxicity markers, inflammatory marker status like cyclooxygenase (COX), lipooxygenase (LOX), nitric oxide synthase (NOS) and prostaglandin E2 (PGE2) activity, alteration of haematological parameters and RT-PCR analysis of important genes like interleukin-1 beta (IL-1β), monocyte chemotactic protein-1(MCP-1), transforming growth factor beta-1 (TGF-β1), kidney injury molecule-1 (Kim-1), heat shock protein gene (Hsp70-1) and tumor necrosis factor alpha (TNF-α) showed the least changes. Western blotting studies on immunoregulatory proteins like cytokines (IL-8), chemokines (MIP-2) and cell-adhesion molecules (VCAM-1 and ICAM-1) showed the smallest levels of toxicity with PAH nanocapsule interaction. Histopathological studies of important tissues showed almost normal architecture after treatment with PAH nanocapsules throughout the experimental period. The abovementioned results confirm the biocompatibility and non-toxicity of PAH nanocapsules, thus suggesting their potential for in vivo drug-delivery and bioimaging applications.