Biocompatible Nanocarrier-Mediated Drug Delivery for the Management of Disease Severity of Experimental Colitis

Abstract

Ulcerative colitis (UC) is a chronic mucosal inflammatory condition that adversely affects colon and rectum. Existing conventional approaches in UC and RA treatment include nonsteroidal antiinflammatory drugs (NSAIDs), mesalazine, corticosteroids, etc. However, these conventional drugs have several inherent limitations like low water solubility, low bioavailability, off-target systemic adverse effects etc., which limit their use in clinics. Nanotechnology based advancements have considerably contributed to the alleviation of inflammation and associated UC disease severity as inflammation greatly contribute in the development of UC. In this thesis, synthesis and characterization of nanoformulation is described for delivery of pharmacological agents such as celecoxib, budesonide etc for targeting inflammation involved in acute experimental colitis. In this thesis, we developed different types of nano-sized delivery systems such as nanostructured lipid carriers (NLCs) and micelles for the delivery of drugs. Importantly, we have used US-FDA approved Generally Recognized as Safe (GRAS) compounds and natural compounds to develop the delivery systems by keeping in mind to develop safe and non-toxic nanoformulation. NLCs were developed by the hot-melt method while nanomicelle were developed by the co-solvent evaporation method. Nanoparticles were characterized for their various physicochemical properties such as particle size, zeta potential, and polydispersity index with dynamic light scattering. Particle shape and surface morphological features were studied with transmission electron microscopy, scanning electron microscopy and atomic force microscopy. Drug loading capacity and drug entrapment efficiency was analyzed with UV-Vis spectroscopy. The developed nanoparticles further used to investigate the cytocompatibility against normal human foreskin fibroblasts (BJ). Furthermore, safety and pharmacological efficacy of these nanoparticles was assessed in-vivo using dextran sodium sulphate (DSS)- induced colitis in Swiss Albino mice models. Results of these studies indicated that nanoparticles possessed favourable physicochemical characteristics in terms of particle size, zeta, polydispersity, shape, surface morphology etc. and delivery of drugs mediated by these, markedly reduced the colitis disease severity in mice model by mitigating the inflammatory biomarkers. Most of the observations in animals, biochemical parameters, and immunohistochemical markers showed a considerably superior degree of restoration by treatment of drug-loaded nanoparticles as compared to free form of drugs alone.