Formulation, Optimization, and Invitro Characterization of Lipid-Based Nanoparticles for Effective Delivery to The Liver

Abstract

- Chronic liver disorders are the major causes of illness and mortality worldwide. Patients with chronic liver diseases have a greater chance of developing cirrhosis, hepatocellular carcinoma, progressive liver fibrosis, and subsequently liver failure. Currently there are no effective treatments available for patients with the various kinds of liver diseases. The use of nanotechnology is considered a rapidly growing field of interest for the safe and targeted delivery of insufficiently water-insoluble hepatoprotective drugs. Therefore, the nanoparticle combination improves bioavailability and plasma stability of drugs with poor aqueous solubility. Thus, this study aims at developing chemically and physically stable Fenretinide loaded solid lipid nanoparticles (FEN-SLNs) for successful delivery to the liver. The nanoencapsulation of FEN in Gelucire-based, surfactant-free SLNs was developed. SLNs were characterized in terms of physicochemical properties, surface morphology, drug loading, release behavior as well as in vivo biodistribution study. The results showed that adopting hot homogenization method for preparation of FEN loaded solid lipid nanoparticles using Gelucire 50/13 and Precirol provided chemically and physically stable FEN-SLNs. Further, the optimized FEN-SLNs has particle size 298.3 ± 2.54 and PDI 0.3 with negative zeta potential -15.2 ± 3.61 mV, and Entrapment efficiency exceeding 92%. Furthermore, in vitro release experiment ensured sustained release of FEN over > 24 h with no signs of degradation. In addition, TEM photomicrographs showed spherical particles. Noteworthy, the in vivo biodistribution results showed that fluorescently labeled SLNs retained in the liver for 8h with diminished migration to the other organs unlike the free dye. In conclusion the study highlights the effective encapsulation of FEN and effective delivery to the liver.