No abstract

No abstract

The present study focuses on the development and evaluation of the resveratrol (RV)loaded cationic solid lipid nanoparticles (RV-c-SLNs) for the management of hepatocellular carcinoma (HCC). Materials and Methods: Optimization of formulation was performed using factorial design, and further in vitro drug release, cytotoxicity, biodistribution, in vivo preclinical, and biochemical evaluation were carried out. Results: The optimized formulation exhibited uniform size, homogeneous disparity, positive zeta potential, and stability over 12-week storage at 25°C/60% RH. The in vitro drug release and cytotoxicity study showed 60% drug release within the first 6 hours and comparatively higher cytotoxicity on HepG2 cell line by resveratrol-solid lipid nanoparticle (RV-SLN) as compared to the RV solution. In addition, an anticancer action and biodistribution study on a rat model of HCC showed significant reduction of tumor volume and higher accumulation in the tumor tissue from RV-c-SLN (P<0.01) over RV solution and RV-SLN. Furthermore, RV-c-SLN showed significant downregulation in the levels of pro-inflammatory cytokines and balancing of antioxidant enzymes. Histopathological investigation showed reduced occurrence of hepatic nodules, necrosis formation, infiltration of inflammatory cells, blood vessels inflammation, and cell swelling. Conclusion: Overall, the obtained results construed that RV-c-SLN with improved antitumor activity as clearly evident from in vitro, in vivo, and biochemical investigations.

Chronic hepatitis C virus infection and associated liver diseases represent a major health care burden all over the world. The current standard of care, i.e. peginterferon-alfa (PEG-IFNα) plus ribavirin (RBV) are associated with frequent and sometimes serious adverse effects and contraindications, which further limit their therapeutic efficacy. The approval of first and second generation HCV protease inhibitors represents a major breakthrough in the development of novel direct acting antivirals (DAAs) against different HCV genotypes and establishes a new standard of care for chronically infected HCV genotypes 1 patients. Similarly, next generation protease inhibitors and HCV RNA polymerase inhibitors have shown better pharmacokinetics and pharmacodynamics in terms of broader HCV genotypes coverage, better safety profile, fewer drug interactions and possible once daily administration than first generation direct acting antivirals. The testing of adenovirus-based vector vaccines, which escalates the innate and acquired immune responses against the most conserved regions of the HCV genome in chimpanzees and humans, may be a promising therapeutic approach against HCV infection in coming future. This review article presents up-to-date knowledge and recent developments in HCV therapeutics, insights the shortcomings of current HCV therapies and key lessons from the therapeutic potential of improved anti-HCV treatment strategies.

From 2010, the landscape of hepatitis C therapeutics has been changed rapidly, and today we are standing at a cusp of a pharmacological revolution where highly effective and interferon (IFN)-free direct acting antivirals (DAAs) are already on the market. Such treatment paradigms attain 90-95% sustained virologic response (SVR; undetectable viral load at week 12 or 24 at the end of therapy) rates in treated individuals compared to 50-70% with treatment completion of dual-therapy-pegylated interferon (PEG-IFN) and ribavirin (RBV). As the major goal now for the hepatologists, clinicians, physicians, and health care workers is likely to eradicate hepatitis C infection in parallel to treatment, the demand is for a one-size-fits-all pill that could be prescribed beyond the limitations of hepatitis C genotype, viral load, previous treatment history, advanced hepatic manifestations (fibrosis, cirrhosis) and antiviral drug resistance. Although the new treatment strategies have shown high cure rates in clinical trials, such treatment paradigms are posing dilemmas too in real-world clinical practice. Therapy cost, treatment access to low and middle-income countries, treatment-emergent adverse events, lack of effective viral screening and disease progression simulation models are potential challenges in this prospect. This review article deeply overviews the challenges encountered while surmounting the burden of hepatitis C around the world.