Innovative Drug Discovery and Nanotechnology (Track)




Acyclovir loaded Solid Lipid Nanoparticulate systems – Formulation, characterization and pharmacokinetic evaluation for oral and parenteral routes

Prathima Srinivas
Department of Pharmaceutics, Sri Venkateshwara College of Pharmacy, Hitech city road, Madhapur, Hyderabad-500 081, India

Abstract:

Herpes simplex virus-2 (HSV-2), also known as genital herpes, is one of the most common viral infections in humans. HSV-2 affects 20-25 million people in the United States; with approximately 5, 00,000 new cases reported each year. HSV-2 is characterized by cycles of viral latency and subsequent reactivations that remain with the infected individual for the duration of his or her life. At present, there is no cure for genital herpes. Several anti-viral compounds have been introduced which decrease the frequency of episodes for active lesions. Acyclovir, 9-(2-hydroxyethoxy)-methyl)-guanosine, is the most widely used of these antiviral drugs either in its original form (Zovirax) or as the pro-drug valacyclovir (Valtrex) because it has been shown to be effective in the treatment of HSV-1, HSV-2 and varicella zoster virus. It is widely tolerated in different populations and disease states, and has a high therapeutic index, possibly due to its highly selective biological activity. Prolonged release Solid lipid Nanoparticulate systems of Acyclovir were developed using optimized concentrations of biocompatible lipids like Glyceryl monostearate and lecithin. The formulations were developed for oral and parenteral route of administration. The systems were characterized for Size, Zeta potential and in vitro release. Stable systems were achieved at 5% lipid concentrations. In the oral drug delivery systems, improved stability in the formulation was achieved using minimal amounts of poly methyl methacrylate (PMMA). The size decreased and the size distribution improved with the increase in lipid concentration. The SLN systems showed much slower release than the control systems. In vivo studies were carried out in male rats up to 48 hours to evaluate the pharmacokinetic performance of Acyclovir nanoparticles compared to the conventional control systems. Effect of increased dose on the pharmacokinetics of the drug in the Nanoparticulate form was also investigated. Analysis of the biological samples was performed by HPLC technique and the data was applied to a non-compartmental model. All the pharmacokinetic parameters were determined using Win Nonlin (V 1.1:Pharsight corporation USA) software. The differences in the pharmacokinetic parameters due to various formulations was validated by paired T-test. The difference was considered to be statistically significant at P < 0.05. It was observed that the SLN systems exhibited a slow but prolonged absorption. Increase in the tmax , Cmax and decrease in the clearance of SLN systems was observed when compared to the control systems. As a consequence of extended absorption, improvement in ACV serum availability was also observed. The systems were also as investigated as a Parenteral dosage form for Intravenous administration with enhanced brain delivery and possible escape from the RES by way of tissue distribution studies in male albino Wister bred mice. The drug distribution was studied in brain, heart, lungs, liver, spleen and kidney. The SLN systems were compared with those of the control. The data in SLN systems revealed higher drug levels of about 2.1 times more than the control preparation in the brain. The availability also increased by 1.36 times with the SLN. Higher metabolism and elimination rates of ACV-SLN were observed from Spleen, Liver and Kidney tissues. From the studies performed on the optimized formulation it is evident that Acyclovir can be loaded successfully into Solid Lipid Nanoparticulate systems both for oral and Parenteral route of administration  thereby improving the therapeutic benefit in viral infections.