Ritonavir loaded surface modified stealth solid lipid nanoparticles: Full factorial design and pharmacokinetic studies

Abstract

This work aims at developing and optimizing the ritonavir loaded stealth solid lipid nanoparticles for parenteral delivery using full factorial design to improve the systemic circulation. The ritonavir loaded stealth solid lipid nanoparticles (SLN) were developed by hot melt homogenization method using tristearin, HSPC and poloxamer 188. The SLNs were evaluated for various physicochemical evaluation parameters such as percent drug content, particle size, zeta potential, % entrapment efficacy and in-vitro drug release studies. The composition of the formulation was finalized by applying constraints (goals) on independent variables (factors) and dependent (response). The Optimization was done based on the criteria of minimum particle size (nm), maximum %EE and maximum zeta potential. The optimized SLN converted into a stealth form using different concentrations of 1,2-distearoyl phosphatidyl ethanolamine-methyl-polyethene glycol conjugate 2000(sodium salt). The drug encapsulation range of stealth solid lipid nanoparticles (SSLN) is between 94.12% and 98.12%. The mean size of particles was found between 126.6 to 146.2 nm. This indicates particles are in uniform distribution. The zeta potential was found in the range of -38.9 to -54.6 mV for stealth solid nanoparticles. The in vivo studies revealed that the drug-loaded SSLN has prolonged circulation time compared to pure ritonavir (PR) when administered to rats through intravenous route. The optimized SSLNs were further evaluated for drug-excipients compatibility, stability and pharmacokinetic studies by Wistar rats. The PEGylation technique improved pharmacokinetic parameters of ritonavir from stealth solid lipid nanoparticles when compared to pure ritonavir. The Paired t-test was used for comparison of the pharmacokinetic parameters. All the statistical assessments have done at a significant level p < 0.05.