In vitro protein adsorption studies on nevirapine nanosuspensions for HIV/AIDS chemotherapy

• Published in: Nanomedicine Vol. 7; no. 3; pp. 333 - 340
• Main Authors: Shegokar, Ranjita, PhD, Jansch, Mirko, Singh, Kamalinder K., PhD, Müller, Rainer H., PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2011
• Subjects: 2-D PAGE; Acquired Immunodeficiency Syndrome - drug therapy; Adsorption - drug effects; Animals; Biodistribution; Blood Proteins - metabolism; Chemistry, Pharmaceutical; Drug targeting; HIV/AIDS; Human immunodeficiency virus; Humans; Internal Medicine; Nanoparticles - chemistry; Nevirapine - pharmacokinetics; Nevirapine - pharmacology; Nevirapine - therapeutic use; Polyethylene Glycols - chemistry; Polysaccharides - chemistry; Radioactivity; Rats; Suspensions; Tissue Distribution - drug effects; HIV/AIDS; Drug targeting; 2-D PAGE; NS; Biodistribution
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2010.10.012

Abstract Nevirapine is a poorly water-soluble antiretroviral drug. Intravenous nevirapine nanosuspensions (NS) (457 ± 10 nm) were prepared by high-pressure homogenization. NS were surface modified by stabilizer adsorption, e.g., serum albumin, polysaccharide and polyethylene glycol (PEG) 1000. The NS were characterized for mean particle size, particle size distribution and polydispersity index. The targeting potential of the nonmodified and three surface-modified NS to the mononuclear phagocytic system (MPS) cells that serve as potent viral reservoirs was assessed by in vitro protein adsorption studies using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). The adsorption patterns were qualitatively identical, but showed quantitative differences. The relatively adsorbed high amounts of immunoglobulins indicate uptake by liver and spleen, observed quantitative differences (e.g., the amount of dysopsonin albumin and apolipoproteins) can modulate the organ distribution. Controlled in vitro optimization of the protein adsorption by surface modification of the nanocrystals can reduce the number of animals required for in vivo studies and accelerate development of targeted nanoparticles. From the Clinical Editor In this study, intravenous nevirapine (a poorly water-soluble antiretroviral drug) nanosuspensions were prepared by high-pressure homogenization and characterized.