Improved Body Distribution of¹⁴C-labelled AZT bound to Nanoparticles in Rats determined by Radioluminography

Abstract

The objective of the present study is to visualize differences in the body distribution between radiolabelled AZT bound to nanoparticles and a control solution. Polyhexylcyanoacrylate nanoparticles were manufactured by emulsion polymerization in the presence of AZT and an ionic emulsifier, bis(2-ethylhexyl) sulfosuccinate sodium. The AZT-control solution was equally prepared, but contained no monomer. The two preparations were administered either by i.v. injection or perorally by gavage. After determined time points the animals were sacrificed using carbon dioxide. The cadavers were shock-frozen in cellulose gel and cut into slices using a cryomicrotome. The tissue cross sections were fixed on an adhesive tape and then were freeze dried. The quantification of the radioactive AZT in the different organs and tissues was performed by radioluminography, and the images were generated on a computer. After i.v. injection of AZT-nanoparticles, a high amount of the AZT label was found in the organs belonging to the reticuloendothelial system. In these organs the radioactivity was inhomogeneously distributed showing that the uptake of the particle-associated radioactivity depended on the type of the cells located in the organs and was consistent with uptake by macrophages. The highest radioactivities were found in the GI-tract and in the liver. A difference in the elimination pathway between AZT-control solution and AZT bound to nanoparticles also was visible on the images. Similar results were obtained after oral administration. Of course, with the latter route a larger portion of AZT remained in the GI-tract especially after administration of nanoparticle-bound drug. These results confirmed those obtained by a classically performed quantitative whole body distribution study using liquid scintillation. This demonstrates that radioluminography is a useful method to study the organ distribution of drugs bound to nanoparticles.

Preparation, characterization, and in vivo pharmacokinetics of nanostructured lipid carriers loaded with oleanolic acid and gentiopicrin

“…15 Therefore, nanoparticles in the relatively small size range of 100-150 nm are desirable when targeting agents to the liver. The main aim of this study was to achieve optimal incorporation of gentiopicrin and oleanolic acid in NLCs using a film-ultrasonic method to enhance entrapment efficiency and a central composite design for the response surface.…”

Nanotechnology Based Targeted Drug Delivery: Current Status and Future Prospects for Drug Development

“…Use of this carrier system, when compared with aqueous drug solution resulted in higher of the drug levels in the Peyer's patches. In another study, polyhexylcyanoacrylate nanoparticles were employed for the delivery of zidovudine (Lobenberg et al, 1998), thus improving its bioavailability. In a distinct experiment, PLGA nanoparticles containing multiple antiretroviral drugs, i.e ritonavir, lopinavir, and efavirenz were formulated and results showed that drugs could be detected in peripheral blood mononuclear cells in vitro for 28 days (Destache et al, 2009).…”

“…In a distinct experiment, PLGA nanoparticles containing multiple antiretroviral drugs, i.e ritonavir, lopinavir, and efavirenz were formulated and results showed that drugs could be detected in peripheral blood mononuclear cells in vitro for 28 days (Destache et al, 2009). In a study with zidovudine-loaded poly(isohexyl cyanate) nanoparticles, zidovudine was accumulated in the cells of the reticuloendothelial system (Lobenberg et al, 1998). Poly(epsilon-caprolactone) nanoparticles loaded with saquinavir were also successfully used for targeting the phagocytic mononuclear system by modifying the surface of the nanoparticles (Shah & Amiji, 2006).…”

Preparation and characterization of nanoparticles of carboxymethyl cellulose acetate butyrate containing acyclovir

“…Considerable work has been done to formulate polymerantiviral drug nanoparticles with synthetic or semisynthetic polymers (Dembri et al 2001;Löbenberg et al 1998;Destache et al 2009;Mainardes et al 2009;Sharma and Garg 2010;Duan et al 2010). More recently, studies have shown that polysaccharides are very promising for oral drug delivery due to their affinity for complexing with a variety of drugs which can suppress drug crystallization, their relatively high glass transition temperatures and their biocompatibility (Sandra 2009).…”