Shape mediated splenotropic delivery of buparvaquone loaded solid lipid nanoparticles

Abstract

Buparvaquone (BPQ)-loaded asymmetric solid lipid nanoparticles (SLN) prepared by a modified nanoprecipitation method were evaluated for splenotropic drug delivery. BPQ SLN exhibited an average particle size of 650.28 ± 6.75 nm with polydispersity index ≤ 0.3, entrapment efficiency of 96.57 ± 0.190%, and drug loading of 24.63 ± 0.042%. Scanning electron microscopy (SEM) revealed elongated particles with flattened and rounded edges. Aspect ratio, an important determinant of asymmetricity of the BPQ SLN, measured as the ratio of average length (1143 ± 0.083 nm) to width (419 ± 0.031 nm) was found to be 2.727 ± 0.19. The hemolytic potential of 10.86 ± 0.04% and good serum stability suggested feasibility for intravenous administration. ^99mTc-labeled BPQ SLN revealed high radiolabeling efficiency (> 95%) and good stability. Intravenous administration in mice revealed > 75% accumulation in the reticuloendothelial system organs. The percent radioactivity per gram of organ was in the order spleen > kidney > lungs > liver > lymph nodes, with high splenic accumulation and significantly lower concentration in the liver. An astoundingly high spleen/liver ratio with a maximum of 11.94 ± 1.37 at 3 h, which confirmed high splenic uptake is attributed to Kupffer cell bypass. Other factors contributing to splenotropy are the rigidity and the low molecular weight of the lipid in the BPQ SLN which enabled translocation of the particles into the splenic pulp. Our study proposes asymmetric BPQ SLN as a promising splenotropic delivery system for improved efficacy in theileriosis, a spleen resident infection.

Keywords: Asymmetric shape; Buparvaquone; Gamma scintigraphy; Solid lipid nanoparticles; Splenic uptake; Splenotropy.