Fabrication and in vivo evaluation of ligand appended paclitaxel and artemether loaded lipid nanoparticulate systems for the treatment of NSCLC: A nanoparticle assisted combination oncotherapy.

The aim of present study was to develop folate appended PEGylated solid lipid nanoparticles(SLNs) of paclitaxel(FPS) and artemether(FAS). The SLNs were prepared by employing high pressure homogenization technique. The results of MTT assays revealed better cytotoxicity of FPS when given in combination with FAS on human lung cancer cell line H-1299 as compared to pure drugs, unconjugated SLNs and FPS alone. The cellular uptake of FPS and FAS was confirmed by fluorescence imaging and flow cytometric analysis. In-vivo pharmacokinetic study revealed better absorption and long circulation of FPS and FAS, which further leads to increased relative bioavailability of drugs(13.81-folds and 7.07-folds for PTX and ART, respectively) as compared to their solutions counterpart. In-vivo pharmacodynamic study confirmed tumor regression of developed SLNs formulations, which was observed highest when used in combination of FPS and FAS. Serum creatinine, blood urea nitrogen(BUN), SGOT, albumin and total protein levels revealed that formulated FPS and FAS does not exhibit any renal and hepatic toxicity. It can be concluded that by administering ART-SLNs along with PTX-SLNs via oral route, anticancer potential of PTX was improved without any toxicity (both renal, hepatic), thus, indicating the potential of developed formulations in reducing dose related toxicity of PTX.