Folate conjugated Nano-Lipid construct of Paclitaxel for site-specific lung squamous carcinoma targeting

Abstract

The objective of this study was to evaluate the effectiveness of folate-conjugated nano-lipid constructs (F-NLCs) for targeting lung squamous carcinoma through both ex-vivo and in-vivo studies. Ligand-conjugated (F-NLCs) and non-conjugated (P-NLCs) formulations were prepared using the solvent evaporation method, with paclitaxel as the reference drug. The formulations were characterized for particle size, zeta potential, encapsulation efficiency, and drug loading capacity. The average particle size of P-NLCs and F-NLCs was found to be 190.1 ± 1.9 nm and 231.3 ± 2.3 nm, respectively. The percent entrapment efficiency of P-NLCs and F-NLCs was 85.14 ± 1.4 % and 82.42 ± 1.2 %, respectively. The drug loading for P-NLCs and F-NLCs was 25.3 ± 1.1 % and 24.2 ± 1.3 %, respectively. The haemolytic study revealed lower toxicity for F-NLCs (4.36 ± 0.6 %) compared to P-NLCs (12.36 ± 0.8 %) and paclitaxel (25.41 ± 0.4 %). Ex-vivo studies, employing the SRB method, demonstrated GI50 (µM) values of 9.72 for P-NLCs and 5.84 for F-NLCs, compared to 18.51 for the paclitaxel solution. Cellular uptake studies using Rhodamine-B dye-loaded NLCs (F-D-NLCs), observed through fluorescence microscopy, indicated higher accumulation in the lung sac compared to D-NLCs. In vivo research, focusing on biodistribution and pharmacokinetics, was conducted on Wistar rats to confirm the efficacy of F-NLCs. Biodistribution results showed concentrations of 25.86 ± 0.39 % for F-NLCs and 3.14 ± 0.46 % for the paclitaxel solution in lung squamous carcinoma cells, indicating a significant improvement in drug concentration within carcinogenic squamous cells with F-NLCs. The findings conclude that F-NLCs are a safe, stable, and promising drug delivery system for the targeted treatment of lung squamous carcinoma.