Objective: Low water solubility, high systemic toxicity and insignificant cellular uptake
have limited efficient clinical applications of the anti-tumor agent Paclitaxel (PTX). To overcome
these limitations, a Novel Nanostructured Lipid Carrier (NLC) modified with Folic Acid (FA) and
polyethylene glycol (PEG) was prepared by emulsion solvent evaporation method using cholesterol,
α-tocopherol, lecithin and Poloxamer. A partial factorial design was applied to determine the appropriate
levels of variables for optimized formulation. Formulations were evaluated for Particle Size
(PS), Zeta Potential (ZP), Entrapment Efficiency (EE), and release efficiency (RE72%). FA- and PEGconjugated
octadecylamine (FA-ODA and PEG-ODA) were synthesized and confirmed by FTIR and
H-NMR and incorporated either alone or in combination with the optimized formulation whose properties
were also evaluated. PTX-loaded optimized, targeted, pegylated, targeted/pegylated NLCs, pure
PTX, and Anzatax® along with their respective controls were selected for toxicity evaluation on human
breast cancer cell line, MCF-7, using MTT assay.
Methods: PS, ZP, EE%, and RE72% of the optimized formulation were 154.6 nm, -16.5 mv, 79.1%
and 49.3%, respectively. Incorporation of α-tocopherol as the liquid lipid allowed for more efficient
drug encapsulation, PS reduction, enhanced stability and sustained-release of the drug. Cytotoxicity of
PTX-loaded NLCs modified with both FA-ODA and PEG-ODA was significantly enhanced compared
to that of free PTX and other drug-loaded modified NLCs.
Results and Conclusion: The results suggest that preparation of NLCs with synthesized conjugates
might be a promising candidate for drug delivery of PTX to the cancerous cells and has a great potential
as a carrier for tumor targeting in breast cancer.