Preparation, characterization and evaluation of cellular internalization of docetaxel solid lipid nanoparticles, modified with stearyl choline

Abstract

Background: Solid lipidic nanoparticles (SLNs) are promising nano drug delivery systems due to their nontoxic nature. Aim: Preparation, characterization and evaluation of cellular uptake of docetoxel loaded modified with stearylcholine (SC) and oleoylcholine (OC) Methods: For the synthesis of SC, first, stearic acid reacted with oxalyl chloride then the produced stearylchloride reacted with 2-(dimethylamino) ethanol and methyl iodide. Finally SC was synthesized in the form of white powder. OC was synthesized by the same method using oleic acid instead of stearic acid in the form of a brown paste. CMC and T Krafft were measured by conductometry. Particle size, charge and morphology of solid lipid nanoparticles (SLNs) were evaluated by DLS and SEM. drug loading capacity (DLC %), entrapment efficiency (EE %) and drug release were analyzed by HPLC. Cellular uptake was studied by Flow cytometry and fluorescent microscopy and cytotoxicity was evaluated by MTT assay on HFFF-2, A549 and MCF7 cells. Results: FT-IR, HNMR, and CNMR results confirmed that SC and OC were synthesized. The CMC values of SC and OC at 25 °C are 5.94 µM and 411.1 µM respectively. T Krafft of SC and OC is 10 °C. HLB of both SC and OC was estimated at 8.35. The particle size and zeta potential of SC- and OC- DTX loaded SLNs are 76 nm, +12.9 mV and 126 nm, +29.9 mV respectively. Their EE % is 90.65 % and 77.98 % and their DLC % is 2.53 % and 2.06 % respectively. The release profile of DTX-loaded SLNs exhibited a slow release pattern. SLN-SC-DTX showed enhanced cell uptake into MCF7 cells while internalization of SC- and OC- SLNs are higher into A549 cells. Conclusion: In conclusion SC and OC were synthesized successfully. They exhibited low CMC and T Krafft. Thermal behavior represented these materials are polymorph. Synthetic surfactants showed no toxic effects on human normal HFFF-2 cells; nonetheless, their toxicity on A549 lung cancer cells was demonstrated. Synthetic materials also showed more toxic effects on cancer cells compared to DTX at high concentrations and could be considered as a cancer treatment agent. Cellular uptake of SLN-SC/OC was a charge and size dependent phenomenon. Incorporation of cationic surfactants into SLN could enhance the cellular uptake. The order of cellular uptake ability into A549 cells was SLN-OC-DTX > SLN-SC-DTX > SLN-DTX, which was SLN-SC-DTX > SLN-OC-DTX = SLN-DTX into MCF7 cells.