Preparation and cellular uptake evaluation of PEGylated and L-Carnitine modified Cisplatin liposomes by macrophage and cancer cells

Abstract

Introduction: The surface properties of liposomes have an inevitable role in bio-molecular interactions and can be modified for higher drug delivery efficiency. Purpose: This study was aimed to synthesize cholesteryl acetyl carnitine (CAC), and surface modify the cisplatin (CisP)-loaded liposomes with the intention of enhanced cancer cell uptake and investigation of macrophage cell uptake pattern. Methods: CAC was synthesized in amine free conditions and then characterized. In the following, blank and CisP-loaded liposomes modified/un-modified with CAC and polyethylene Glycol (PEG) were prepared by reverse micelle method and then evaluated for size, size distribution, morphology, drug loading, in vitro drug release, FTIR, and DSC. CisP analysis was performed by HPLC using the complexation method. Cytotoxicity and cellular uptake of the liposomes were investigated in cancer cells of MCF7, HT29, A549, and macrophage cells of RAW264.7. Results: The results of ATR-FTIR and NMR demonstrated the successful formation of CAC. An efficient binding affinity to the active site of four carnitine transporters was observed. Liposomal formulations showed spherical morphology with a particle size of 99-138 nm, narrow size distribution, negative surface charge of -12.5 to -28.3, encapsulation efficiency range of 84-88.2%, without certain interactions between components. All blank liposomes had low cytotoxicity at commonly applied liposome concentrations. CAC-modified liposomes had the highest toxicity. CAC and CAC+PEG modified liposomes demonstrated higher cellular uptake in all studied cell lines. Higher cytotoxicity of CAC in A549 cells may be due to the involvement of OCTNs in these cells. Conclusion: Carnitine modification of CisP-liposomes can be considered an effective approach for increasing cellular uptake and cytotoxicity in studied cancer and macrophage cells.