Formulation of temperature-sensitive pegylated doxorubicin nanoliposomes and investigation of antitumor effects in C26 cell line

Aim and Background: Lyso-thermosensitive liposomal doxorubicin (LTLD, ThermoDox) is the first heat-activated formulation of a liposomal drug carrier to be utilized in human clinical trials. Lyso-thermosensitive liposomal doxorubicin (LTLD, ThermoDox) is the first heat-activated formulation of a liposomal drug carrier to be utilized in human clinical trials. The optimal molar ratio of 86.5:3.8:10(DPPC: DSPE-mPEG2000: MSPC) drives LTLD performance creating a drug-retaining bilayer that is critical to retaining its payload and then becomes unstable at temperatures 39.5 ⸰C. Unfortunately, ThermoDox formulation is instability in the bloodstream, and the drug is released in the bloodstream before reaching the tumor site. in this study, adding different percentages of hydrogenated Soy phosphatidylcholine (HSPC) components will increase the stability of the formulation in blood. In this way, this formulation will be able to accumulate in the tumor environment with the EPR mechanism and establish a more effective interaction with tumor cells. Methods: Different liposomal formulations were prepared using Solvent evaporation and remote loading methods and finally liposomal formulations were selected considering the total characteristics of lipid structure, size, zeta potential, homogeneity, retention percentage, and the final concentration of doxorubicin in 1 ml of the formulation. Preparing different liposomal formulations using DPPC/MSPC/DSPE-mPEG2000 phospholipids and adding HSPC phospholipids with different percentages and hydration with citrate buffers separately. Results and discussion: After preparing the formulations, the cytotoxicity test and their release (in three PH= 5.5, 6.5. 7.4), uptake, were performed on the C26 cell line at two temperatures of 37 ⸰C and 42⸰C. As a result of applying mild hyperthermia, the level of toxicity on C26 cell lines increased. Additionally, the formulation was more stable and had a lesser level of drug release at greater molar percentages of HSPC. The figure below shows the TEM electron microscope image of one of the prepared formulations. Conclusion: Our work improved a nano-sized Dox-LTSL formulation for stability and triggered drug delivery. Dox-LTSL had great drug loading efficiency, stability at physiological temperature in circulation, and quick drug release potential under local moderate hyperthermia