Injectable lipid liquid crystalline based formulation of doxorubicin to fight against cancer

Aim and Background: Despite considerable advancements in developing efficient drug delivery strategies, cancer still remained one of the leading causes of death world- wide. The serious challenges are the low concentration of the cytotoxic agent at the tumor microenvironment and the systemic toxicity of the chemotherapeutics. With this in mind, we developed an injectable lipid liquid crystalline (LLC) based formulation of doxorubicin with sustained release pattern which provide sufficient dose of doxorubicin at the target tissue. Methods: 18 different formulations of LLC loaded with doxorubicin were synthesized using Box-Behnken method via different ratios of phosphatidyl choline: sorbitan monooleate, N-Methyl-2-pyrrolidone and tween 80. Afterwards, physicochemical characteristics of the formulations were studied. Then, in vivo tumor inhibitory effect of the selected formulations in C26 tumor bearing mouse model was investigated. Results and discussion: The results revealed that F1 (DOX loaded PC: SMO/NMP/Tween 80 (50:50/50/2 w/w%)) and F2 (DOX loaded PC: SMO/NMP (50:50/50 w/w%)) showed pseudoplastic behavior as well as being syringeable. Additionally, doxorubicin was released in a sustained manner for up to 60 days in both formulations. After intratumoral administration of the formulations, the results indicated a significant decrease in tumor size in both formulations compared to intravascular administration of doxorubicin. Prolonged release of the formulations was proved by animal imaging studies. Besides, histopathological studies demonstrated that the developed formulations showed no systemic toxicity. Conclusion: We believe that doxorubicin loaded lipid liquid crystalline formulations could efficiently eradicate cancers cells in C26 tumor bearing mouse models without systemic cytotoxicity.