The Use of the QbD Approach to Optimize the Co-Loading of Simvastatin and Doxorubicin in Liposomes for a Synergistic Anticancer Effect

Abstract

The present study aimed to optimize a liposomal formulation co-encapsulating simvastatin (SIM) and doxorubicin (DOX) that has future perspectives in anticancer therapy. The optimization process was performed by implementing the Quality by Design concept and by considering the results of a previous screening study. Failure Mode and Effects Analysis was used for the identification of the potential critical factors, i.e., phospholipid, SIM and DOX concentration, which were assessed in an optimization experimental design with the purpose of designing an optimal formulation. The optimal formulation, meeting the established quality profile, was additionally characterized in terms of the release profile and antiproliferative effects. During dissolution studies, a novel chronoamperometric method was used for the simultaneous quantification of SIM and DOX. The obtained data confirmed the similarity of this method with a validated HPLC method. The anticancer potential of the optimal formulation was tested against two human cancerous cell lines, namely T47D-KBluc human mammary ductal carcinoma cell line and A549 human pulmonary cancer cell line. The results highlighted that the antiproliferative effect of the optimal formulation is concentration dependent and favors a synergistic effect of the two drugs.

Traditional Chinese Medicine Formulae QY305 Reducing Cutaneous Adverse Reaction and Diarrhea by its Nanostructure

“…However, a surprising phenomenon following the successful action of anticancer drugs arouses the scientific community's concern, namely, the adverse reactions observed in several patients. [ 1 , 2 ] To evaluate the efficacy of T‐QY305 on EGFRIs inducing cutaneous adverse reaction in cancer patients, we carried out clinical observation. Four cancer patients’ information was collected, who were treated with targeted therapy (mainly EGFRIs), occurring cutaneous adverse reaction after a few weeks, and then received T‐QY305 treatment.…”

“…[ 1 ] However, the previously cited therapeutic strategies are usually correlated with the development of resistance mechanisms and the occurrence of adverse reactions. [ 2 ] Here, we focus on adverse reactions induced by anticancer drugs. Among cancer‐targeted therapy, epidermal growth factor receptor inhibitors (EGFRIs) are widely used in clinical practice to treat cancer patients harboring activating mutations in EGFR, especially for non‐small cell lung cancer, breast cancer, colorectal carcinoma.…”

Multifunctional and stimuli-responsive liposomes in hepatocellular carcinoma diagnosis and therapy

“…Doxorubicin can be co-delivered with simvastatin in suppressing lung cancer progression [220] . Another type is thermosensitive magnetic liposomes for doxorubicin delivery [221] and adjusting protein corona component around liposomes improves their potential in doxorubicin delivery [222] .…”