Co-administration of African potato and cisplatin for treating breast and prostate cancers using a Pheroid® delivery system

Abstract

The cancer burden is increasing worldwide and is expected tobecome the most important barrier to increasing life expectancy 21stcentury. Low- and middle-income countries are expected to showthe biggest increase in incidence. Cisplatin is a frequently usedchemotherapy, however, challenges like drug resistance and sideeffects have yet to be overcome. A promising solution to thisproblem is the co- administration of cisplatin with other compounds.Many cancer patients in sub-Saharan countries co-administer herbaland prescription drugs. African potato (AP) is a popular choice for itsnegligible side effects and immune-boosting properties. One problemassociated with orally administered drug is poor bioavailability. ThePheroid® delivery system has shown to improve drug bioavailabilityand efficacy. No studies have been done on the interaction between AP and cisplatin, hence, this study aims to formulate a combinationof AP and cisplatin in Pheroids® and evaluate its anticancerproperties. Cytotoxicity of AP and cisplatin will be testedin vitroagainst breast (MCF-7) and prostate (PC-3) cancer cell lines todetermine the combination (CI) and dose reduction index of AP withcisplatin. Pheroids® will be examined for their optimal formulation.Anticancer activity of Pheroid® formulations will be tested throughvarious assays. For the pharmacokinetic study, Sprague- Dawley ratswill be used due to the volume of the blood samples required. Ratswill be administered with cisplatin, unformulated AP-cisplatin orPheroid® formulated AP-cisplatin (N= 10). For the efficacy study,nude mice that will be used as the models have already beenestablished. Animals will be implanted with either PC-3 or MCF-7cells. Once tumor volume has reached≥150 mm3 they will be treatedwith cisplatin, unformulated AP-cisplatin, Pheroid® formulated AP-cisplatin or empty Pheroids® (N= 10). AP and cisplatin have asimilar mode of action, hence synergistic activity whenco-administered is expected. As a result, lower concentrations ofcisplatin are expected to yield potent activity compared to individualadministration, for both Pheroid® formulations and free drugformulations