Co-delivery strategies to overcome multidrug resistance in ovarian cancer

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Abstract

Cancer is one of the leading causes of death and equally strikes both genders. Among women, ovarian cancer is responsible for many deaths as it remains symptomless in the earlier stages and generally diagnosed in third stage. At this point it becomes difficult to carry out de-bulking surgery and treatment with different chemotherapeutic drugs has shown resistance, a phenomenon known as multidrug resistance (MDR). Different treatment choices are available for ovarian cancer; however, this article only focuses on various co-delivery strategies, where two different agents are encapsulated in a single carrier and act via different pathways to overcome cancer cell resistance. Ovarian cancer develops MDR via different pathways but majorly involving pump and the non-pump mechanisms in most cases. To overcome MDR it is imperative to strike malignant cells from various directions. Nanocarriers are known to strike the pump mechanism by avoiding the drug efflux pump located on cellular membrane. The efflux pump can also be blocked by blocking activity of ATP binding cassette (ABC) membrane transporters. To stop the non-pump mechanism one can use chemosensitizers, genes, apoptotic factor and others. Treatment of cancer cells could even more effective if the drug is combined with co-agents in a single carrier with targeting moiety. These co-agents along with nanocarriers, allow the drug to accumulate in high enough concentrations in ovarian cancer cells to kill them without affecting normal cells.

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