Strategies to Enhance the Drug Distribution: A Comprehensive Review
A heterogeneous mixture of cells with varying amounts of nutrients and oxygen composes the microenvironment inside tumors. Oxygen content variations result in survival or compensatory processes within tumors that may benefit a phenotype that is more malignant or lethal. Rapidly proliferating cells are richly nourished and positioned near blood vessels preferentially. Chemotherapy may target and destroy cells adjacent to the vasculature, while cells residing farther away are often not exposed to sufficient quantities of medication and may survive and repopulate after treatment. In order to devise more effective therapies, the dynamics of the tumor microenvironment can be manipulated. In this report, we identify important features of the microenvironment of the tumor and address techniques that can enhance the delivery and action of drugs. Within an extracellular matrix (ECM) protected by an irregular vascular network, solid tumors comprise a heterogeneous mix of tumor cells and non-malignant cells. Tumor blood vessels are often further apart than normal tissues and differ in blood flow, resulting in inadequate nutrient distribution and impaired clearance of tumor metabolic breakdown products.