Influence of Tumor Microenvironment on the Distribution and Elimination of Nano-formulations

Objective: To give an in-depth overview about the tumor and its surrounding microenvironment influencing distribution and elimination of nanoformulations. Mehtods: This up-to-date review will summarize the microenvironmental components and their influence on the various factors related to nanoformulations and tumor which affect the penetration, distribution, regulation and clearance of nanoformulations from the tumor cells. Results of recent advances in miroenvironmental tuning with nanoformulations will be evaluated mechanistically. In addition, those natures of tumors involving enhanced cancer therapy will be discussed. Finally, strategies of nanoparticulate design and decoration to achieve efficient drug delivery are presented. Results: Development of tumor is facilitated by its surrounding microenvironment and is regulated by different extra and intracellular components. Drug-loaded nanoformulations are mainly administered via oral and parenteral routes which reach tumor cells via different mechanisms. Chemotherapeutics get diffused from circulation into the surrounding microenvironment which latter get internalized into the cellular interstial area by passive diffusion mechanism due to virtue of size, charge, and pegylation effects, or by ligands and receptor mediated, or through enhanced permeability and retention effects through leaky apertures. Due to mildly acidic environment and hypoxic interstial environment, the influx of nanoformulations is hindered. The metabolites of the nanoformulations get diffused out from the tumor cells as a results of high interstial fluid pressure and get cleared either via liver or via renal execration. Conclusion: Well-understanding tumoral microenvironments which significantly affect distribution and elimination of nanoformulations is essential for engineering delivery systems with superior anti-tumoral effect.