Review article

Importance of integrating nanotechnology with pharmacology and physiology for innovative drug delivery and therapy – an illustration with firsthand examples

Authors: Rui Xue ZHANG1,2, Jason LI1, Tian ZHANG1, Mohammad A AMINI1, Chunsheng HE1, Brian LU1, Taksim AHMED1, HoYin LIP1, Andrew M RAUTH3, Xiao Yu WU1
1 Advanced Pharmaceutics & Drug Delivery Laboratory, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
2 School of Life Sciences, Northwestern Polytechnical University, Xi’an, China;
3 Departments of Medical Biophysics and Radiation Oncology, University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
Corresponding to: Xiao Yu WU: xywu@phm.utoronto.ca,
DOI: 10.1038/aps.2018.33
Received: 9 January 2018
Accepted: 19 February 2018
Advance online: 26 April 2018

Abstract

Abstract
Nanotechnology has been applied extensively in drug delivery to improve the therapeutic outcomes of various diseases. Tremendous efforts have been focused on the development of novel nanoparticles and delineation of the physicochemical properties of nanoparticles in relation to their biological fate and functions. However, in the design and evaluation of these nanotechnology-based drug delivery systems, the pharmacology of delivered drugs and the (patho-)physiology of the host have received less attention. In this review, we discuss important pharmacological mechanisms, physiological characteristics, and pathological factors that have been integrated into the design of nanotechnology-enabled drug delivery systems and therapies. Firsthand examples are presented to illustrate the principles and advantages of such integrative design strategies for cancer treatment by exploiting 1) intracellular synergistic interactions of drug-drug and drug-nanomaterial combinations to overcome multidrug-resistant cancer, 2) the blood flow direction of the circulatory system to maximize drug delivery to the tumor neovasculature and cells overexpressing integrin receptors for lung metastases, 3) endogenous lipoproteins to decorate nanocarriers and transport them across the blood-brain barrier for brain metastases, and 4) distinct pathological factors in the tumor microenvironment to develop pH- and oxidative stress-responsive hybrid manganese dioxide nanoparticles for enhanced radiotherapy. Regarding the application in diabetes management, a nanotechnologyenabled closed-loop insulin delivery system was devised to provide dynamic insulin release at a physiologically relevant time scale and glucose levels. These examples, together with other research results, suggest that utilization of the interplay of pharmacology, (patho-) physiology and nanotechnology is a facile approach to develop innovative drug delivery systems and therapies with high efficiency and translational potential.
Keywords: nanotechnology; pharmacology; physiology; pathophysiology; drug delivery systems; drug synergism; blood-brain barrier; tumor metastasis; diabetes mellitus; anticancer therapy