Strategies for improving drug delivery: nanocarriers and microenvironmental priming

ABSTRACT

Introduction: The ultimate goal in the field of drug delivery is to exclusively direct therapeutic agents to pathological tissues in order to increase therapeutic efficacy and eliminate side effects. This goal is challenging due to multiple transport obstacles in the body. Strategies that improve drug transport exploit differences in the characteristics of normal and pathological tissues. Within the field of oncology, these concepts have laid the groundwork for a new discipline termed transport oncophysics.

Areas covered: Efforts to improve drug biodistribution have mainly focused on nanocarriers that enable preferential accumulation of drugs in diseased tissues. A less common approach to enhance drug transport involves priming strategies that modulate the biological environment in ways that favor localized drug delivery. This review discusses a variety of priming and nanoparticle design strategies that have been used for drug delivery.

Expert opinion: Combinations of priming agents and nanocarriers are likely to yield optimal drug distribution profiles. Although priming strategies have yet to be widely implemented, they represent promising solutions for overcoming biological transport barriers. In fact, such strategies are not restricted to priming the tumor microenvironment but can also be directed toward healthy tissue in order to reduce nanoparticle uptake.

KEYWORDS:

• Biodistribution
• biological barrier
• nanodelivery system
• priming agents
• transport ocophysics

Article highlights

• Localized drug delivery is an active area of research that aims to increase therapeutic efficacy and reduce side effects.

• Lesion-specific drug delivery is hampered by biological transport barriers.

• Solutions to improve drug delivery take advantage of differences between normal and pathological tissues.

• Localized drug delivery has been attempted with nanocarriers designed to overcome biological barriers.

• A less common strategy to improve drug delivery involves the use of priming agents that modulate the host environment in ways that favor lesion-specific drug accumulation.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This work was funded by the Houston Methodist Research Institute. Partial funds were acquired from: the Ernest Cockrell Jr. Distinguished Endowed Chair (M. Ferrari), the U.S. Department of Defense (W81XWH-09-1-0212, W81XWH-12-1-0414) (M Ferrari), the National Institutes of Health (U54CA143837, U54CA151668; M Ferrari), Nylands Nation Finland (J Wolfram), Victoriastiftelsen Finland (J Wolfram), and the Cancer Prevention Research Institute of Texas (RP121071) (M Ferrari and H Shen).