Overcoming transport barriers for interstitial-, lymphatic-, and lymph node-targeted drug delivery.
Despite drug formulation improving circulation times and targeting, efficacy is stymied by inadequate penetration into and retention within target tissues. This review highlights the barriers restricting delivery to the connective tissue interstitium, lymphatics, and lymph nodes as well as advances in engineering drug carriers to overcome these delivery challenges. Three-dimensional tissue physiology is discussed in the context of providing material design principles for delivery to these tissues; in particular the influence of interstitial and lymphatic flows as well as differential permeabilities of the blood and lymphatic capillaries. Key examples of materials with different characteristics developed to overcome these transport barriers are discussed as well as potential areas for further development.
George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, GA, 30332, USA ; Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, GA, 30332, USA.
Susan N
SN
Thomas
Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, GA, 30332, USA ; School of Materials Science and Engineering, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, GA, 30332, USA.
Alex
A
Schudel
drug delivery; interstitium; lymph node; lymphatics