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Overcoming in vivo barriers to targeted nanodelivery
Author(s) -
Chrastina Adrian,
Massey Kerri A.,
Schnitzer Jan E.
Publication year - 2011
Publication title -
wiley interdisciplinary reviews: nanomedicine and nanobiotechnology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 72
eISSN - 1939-0041
pISSN - 1939-5116
DOI - 10.1002/wnan.143
Subject(s) - nanocarriers , drug delivery , transcytosis , in vivo , nanotechnology , nanoparticle , chemistry , pharmacology , medicine , materials science , endocytosis , biology , cell , biochemistry , microbiology and biotechnology
Nanoparticles have been investigated as promising nanocarriers for delivery of imaging and therapeutic agents for several decades, but have met with limited success. Although enormous progress in the fields of nanotechnology and nanoscience has been achieved, basic discoveries have not yet translated into effective targeted therapies. Nanoparticles can potentially improve the pharmacokinetics and pharmacodynamics of drugs; however, the complexity of in vivo systems imposes multiple barriers that severely inhibit efficiency and have to be overcome to fully exploit the theoretical potential of nanoparticles. Here, we address two major challenges to effective systemic nanodelivery. Both limited penetration across the vascular endothelium and uptake by the reticuloendothelial system (RES) substantially impede effectiveness of nanoparticle delivery into tissues. Although the design of nanoparticles with extended circulation half‐life is essential, it is not sufficient for effective penetration of nanoparticles across the formidable barrier formed by the vascular endothelium. Current nanodelivery systems rely on passive transvascular exchange and tissue accumulation. They require high dosages to create large concentration gradients that drive nanoparticles passively across the blood–tissue interface. However, passive accumulation has resulted in only a fractional dosage of nanoparticles penetrating into target tissue. This inevitably diminishes therapeutic efficacy and aggravates potential side effects. Although there are multiple ways to augment passive delivery, active delivery of targeted nanoparticles across the vascular endothelium could significantly increase the therapeutic index and decrease side effects of nanoparticle‐based drug delivery systems. Use of active transendothelial transport pathways, such as caveolae, may provide an effective solution to both target and deliver nanoparticles. WIREs Nanomed Nanobiotechnol 2011 3 421–437 DOI: 10.1002/wnan.143 This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > In Vivo Nanodiagnostics and Imaging