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Review
. 2014 Jul 22:2:e29528.
doi: 10.4161/tisb.29528. eCollection 2014.

Barriers to drug delivery in solid tumors

Shravan Kumar Sriraman  1 , Bhawani Aryasomayajula  1 , Vladimir P Torchilin  1
Affiliations
Review

Barriers to drug delivery in solid tumors

Shravan Kumar Sriraman et al. Tissue Barriers. .

Abstract

Over the last decade, significant progress has been made in the field of drug delivery. The advent of engineered nanoparticles has allowed us to circumvent the initial limitations to drug delivery such as pharmacokinetics and solubility. However, in spite of significant advances to tumor targeting, an effective treatment strategy for malignant tumors still remains elusive. Tumors possess distinct physiological features which allow them to resist traditional treatment approaches. This combined with the complexity of the biological system presents significant hurdles to the site-specific delivery of therapeutic drugs. One of the key features of engineered nanoparticles is that these can be tailored to execute specific functions. With this review, we hope to provide the reader with a clear understanding and knowledge of biological barriers and the methods to exploit these characteristics to design multifunctional nanocarriers, effect useful dosing regimens and subsequently improve therapeutic outcomes in the clinic.

Keywords: EPR; MPS; biological barriers; cancer; drug delivery; multifunctional nanoparticles; nanoparticle; tumors.

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Figures

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Figure 1. Hemodynamics of blood flow
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Figure 2. Extravasation of nanoparticles from systemic circulation into the tumor interstitium
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Figure 3. The various mechanisms of cellular internalization of nanoparticles via clathrin-mediated endocytosis, caveolin-mediated endocytosis, clathrin-caveolin independent endocytosis, phagocytosis and macropinocytosis and their subsequent intracellular trafficking
See this image and copyright information in PMC

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