Barriers to drug delivery in solid tumors

Sriraman, Shravan Kumar; Aryasomayajula, Bhawani; Torchilin, Vladimir P

doi:10.4161/tisb.29528

Cited by 340Nanoparticle-Based Drug DeliveryDrug Transport and Resistance MechanismsAdvanced Drug Delivery Systems

Barriers to drug delivery in solid tumors

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Sriraman, Shravan Kumar, Aryasomayajula, Bhawani, Torchilin, Vladimir P·2014·Tissue Barriers

DOI 10.4161/tisb.29528PMC PMC4106925

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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.

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Multiple physiological barriers of the tumor microenvironment-dense extracellular matrix, cellular heterogeneity, hypoxic gradients, and elevated interstitial fluid pressure-hinder uniform distribution and accumulation of therapeutics, reducing treatment efficacy.
“Drug delivery to solid tumors is challenged by multiple physiological barriers arising from the tumor microenvironment, including dense extracellular matrix, cellular heterogeneity, hypoxic gradients, and elevated interstitial fluid pressure. These features hinder the uniform distribution and accumulation of therapeutics, reducing treatment efficacy.”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [1]
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The tumor microenvironment significantly influences drug penetration, retention, and therapeutic response.
“Together, these components create a tumor microenvironment (TME) that significantly influences drug penetration, retention, and therapeutic response [1,3,4].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [1]

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[135]Sawant RR Sriraman SK Navarro G Biswas S Dalvi RA Torchilin VP Polyethyleneimine-lipid conjugate-based pH-sensitive micellar carrier for gene delivery Biomaterials 2012 33 3942 51 10.1016/j.biomaterials.2011.11.088 22365809 PMC3527089 · DOI

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Barriers for Tumor Drug Delivery
Huang, Q., & Du, J. (2020) · Springer eBooks · doi:10.1007/978-981-15-5159-8_2

Authors: Sriraman, S. K., Aryasomayajula, B., & Torchilin, V. P.
Affiliations: Northeastern University (US)
Corresponding author: Torchilin, Vladimir P
ORCID: Sriraman, Shravan Kumar
Torchilin, Vladimir P
Venue: Tissue Barriers
Publisher: Informa UK Limited
Published: 2014-07
Volume: 2
Issue: 3
Pages: e29528
ISSN: 2168-8362 (ISSN-L)
2168-8370
DOI: 10.4161/tisb.29528
PMC: PMC4106925
OpenAlex: W2016834188
Cited by: 338
References: 154
Citations by year: 2026: 20 · 2025: 34 · 2024: 30 · 2023: 30 · 2022: 35 · 2021: 33 · 2020: 34 · 2019: 27 · 2018: 24 · 2017: 21 · 2016: 17 · 2015: 19 · 2014: 1
FWCI: 1.32
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc
Locations: Tissue Barriers (publishedVersion, cc-by-nc)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
Topics: Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
Keywords: drug delivery barriers, solid tumors, engineered nanoparticles, nanocarriers, tumor targeting, tumor microenvironment, pharmacokinetics, drug solubility, local drug delivery, multifunctional nanocarriers, dosing regimen, tumor resistance

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Barriers to drug delivery in solid tumors

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