Cited by 4,792Nanoparticle-Based Drug DeliveryUltrasound and Hyperthermia ApplicationsRNA Interference and Gene Delivery

Doxil® — The first FDA-approved nano-drug: Lessons learned

Barenholz, Yechezkel (Chezy)·2012·Journal of Controlled Release

Abstract

Doxil®, the first FDA-approved nano-drug (1995), is based on three unrelated principles: (i) prolonged drug circulation time and avoidance of the RES due to the use of PEGylated nano-liposomes; (ii) high and stable remote loading of doxorubicin driven by a transmembrane ammonium sulfate gradient, which also allows for drug release at the tumor; and (iii) having the liposome lipid bilayer in a "liquid ordered" phase composed of the high-T(m) (53 °C) phosphatidylcholine, and cholesterol. Due to the EPR effect, Doxil is "passively targeted" to tumors and its doxorubicin is released and becomes available to tumor cells by as yet unknown means. This review summarizes historical and scientific perspectives of Doxil development and lessons learned from its development and 20 years of its use. It demonstrates the obligatory need for applying an understanding of the cross talk between physicochemical, nano-technological, and biological principles. However, in spite of the large reward, ~2 years after Doxil-related patents expired, there is still no FDA-approved generic "Doxil" available.

Integrity signals

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Crossref · 10.1016/j.jconrel.2012.03.020

Cites

127 of 127 references verified0 citation errors · 0 not checkable

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  • PEG coating on liposomes is a successful attempt to avoid RES recognition of the nanocarrier system.

    “Among such attempts, polyethylene glycol (PEG) coating on liposomes is a successful attempt to avoid RES recognition of nanocarrier system (Barenholz, 2012; Wong et al., 2012).”

    From Nanotechnology: A Promising Approach for Delivery of Neuroprotective Drugs (2020) · cites this paper as Barenholz, 2012

  • The successful listing of pegylated liposome Doxil in 1995 proved feasibility of PEG coating technology.

    “The successful listing of pegylated liposome Doxil, the first nanoparticle therapeutic drug, in 1995 proved the feasibility of this technology.292”

    From Smart nanoparticles for cancer therapy (2023) · cites this paper as [292]

  • Doxil, a PEG functionalized liposomal doxorubicin, was the first nanomedicine approved for anticancer medications (FDA in 1995).

    “Doxil, a PEG functionalized liposomal doxorubicin, was the first nanomedicine that has been approved for anticancer medications (FDA in 1995).292”

    From Smart nanoparticles for cancer therapy (2023) · cites this paper as [292]

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Authors
Barenholz, Y. (.
Affiliations
Hebrew University of Jerusalem (IL)
Corresponding author
Barenholz, Yechezkel (Chezy)
Venue
Journal of Controlled Release
Publisher
Elsevier BV
Published
2012-06
Volume
160
Issue
2
Pages
117-134
ISSN
0168-3659 (ISSN-L)
OpenAlex
W1989230986
Cited by
4,792
References
140
Citations by year
2026: 415 · 2025: 541 · 2024: 462 · 2023: 405 · 2022: 444 · 2021: 441 · 2020: 436 · 2019: 303 · 2018: 324 · 2017: 284 · 2016: 243 · 2015: 188 · 2014: 174 · 2013: 106 · 2012: 23
FWCI
8.16
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Controlled Release (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords
pegylated liposomal doxorubicin, PEGylated liposomes, nanotherapeutics, doxorubicin, enhanced permeability and retention effect, passive tumor targeting, liposome circulation time, remote loading, phosphatidylcholine, cholesterol, drug release, generic drug availability
MeSH terms
Antibiotics, Antineoplastic, Chemistry, Pharmaceutical, Delayed-Action Preparations, Doxorubicin, Drug Carriers, Drug Compounding, Humans, Liposomes, Solubility, United States, United States Food and Drug Administration, Drug Design, Drug Approval, Nanoparticles

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