Multi-drug loaded polymeric micelles for simultaneous delivery of poorly soluble anticancer drugs
Open accessAbstract
Current clinical and preclinical anticancer formulations are limited by their use of toxic excipients and stability issues upon combining different drug formulations. We have found that poly(ethylene glycol)-block-poly(d,l lactic acid) (PEG-b-PLA) micelles can deliver multiple poorly water-soluble drugs at clinically relevant doses. Paclitaxel (PTX), etoposide (ETO), docetaxel (DCTX) and 17-allylamino-17-demethyoxygeldanamycin (17-AAG) were solubilized individually in PEG-b-PLA micelles. Combinations of PTX/17-AAG, ETO/17-AAG, DCTX/17-AAG and PTX/ETO/17-AAG were also solubilized in PEG-b-PLA micelles. PEG-b-PLA micelles were characterized in terms of drug loading, size, stability and drug release. All anticancer agents in all combinations were all solubilized at the level of mg/mL and were stable for 24 h in the 2- and 3-drug combination PEG-b-PLA micelles. The stability of the 2- and 3-drug combination PEG-b-PLA micelles was due to the presence of 17-AAG. In vitro, t(1/2) values for 2- and 3-drug combination PEG-b-PLA micelles spanned 1-5 h. PEG-b-PLA micelles offer a promising alternative for combination drug therapy without formulation related side effects.
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PEG-b-PDLLA micelles containing two- or three-drug combinations such as paclitaxel/17-AAG, etoposide/17-AAG, docetaxel/17-AAG, and paclitaxel/etoposide/17-AAG had sizes around 30-40 nm and increased drug solubility up to 3-4 mg/mL in aqueous media.
“Polymeric micelles of 2- and 3-drug combinations such as paclitaxel/17-AAG, etoposide/17-AAG, docetaxel/17-AAG and paclitaxel/etoposide/17-AAG were small (~30–40 nm) and displayed enhanced drug solubility up to 3–4 mg/mL in aqueous media [260].”
From Polymeric micelles for the delivery of poorly soluble drugs: From nanoformulation to clinical approval. (2020) · cites this paper as [260]
Paclitaxel, etoposide, docetaxel, and 17-AAG were solubilized in PEG-b-PDLLA block copolymers as either single drugs or drug combinations.
“In 2009, they reported that paclitaxel, etoposide, docetaxel, and 17-AAG were solubilized in PEG-b-PDLLA block copolymers as either single drug or combination therapy.”
From Polymeric micelles for the delivery of poorly soluble drugs: From nanoformulation to clinical approval. (2020) · cites this paper as [260]
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- Authors
- Shin, H.-C., Alani, A. W. G., Rao, D. A., Rockich, N. C., & Kwon, G. S.
- Affiliations
- University of Wisconsin–Madison (US)
- Drake University (US)
- Corresponding author
- Kwon, Glen S.
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2009-12
- Volume
- 140
- Issue
- 3
- Pages
- 294-300
- ISSN
- 0168-3659 (ISSN-L)
- PMC
- PMC2787857
- OpenAlex
- W2006371280
- Cited by
- 243
- References
- 40
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 9 · 2023: 5 · 2022: 12 · 2021: 7 · 2020: 15 · 2019: 12 · 2018: 19 · 2017: 16 · 2016: 15 · 2015: 22 · 2014: 23 · 2013: 27 · 2012: 24
- FWCI
- 7.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI043346)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Keywords
- polymeric micelles, PEG-b-PLA, poorly water-soluble drugs, combination drug delivery, paclitaxel, etoposide, docetaxel, 17-AAG, drug solubilization, micelle stability, drug release kinetics, anticancer drug formulation, combination chemotherapy
- MeSH terms
- Animals, Antineoplastic Combined Chemotherapy Protocols, Chemistry, Pharmaceutical, Chromatography, High Pressure Liquid, Drug Carriers, Glycerol, Half-Life, Light, Micelles, Nephelometry and Turbidimetry, Magnetic Resonance Spectroscopy, Polymers, Scattering, Radiation, Solubility, Drug Design, Drug Delivery Systems, Rats
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