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Critical Reviews™ in Therapeutic Drug Carrier Systems
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ISSN Imprimir: 0743-4863
ISSN En Línea: 2162-660X

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Critical Reviews™ in Therapeutic Drug Carrier Systems

DOI: 10.1615/CritRevTherDrugCarrierSyst.v20.i5.20
47 pages

Polymeric Micelles for Delivery of Poorly Water-Soluble Compounds

Glen S. Kwon
School of Pharmacy, University of Wisconsin, Madison, Wisconsin, USA

SINOPSIS

Amphiphilic polymers assemble into nanoscopic supramolecular core-shell structures, termed polymeric micelles, which are under extensive study for drug delivery. There are several reasons for this growing interest. Polymeric micelles may be safe for parenteral administration relative to existing solubilizing agents (for instance, Cremophor EL), permitting an increase in the dose of potent yet toxic and poorly water soluble compounds. Polymeric micelles solubilize important poorly water-soluble compounds, such as amphotericin B (AmB), propofol, paclitaxel, and photosensitizers. A major factor in drug solubilization is the compatibility of a drug and a core of a polymeric micelle. In this context, we may consider Pluronics®, poly(ethylene glycol) (PEG)-phospholipid conjugates, PEG-b-poly(ester)s, and PEG-b-poly(L-amino acid)s for drug delivery. Polymeric micelles may circulate for prolonged periods in blood, evade host defenses, and gradually release drug. Thus, they may show a preferential accumulation at sites of disease such as solid tumors. Polymeric micelles inhibit p-glycoprotein at drug-resistant tumors, gastrointestinal tract, and blood/brain barrier, perhaps providing a way to overcome drug resistance in cancer and increase drug absorption from the gut and drug absorption into the brain. Lastly, polymeric micelles may reduce the self-aggregation of polyene antibiotics, key membrane-acting drugs used to combat lifethreatening systemic fungal diseases. In this way, they may reduce its dose-limiting toxicity without a loss of antifungal activity.


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