title: Multi-drug loaded polymeric micelles for simultaneous delivery of poorly soluble anticancer drugs.
abstract: 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.
authors.affiliation: Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, Madison, WI 53705, USA.
authors.forename: Ho-Chul
authors.initials: HC
authors.lastname: Shin
authors.forename: Adam W G
authors.initials: AW
authors.lastname: Alani
authors.forename: Deepa A
authors.initials: DA
authors.lastname: Rao
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Rockich
authors.forename: Glen S
authors.initials: GS
authors.lastname: Kwon
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D016503:Drug Delivery Systems; D015195:Drug Design; D005990:Glycerol / Q000031:analogs & derivatives; D006207:Half-Life; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D009391:Nephelometry and Turbidimetry; D011108:Polymers; D051381:Rats; D012542:Scattering, Radiation; D012995:Solubility
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; C000515:cremophor EL; D005990:Glycerol