Multi-drug loaded polymeric micelles for simultaneous delivery of poorly soluble anticancer drugs.
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.
Shin
Ho-Chul
HC
Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, Madison, WI 53705, USA.
Alani
Adam W G
AW
Rao
Deepa A
DA
Rockich
Nicole C
NC
Kwon
Glen S
GS
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
D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; C000515:cremophor EL; D005990:Glycerol