title: Preparation and Characterization of Lipophilic Doxorubicin Pro-drug Micelles.
abstract: Micelles have been successfully used for the delivery of anticancer drugs. Amphiphilic polymers form core-shell structured micelles in an aqueous environment through self-assembly. The hydrophobic core of micelles functions as a drug reservoir and encapsulates hydrophobic drugs. The hydrophilic shell prevents the aggregation of micelles and also prolongs their systemic circulation in vivo. In this protocol, we describe a method to synthesize a doxorubicin lipophilic pro-drug, doxorubicin-palmitic acid (DOX-PA), which will enhance drug loading into micelles. A pH-sensitive hydrazone linker was used to conjugate doxorubicin with the lipid, which facilitates the release of free doxorubicin inside cancer cells. Synthesized DOX-PA was purified with a silica gel column using dichloromethane/methanol as the eluent. Purified DOX-PA was analyzed with thin layer chromatography (TLC) and (1)H-Nuclear Magnetic Resonance Spectroscopy ((1)H-NMR). A film dispersion method was used to prepare DOX-PA loaded DSPE-PEG micelles. In addition, several methods for characterizing micelle formulations are described, including determination of DOX-PA concentration and encapsulation efficiency, measurement of particle size and distribution, and assessment of in vitro anticancer activities. This protocol provides useful information regarding the preparation and characterization of drug-loaded micelles and thus will facilitate the research and development of novel micelle-based cancer nanomedicines.
authors: School of Pharmacy, Hampton University; FENG.LI@hamptonu.edu.
authors: Feng
authors: F
authors: Li
authors: School of Pharmacy, Hampton University.
authors: Candace
authors: C
authors: Snow-Davis
authors: School of Pharmacy, Hampton University.
authors: Chengan
authors: C
authors: Du
authors: School of Pharmacy, Hampton University.
authors: Mikhail L
authors: ML
authors: Bondarev
authors: School of Pharmacy, Hampton University.
authors: Marilyn D
authors: MD
authors: Saulsbury
authors: School of Pharmacy, Hampton University.
authors: Simone O
authors: SO
authors: Heyliger
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D010316:Particle Size; D011108:Polymers; D011355:Prodrugs
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D011355:Prodrugs; D004317:Doxorubicin