Preparation and characterization of polymeric micelles for solubilization of poorly soluble anticancer drugs.
The objective of this study is to investigate the solubilization of poorly water-soluble anticancer drugs, octaethylporphine (OEP), meso-tetraphenyl porphine (mTPP) and camptothecin (CPT), in Pluronic and polyethylene glycol-distearoylphosphatidylethanolamine (PEG-DSPE) polymeric micelles. Three different Pluronic and PEG-DSPE polymers with various chain lengths were chosen and micelle formulations were prepared by using various drug:polymer ratios. Formulations were characterized by critical micellization concentration (CMC) values of copolymers, micelle particle size and distribution, zeta potential, loading efficiency and stability. Polymers formed very stable, low CMC micelles with smaller sizes than 100 nm. It was shown that drug loading efficiency highly depends on the polymer type, drug type and their ratios. The most efficient drug loading was obtained by loading mTPP in PEG2000-DSPE and Pluronic F127 micelles. This result is attributed to phenyl groups in mTPP might lead to attraction between alkyl groups in the polymer and increase drug incorporation. PEG-DSPE formulations had higher zeta potential values indicating that they would be more stable against aggregation than Pluronic micelles. From the drug assay aspect Pluronic micelles remained more stable in 3-month long stability test. These results showed that besides their solubilizing effects, polymeric micelles could be useful as novel drug carriers for hydrophobic drugs.
Sezgin
Zerrin
Z
Department of Pharmaceutical Technology, School of Pharmacy, Ankara University, Tandogan, Ankara, Turkey. zsezgin@pharmacy.ankara.edu.tr
Yüksel
Nilufer
N
Baykara
Tamer
T
D000970:Antineoplastic Agents / Q000737:chemistry*; D002166:Camptothecin / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004355:Drug Stability; D057927:Hydrophobic and Hydrophilic Interactions; D008823:Micelles; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D020442:Poloxamer / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011166:Porphyrins / Q000737:chemistry; D012995:Solubility; D013329:Structure-Activity Relationship; D013997:Time Factors
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D010714:Phosphatidylethanolamines; D011108:Polymers; D011166:Porphyrins; C488938:octaethylporphyrin; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D020442:Poloxamer; D011092:Polyethylene Glycols; C049692:tetraphenylporphine; D002166:Camptothecin