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.

[1]  V. Torchilin,et al.  Structure and design of polymeric surfactant-based drug delivery systems. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[2]  T. Okano,et al.  Polymer Design and Incorporation Methods for Polymeric Micelle Carrier System Containing Water-insoluble Anti-cancer Agent Camptothecin , 2004, Journal of drug targeting.

[3]  Y. M. Lee,et al.  Methoxy poly(ethylene glycol)/epsilon-caprolactone amphiphilic block copolymeric micelle containing indomethacin. I. Preparation and characterization. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[4]  T. Okano,et al.  Polymeric micelles for drug delivery: solubilization and haemolytic activity of amphotericin B. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[5]  Yokoyama Masayuki,et al.  Block copolymer micelles as vehicles for drug delivery , 1993 .

[6]  P. Ježek,et al.  Experimental photodynamic therapy with MESO‐tetrakisphenylporphyrin (TPP) in liposomes leads to disintegration of human amelanotic melanoma implanted to nude mice , 2003, International journal of cancer.

[7]  Y. M. Lee,et al.  Clonazepam release from core-shell type nanoparticles in vitro. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[8]  V. Torchilin,et al.  Diacyllipid-Polymer Micelles as Nanocarriers for Poorly Soluble Anticancer Drugs , 2002 .

[9]  Christine Allen,et al.  Nano-engineering block copolymer aggregates for drug delivery , 1999 .

[10]  M. Jones,et al.  Polymeric micelles - a new generation of colloidal drug carriers. , 1999, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[11]  J. Leroux,et al.  Solubilization of cyclosporin A in dextran-g-polyethyleneglycolalkyl ether polymeric micelles. , 2003, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[12]  Vladimir P. Torchilin,et al.  Polyethylene Glycol-Diacyllipid Micelles Demonstrate Increased Accumulation in Subcutaneous Tumors in Mice , 2002, Pharmaceutical Research.

[13]  Alexander V Kabanov,et al.  Pluronic block copolymers in drug delivery: from micellar nanocontainers to biological response modifiers. , 2002, Critical reviews in therapeutic drug carrier systems.

[14]  K. Kataoka,et al.  Block copolymer micelles for drug delivery: design, characterization and biological significance. , 2001, Advanced drug delivery reviews.

[15]  Vladimir P Torchilin,et al.  PEG-based micelles as carriers of contrast agents for different imaging modalities. , 2002, Advanced drug delivery reviews.

[16]  T. Okano,et al.  Incorporation of water-insoluble anticancer drug into polymeric micelles and control of their particle size. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[17]  Alexander V. Kabanov,et al.  A new class of drug carriers: micelles of poly(oxyethylene)-poly(oxypropylene) block copolymers as microcontainers for drug targeting from blood in brain☆ , 1992 .

[18]  J. Blais,et al.  Photodynamic efficiency of diethylene glycol-linked glycoconjugated porphyrins in human retinoblastoma cells. , 2006, Journal of medicinal chemistry.

[19]  Can Zhang,et al.  Self-assembly and characterization of paclitaxel-loaded N-octyl-O-sulfate chitosan micellar system. , 2004, Colloids and surfaces. B, Biointerfaces.

[20]  Alexander V. Kabanov,et al.  Relationship between pluronic block copolymer structure, critical micellization concentration and partitioning coefficients of low molecular mass solutes , 2000 .

[21]  J. Dey,et al.  Characterization of micelle formation of dodecyldimethyl-N-2-phenoxyethylammonium bromide in aqueous solution. , 2006, Journal of colloid and interface science.

[22]  A. MacRobert,et al.  Photodynamic therapy: regulation of porphyrin synthesis and hydrolysis from ALA esters. , 2006, Journal of photochemistry and photobiology. B, Biology.

[23]  A B Houtsmuller,et al.  5-Aminolaevulinic acid-induced protoporphyrin IX accumulation in tissues: pharmacokinetics after oral or intravenous administration. , 1998, Journal of photochemistry and photobiology. B, Biology.

[24]  Chong-Su Cho,et al.  METHOXY POLY(ETHYLENE GLYCOL) AND CAPROLACTONE AMPHIPHILIC BLOCK CO POLYMERIC MICELLE CONTAINING INDOMETHACIN. II: MICELLE FORMATION AND DRUG RELEASE BEHAVIORS , 1998 .

[25]  Tom Obremski,et al.  Statistics for management , 1979 .

[26]  I. Kwon,et al.  Polymeric micelles of poly(2-ethyl-2-oxazoline)-block-poly(ε-caprolactone) copolymer as a carrier for paclitaxel , 2003 .

[27]  Vladimir P. Torchilin,et al.  Use of polyoxyethylene-lipid conjugates as long-circulating carriers for delivery of therapeutic and diagnostic agents , 1995 .