Lipid-derivatized poly(ethylene glycol) micellar formulations of benzoporphyrin derivatives
| Autor: | Theresa M. Allen, Janny X. Zhang, Anthony S. K. Vancouver Boey, Ron Boch, Christian B. Hansen |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Porphyrins
Chemistry Pharmaceutical Pharmaceutical Science Micelle Dosage form Polyethylene Glycols chemistry.chemical_compound Mice medicine Tumor Cells Cultured Organic chemistry Animals Humans Photosensitizer Solubility Micelles Chromatography Dose-Response Relationship Drug Porphyrin Verteporfin Xenograft Model Antitumor Assays chemistry Covalent bond Mice Inbred DBA Drug carrier medicine.drug |
| Zdroj: | Journal of controlled release : official journal of the Controlled Release Society. 86(2-3) |
| ISSN: | 0168-3659 |
| Popis: | In this paper, we describe the development of micellar formulations for increasing the solubility of lipophilic benzoporphyrins. Using a simple procedure that is readily adaptable for large-scale manufacturing, both A-ring (1) and B-ring isomers (2) of benzoporphyrins could be readily formulated, at concentrations up to 1-2 mg/ml, into small micelles (20 nm in diameter) of methoxypoly(ethylene glycol) (M(r) 2000) covalently attached to the lipid anchor distearoylphosphatidylethanolamine (mPEG-DSPE). The formulations spontaneously formed upon hydration of a thin film containing mPEG-lipid and photosensitizer and were stable upon storage at 4 degrees C for at least 1 month. Self-association of the B-ring benzoporphyrin isomer in micelles could be efficiently inhibited by either increasing the molar ratio of mPEG(2000)-DSPE to benzoporphyrin or by increasing the pH of the preparation to pH 8.5. The formulation could be freeze-dried and stored indefinitely in the lyophilized form, with restoration of the original properties upon reconstitution. In vivo, the A-ring benzoporphyrin, verteporfin, had higher levels of delivery and greater tumor control in mice than the B-ring derivative when formulated in mPEG(2000)-DSPE micelles and administered intravenously. mPEG(2000)-DSPE micellar formulations also showed tumor control when administered by a single intratumoral injection followed by light irradiation to the tumor within 45-60 min after drug administration. PEG-containing micellar formulations may be a promising delivery system for benzoporphyrin monoesters for clinical applications. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect