Studies of a benzoporphyrin derivative with Pluronics
| Autor: | Ethan Sternberg, D Delmarre, David Dolphin, Noboru Hioka, R. K. Chowdhary, Namrata Chansarkar |
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| Rok vydání: | 2002 |
| Předmět: | |
| Zdroj: | Canadian Journal of Chemistry. 80:1321-1326 |
| ISSN: | 1480-3291 0008-4042 |
| Popis: | The synthetic route for the benzoporphyrin derivatives produces two regioisomers in equimolar quantities (ring A and B isomers). A derivative of the A-ring product, BPD-MA (benzoporphyrin-derivative monoacid ring A, verteporfin), has recently been approved in North America and Europe for the treatment of age-related macular degeneration. The B-ring isomers, contrary to the A-ring isomers, exhibit high aggregation in many formulations, which results in inadequate drug delivery for clinical uses. To avoid aggregation, a non-ionic surfactant polymer such as a Pluronic poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) may be used as a formulation excipient. The triblock polymer investigated here is designated P123 (or poloxamer 403). When used to formulate a monoacid benzoporphyrin B-ring derivative (2), a critical micelle concentration of P123 in water occurred at approximately 0.015 to 0.03%. The apparent pKaof compound 2 was dependent on its concentration in P123, and decreased as the molar ratio (P123:2) increased. High concentrations of P123 and neutral pH were found to be the best conditions to maintain the drug in its monomeric form. Kinetic studies suggest that the aggregate of 2 contains several molecules, and is formed by a catalyzed self-assembly process. Samples with 1 mg mL1of drug, at pH = 7.4, and 4.8% of Pluronic showed satisfactory capacity to load and keep monomers stable. This formulation has potential PDT applications.Key words: Pluronic, poloxamers, block copolymers, photosensitizing drug, photodynamic therapy (PDT), formulation, micelles. |
| Databáze: | OpenAIRE |
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