Pub No:
Studies of a Benzoporphyrin Derivative With Pluronics
Hioka, N., Chowdhary, R.K., Chansarkar, N., Delmarre, D., Sternberg, E., and David Dolphin
Can. J. Chem.
80(10), 1321-1326
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 aggregation in many formulations, which results in inadequate drug delivery for clin. degeneration. The B-ring isomers, contrary to the A-ring isomers, exhibit high 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(I), a critical micelle concentration of P123 in water occurred at approximately 0.015 to 0.03%. The apparent pKa of compound I 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 I contains several molecules, and is formed by a catalyzed self-assembly process. Samples with 1 mg mL-1 of 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.

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