Studies of a Benzoporphyrin Derivative With Pluronics
Hioka, N., Chowdhary, R.K., Chansarkar, N., Delmarre, D., Sternberg, E., and David Dolphin
Can. J. Chem.
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.