Solubilization of the novel anionic amphiphilic photosensitizer TPCS 2a by nonionic Pluronic block copolymers

• Published in: European journal of pharmaceutical sciences 2011-06, Vol.43 (3), p.180-187
• Main Authors: Lilletvedt, M., Smistad, G., Tønnesen, H.H., Høgset, A., Kristensen, S.
• Format: Article
• Language: English
• Subjects: Antibiotics, Antineoplastic - chemistry; Cancer; Chemistry, Pharmaceutical - methods; Chlorin; Excipients - chemistry; Formulation; Humans; Micelles; Microscopy, Atomic Force; Particle Size; Photochemical internalization; Photosensitizer; Photosensitizing Agents - chemistry; Pluronic; Poloxamer - chemistry; Porphyrins - chemistry; Solubility; Spectrophotometry, Ultraviolet; Surface-Active Agents - chemistry; Temperature; Viscosity
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2011.04.004

The influence of four nonionic Pluronic block copolymers (L44, F68, P123 and F127) on the solubilization and aggregation of the novel anionic amphiphilic photosensitizer TPCS 2a, intended for use in the technology of photochemical internalization (PCI), was evaluated in aqueous media as part of pharmaceutical preformulation studies. The evaluation was performed by use of UV–Vis spectroscopy for diluted samples of TPCS 2a (3 × 10 −6 M), and capillary viscosimetry, freezing point depression measurements and atomic force microscopy (AFM) at pharmaceutical relevant concentrations (2; 10 or 30 mg/ml TPCS 2a). The critical micelle concentration (CMC) of the Pluronics in presence of TPCS 2a was determined spectrophotometrically. The Pluronic block copolymers solubilized the photosensitizer above CMC at ambient temperature by formation of vehicle–drug complexes apparently organized in networks of varying viscosity and morphology, which were sensitive towards the addition of neutral and charged excipients.