Viscosity reduction of isotonic solutions of the photosensitizer TPCS2a by cyclodextrin complexation

Meso-tetraphenyl chlorin disulphonate (TPCS_2a) is a photosensitizer (PS) particularly developed and patented for use in the technology of photochemical internalization (PCI) against cancer. TPCS_2a is known to aggregate in aqueous media even at low concentrations (≥0.1?µM) and to form a high-viscosity network at clinically relevant concentrations (mM). The aim of this work was to evaluate the effect of two hydroxypropylated cyclodextrin derivatives of beta and gamma type, respectively i.e. HPβCD and HPγCD, on the aggregation and solubilization of TPCS_2a in isotonic solutions. Samples containing micromolar concentrations of TPCS_2a were studied spectrophotometrically, while samples containing a clinical relevant concentration (10?mM?=?9?mg/ml) of TPCS_2a were evaluated by dynamic viscosity measurements. HPβCD was determined to be a more suitable solubilizer of TPCS_2a than HPγCD in aqueous media both in the absence and presence of salt. The complexation stoichiometry between TPCS_2a/HPβCD at micromolar to millimolar concentrations of TPCS_2a was determined to be 1:3 and 1:2 in the absence and presence of isotonic NaCl, respectively. The network of TPCS_2a (10?mM) was broken down in the presence of 3% w/v (=?20?mM) HPβCD, i.e. a 1:2 molar ratio between TPCS_2a and the cyclodextrin. Formation of the inclusion complex resulted in low viscosity samples both in water and in the presence of isotonic NaCl or phosphate buffered saline (PBS) at 25?°C and 37?°C.