?-cyclodextrin nanosponges as multifunctional ingredient in water-containing semisolid formulations for skin delivery

A ?-cyclodextrin nanosponge cross-linked with pyromellitic dianhydride (?NS-PYRO) is reported for the first time as multifunctional ingredient in semisolid formulations for drug delivery to the skin. The role of ?NS-PYRO on solubilization and stabilization of the photosensitizer benzoporphyrin-derivative monoacid ring A (BPDMA) and all-trans retinoic acid (atRA) as well as its effect on skin permeation of diclofenac (DIC) was investigated. Aqueous solutions, gels, and cream-gels were prepared from mixtures of ?NS-PYRO with a conventional gelling agent at specific ratios. The incorporation of BPDMA in ?NS-PYRO water solutions prevented its aggregation and gave kinetically stable complexes with high photostability and singlet oxygen generation upon irradiation. atRA incorporated in the ?NS-PYRO-containing gel demonstrated a remarkable stability as compared with the formulation without ?NS-PYRO, resulting in an eightfold increase of its lifetime. Skin permeation studies highlighted that ?NS-PYRO in gels and cream-gels containing DIC significantly decreased the amount of drug permeated through the skin while increasing its amount in stratum corneum and viable epidermis. Overall, swellable ?NS-PYRO turns to be a multifunctional coingredient with potential in topical monophasic and biphasic formulations to stabilize light-sensitive drugs and to localize the action of highly penetrating drugs in the external layers of skin.