[beta]-Cyclodextrin Nanosponges as Multifunctional Ingredient in Water-Containing Semisolid Formulations for Skin Delivery

A [beta]-cyclodextrin nanosponge cross-linked with pyromellitic dianhydride ([beta]NS-PYRO) is reported for the first time as multifunctional ingredient in semisolid formulations for drug delivery to the skin. The role of [beta]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 [beta]NS-PYRO with a conventional gelling agent at specific ratios. The incorporation of BPDMA in [beta]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 [beta]NS-PYRO-containing gel demonstrated a remarkable stability as compared with the formulation without [beta]NS-PYRO, resulting in an eightfold increase of its lifetime. Skin permeation studies highlighted that [beta]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 [beta]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. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3941-3949, 2014