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Poly(vinyl alcohol) (PVA) can be physically cross-linked by repeated freeze-thaw (F-T) cycles, resulting in a cryogel. Despite the growing prevalence of the cryogelation process in the scientific literature, its multivariable nature, particularly the individual and synergistic impact of process variables on material properties, remains under-explored. The present work is the first systematic analysis quantifying the effect sizes associated with the influence of the key process parameters polymer concentration, number of cycles and thawing rates within F-T-cycles on the material properties of PVA cryogels as a drug delivery system for dermal applications. The variables analysed showed both positive and negative correlations with Young's modulus, gel strength and calculated mesh sizes of the polymer network to varying degrees. Moreover, it uniquely demonstrates the synergistic combination effects between individual process parameters, revealing mutual influences, that had not been characterized systematically before. The excellent suitability as a dermal drug delivery system was also demonstrated by both comparative drug release and drug permeation through the skin using diclofenac sodium as a model drug. Overall, this study provides the first systematic understanding of the impact of cryogelation process parameters on material properties and introduces a new and simple approach to individual selection of specific cryogelation conditions.
Wiedemann et al. (Tue,) studied this question.