Niosomal Hydrogel Containing Copaifera multijuga Oleoresin: Development, Characterization, and Preliminary In Vitro Cytocompatibility

Abstract Copaifera multijuga Hayne oleoresin is a natural product containing bioactive terpenoid compounds that has attracted interest for pharmaceutical and topical applications. However, its incorporation into topical formulations may be limited by its physicochemical characteristics and potential cellular effects. This study aimed to develop and characterize a niosomal hydrogel containing C. multijuga oleoresin, with particular emphasis on its physicochemical, structural, rheological, and cytotoxicity properties. Niosomes composed of Tween 80 and cholesterol were developed using a design of experiments and evaluated for mean vesicle size and polydispersity index over 60 days. The most promising formulation was further characterized for ζ-potential and encapsulation efficiency, and a niosomal hydrogel containing 100 mg of Tween 80, 10 mg of cholesterol, and 300 mg of oleoresin was prepared. The formulations were evaluated for spreadability, rheological behavior, nuclear magnetic resonance relaxometry, morphology, and cytotoxicity in human fibroblasts and keratinocytes. Niosome 1 was selected for incorporation into the hydrogel, which exhibited suitable organoleptic characteristics and a pH of 6.78. The niosomal hydrogel showed a spreadability factor of 16.57 ± 0.23 mm2/g and pseudoplastic non-Newtonian behavior. Nuclear magnetic resonance relaxometry indicated an increase in T2H relaxation time, suggesting greater molecular mobility compared with the blank hydrogel. Morphological analysis showed that the vesicles remained predominantly individualized after incorporation into the hydrogel, without evident structural disruption. Free oleoresin reduced cellular metabolic activity concentration-dependently. Niosomal encapsulation attenuated this effect, particularly in fibroblasts, while the hydrogel showed concentration-dependent effects on cellular metabolic activity. Overall, the findings demonstrate the feasibility of incorporating C. multijuga oleoresin into a niosomal hydrogel and provide physicochemical, structural, rheological, and cytotoxicity data supporting its potential as a topical delivery system.