Wound-healing is a very complex and evolutionary process that involves a great variety of dynamic steps. Although different pharmaceutical agents have been developed to hasten the woundhealing process, the existing agents are still far from optimal. The present work aimed to prepare and evaluate the wound-healing efficacy of phenytoin-loaded copper nanoparticles (PHT-loaded CuNPs). CuNPs were biosynthesized using licorice aqueous extract. The prepared CuNPs were loaded with PHT by adsorption, characterized, and evaluated for wound-healing efficiency. Results showed that both plain and PHT-loaded CuNPs were monodisperse and exhibited a cubic and hexagonal morphology. The mechanism by which PHT was adsorbed on the surface of CuNPs was best fit by the Langmuir model with a maximum loaded monolayer capacity of 181 mg/g. The kinetic study revealed that the adsorption reaction followed the pseudo-second order while the thermodynamic parameters indicated that the adsorption process was physical in nature and endothermic, and occurred spontaneously. Moreover, the in vivo wound-healing activity of PHT-loaded CuNP impregnated hydroxypropylmethyl cellulose (HPMC) gel was carried out using an excisional wound model in rats. Data showed that PHT-loaded CuNPs accelerated epidermal regeneration and stimulated granulation and tissue formation in treated rats compared to controls. Additionally, quantitative real-time polymerase chain reaction (RT-PCR) analysis showed that lesions treated with PHT-loaded CuNPs were associated with a marked increase in the expression of dermal procollagen type I and a decrease in the expression of the inflammatory JAK3 compared to control samples. In conclusion, PHT-loaded CuNPs are a promising platform for effective and rapid wound-healing.

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Plant-derived proteins have emerged as leading candidates in several drug and food delivery applications in diverse pharmaceutical designs. Zein is considered one of the primary plant proteins obtained from maize, and is well known for its biocompatibility and safety in biomedical fields. The ability of zein to carry various pharmaceutically active substances (PAS) position it as a valuable contender for several in vitro and in vivo applications. The unique structure and possibility of surface covering with distinct coating shells or even surface chemical modifications have enabled zein utilization in active targeted and site-specific drug delivery. This work summarizes up-to-date studies on zein formulation technology based on its structural features. Additionally, the multiple applications of zein, including drug delivery, cellular imaging, and tissue engineering, are discussed with a focus on zein-based active targeted delivery systems and antigenic response to its potential in vivo applicability.