Biosynthesis, Characterization, and Wound-Healing Activity of Phenytoin-Loaded Copper Nanoparticles
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Research Article Biosynthesis, Characterization, and Wound-Healing Activity of Phenytoin-Loaded Copper Nanoparticles Mohammed S. Saddik,1 Fahd M. Alsharif,2,3,9 Mohamed A. El-Mokhtar,4 Mostafa F. Al-Hakkani,5 Mona M. El-Mahdy,6 Hatem S. Farghaly,7 and Heba A. Abou-Taleb8
Received 4 February 2020; accepted 29 April 2020 Abstract. 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. KEY WORDS: phenytoin; copper nanoparticles; biosynthesis; licorice aqueous extract; wound-healing activity. Electronic supplementary material The online version of this article (https://doi.org/10.1208/s12249-020-01700-5) contains supplementary material, which is available to authorized users. 1
Department of Pharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Sohag University, Sohag, Egypt. 2 Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt. 3 Pharmaceutical Sciences Department, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536, USA. 4 Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt. 5 Department of Chemistry, Faculty of Science, New Valley University, Al-Kharja, Egypt. 6 Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt. 7 Department of Biochemistry, Faculty of Pha
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