Biopolymeric Insulin Membranes for Antimicrobial, Antioxidant, and Wound Healing Applications
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Published:2024-07-30
Issue:8
Volume:16
Page:1012
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ISSN:1999-4923
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Container-title:Pharmaceutics
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language:en
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Short-container-title:Pharmaceutics
Author:
Aguilar-Vázquez Rocío1, Romero-Montero Alejandra1ORCID, Del Prado-Audelo María L.2, Cariño-Calvo Lizbeth3, González-Del Carmen Manuel4, Vizcaíno-Dorado Pablo Adrián5, Caballero-Florán Isaac Hiram2, Peña-Corona Sheila Iraís1ORCID, Chávez-Corona Juan Isaac16, Bernad-Bernad María Josefa1, Magaña Jonathan J.25, Cortés Hernán5ORCID, Leyva-Gómez Gerardo17ORCID
Affiliation:
1. Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico 2. Tecnologico de Monterrey, Escuela de Ingenieria y Ciencias, Campus Ciudad de Mexico, Ciudad de Mexico 14380, Mexico 3. Facultad de Ciencias Químicas, Universidad Veracruzana, Orizaba 94340, Mexico 4. Facultad de Medicina, Universidad Veracruzana, Ciudad Mendoza 94740, Mexico 5. Laboratorio de Medicina Genómica, Departamento de Genómica, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Ciudad de México 14389, Mexico 6. Laboratorio de Investigación y Posgrado en Tecnología Farmacéutica, Universidad Nacional Autónoma de México-FESC, Campus 1, Cuautitlán Izcalli 54714, Mexico 7. Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de México 04510, Mexico
Abstract
Delayed wound healing increases the wound’s vulnerability to possible infections, which may have lethal outcomes. The treatments available can be effective, but the urgency is not fully encompassed. The drug repositioning strategy proposes effective alternatives for enhancing medical therapies for chronic diseases. Likewise, applying wound dressings as biodegradable membranes is extremely attractive due to their ease of application, therapeutic effectiveness, and feasibility in industrial manufacturing. This article aims to demonstrate the pleiotropic effects during insulin repositioning in wound closure by employing a biopolymeric membrane-type formulation with insulin. We prepared biopolymeric membranes with sodium alginate cross-linked with calcium chloride, supported in a mixture of xanthan gum and guar gum, and plasticized with glycerol and sorbitol. Human insulin was combined with poloxamer 188 as a protein stabilizing agent. Our investigation encompassed physicochemical and mechanical characterization, antioxidant and biological activity through antibacterial tests, cell viability assessments, and scratch assays as an in vitro and in vivo wound model. We demonstrated that our biopolymeric insulin membranes exhibited adequate manipulation and suitable mechanical resistance, transparency, high swelling capability (1100%), and 30% antioxidant activity. Furthermore, they exhibited antibacterial activity (growth inhibition of S. aureus at 85% and P. aeruginosa at 75%, respectively), and insulin promoted wound closure in vitro with a 5.5-fold increase and 72% closure at 24 h. Also, insulin promoted in vivo wound closure with a 3.2-fold increase and 92% closure at 10 days compared with the groups without insulin, and this is the first report that demonstrates this therapeutic effect with two administrations of 0.7 IU. In conclusion, we developed a multifunctional insulin-loaded biopolymeric membrane in this study, with the main activity derived from insulin’s role in wound closure and antioxidant activity, augmented by the antimicrobial effect attributed to the polymer poloxamer 188. The synergistic combination of excipients enhances its usefulness and highlights our innovation as a promising material in wound healing materials.
Funder
Chemical Sciences (UNAM) and acknowledges CONAHCYT DGAPA-UNAM for PAPIIT PAPIME School of Chemistry, UNAM María de los Dolores Campos Echeverría and Carolina Flores-Avila, School of Chemistry, UNAM “Círculo A.D.N.” Company
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