DataVXACS Applied Materials & InterfacesPaper
journal article·2021-03-17Open access

Insulin Crystals Grown in Short-Peptide Supramolecular Hydrogels Show Enhanced Thermal Stability and Slower Release Profile

Rafael Contreras-Montoya, María Arredondo-Amador, Guillermo Escolano-Casado, Mari C. Mañas-Torres, Mercedes González, Mayte Conejero-Muriel, Vaibhav Bhatia, Juan J. Díaz-Mochón, Olga Martínez-Augustin, Fermín Sánchez de Medina, Modesto T. Lopez-Lopez, Francisco Conejero-Lara, José A. Gavira, Luis Álvarez de Cienfuegos

ACS Applied Materials & Interfaces· Volume 13· Issue 10
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Source abstract

Abstract

Protein therapeutics have a major role in medicine in that they are used to treat diverse pathologies. Their three-dimensional structures not only offer higher specificity and lower toxicity than small organic compounds but also make them less stable, limiting their in vivo half-life. Protein analogues obtained by recombinant DNA technology or by chemical modification and/or the use of drug delivery vehicles has been adopted to improve or modulate the in vivo pharmacological activity of proteins. Nevertheless, strategies to improve the shelf-life of protein pharmaceuticals have been less explored, which has challenged the preservation of their activity. Herein, we present a methodology that simultaneously increases the stability of proteins and modulates the release profile, and implement it with human insulin as a proof of concept. Two novel thermally stable insulin composite crystal formulations intended for the therapeutic treatment of diabetes are reported. These composite crystals have been obtained by crystallizing insulin in agarose and fluorenylmethoxycarbonyl-dialanine (Fmoc-AA) hydrogels. This process affords composite crystals, in which hydrogel fibers are occluded. The insulin in both crystalline formulations remains unaltered at 50 °C for 7 days. Differential scanning calorimetry, high-performance liquid chromatography, mass spectrometry, and in vivo studies have shown that insulin does not degrade after the heat treatment. The nature of the hydrogel modifies the physicochemical properties of the crystals. Crystals grown in Fmoc-AA hydrogel are more stable and have a slower dissolution rate than crystals grown in agarose. This methodology paves the way for the development of more stable protein pharmaceuticals overcoming some of the existing limitations.
Source: europepmc · Quality: candidate unverified · Source record ↗

Research context

PolymersCompositesMaterials processing

OpenAlex topics: Supramolecular Self-Assembly in Materials · RNA Interference and Gene Delivery · Lipid Membrane Structure and Behavior

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Departamento de Química Orgánica, Universidad de Granada, (UGR), C. U. Fuentenueva, Avda. Severo Ochoa s/n, E-18071 Granada, Spain

Instituto de Investigación Biosanitaria ibs.GRANADA, 18014 Granada, Spain

Departamento de Farmacología, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), School of Pharmacy, Instituto de Investigación Biosanitaria ibs.GRANADA, University of Granada, 18071 Granada, Spain

Laboratorio de Estudios Cristalográficos, Instituto Andaluz de Ciencias de la Tierra (Consejo Superior de Investigaciones Científicas-UGR), Avenida de las Palmeras 4, Armilla, 18100 Granada, Spain

Lamark Biotech Pvt. Ltd., VIT-TBI, 632 014 Vellore, Tamil Nadu, India

Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, UGR, 18011 Granada, Spain

Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Avenida de la Ilustración 114, 18016 Granada, Spain

Departamento de Bioquímica y Biología Molecular II, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), School of Pharmacy, Instituto de Investigación Biosanitaria ibs.GRANADA, University of Granada, 18071 Granada, Spain

Departamento de Física Aplicada, Facultad de Ciencias, UGR, C. U. Fuentenueva, Avda. Severo Ochoa s/n, E-18071 Granada, Spain

Departamento de Química Física, Facultad de Ciencias, UGR, C. U. Fuentenueva, Avda. Severo Ochoa s/n, E-18071 Granada, Spain

Funding

?la Caixa? Foundation · Ministry of Economy and Competitiveness of Spain · Junta de Andaluc?a-Consejer?a de Transformaci?n Econ?mica, Industria, Conocimiento y Universidades · EIT-Health

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