Silk fibroin films stabilizes and releases bioactive insulin for the treatment of corneal wounds

Insulin (INS) is a protein that plays a crucial role in many cellular functions, including wound healing processes. However, its topical ocular administration is a challenge, mainly because of INS degradation and low retention time, which can significantly reduce its bioavailability. The objective o...

Descripción completa

Detalles Bibliográficos
Autores: Cubayachi, Camila, Lemos, Camila Nunes, Pereira, Francieli, Dias, Karina, Herculano, Rondinelli Donizetti [UNESP], Freitas, Osvaldo de, Lopez, Renata F. V.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:Brasil
Institución:Universidade Estadual Paulista (UNESP)
Repositorio:Repositório Institucional da UNESP
Idioma:inglés
OAI Identifier:oai:repositorio.unesp.br:11449/186843
Acceso en línea:http://dx.doi.org/10.1016/j.eurpolymj.2019.06.022
http://hdl.handle.net/11449/186843
Access Level:acceso abierto
Palabra clave:Ocular delivery
Silk fibroin
Insulin
Drug delivery system
Film
Corneal wound
Descripción
Sumario:Insulin (INS) is a protein that plays a crucial role in many cellular functions, including wound healing processes. However, its topical ocular administration is a challenge, mainly because of INS degradation and low retention time, which can significantly reduce its bioavailability. The objective of this work was to develop films based on silk fibroin (SF), a natural polymer with anti-inflammatory properties, containing INS aimed at the sustained release of a bioactive INS in the eye for the treatment of corneal wounds. SF films containing 100 IU/cm(2) INS and glycerin as plasticizer were prepared by casting. They were homogeneous, transparent, permeable to water vapor, with low swelling index and high mechanical resistance. Fourier transformed infrared spectroscopy and differential scanning calorimetry analyses suggested the beta-sheet/Silk II conformation of SF and the occurrence of non-covalent interactions between INS and SF. Scanning electron microscopy suggested that the INS was embedded inside the film in its native globular form. In fact, the INS released from the film maintained its native conformation, as observed by circular dichroism, in addition to conserving its biological activity in vivo, reducing the blood glycemia of Wistar rats. Sustained release, of approximately 1 IU/cm(2)/h(1/2) of INS per hour, following a burst release, suggests that the film could be effective in the recovery of injured corneal epithelium, avoiding the need for the various daily administrations. Therefore, SF films demonstrated potential to transport and release INS in a sustained manner, a promising strategy for the treatment of corneal wounds.