Prospective insulin-based ophthalmic delivery systems for the treatment of dry eye syndrome and corneal injuries

Autor(es)

Cruz-Cazarim, Estael L. C. ^[1] ; Cazarim, Maurilio S. ^[1] ; Ogunjimi, Abayomi T. ^[1] ; Petrilli, Raquel ^[1] ; Rocha, Eduardo M. ^[2] ; Lopez, V, Renata F.

Afiliação do(s) autor(es)

^[1] V, Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Av Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Med Ribeirao Preto, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS; v. 140, p. 1-10, JUL 2019.
• Citações Web of Science: 0

Resumo

The presence of insulin (INS) receptors on the ocular surface (OS) and lacrimal gland (LG), and the high prevalence of dry eye syndrome (DES) and corneal lesions in diabetic patients suggest that INS is relevant for OS homeostasis and wound healing. The study aims at developing delivery systems for the topical administration of INS to the OS in order to improve INS local bioavailability and evaluate the influence of the delivery systems on DES in diabetic rats (DM) (n = 05/group). Chitosan microparticles (MP), chitosan/poloxamer gel (GEL) and MP-loaded GEL (GELMP), with or without INS were developed. Formulations were instilled into the eyes of diabetic rats (DM) for 15 days and the tear fluid volume, corneal cells morphology and cornea thickness were assessed and compared with an aqueous dispersion of INS (DISP-INS). All delivery systems had pH of about 6, osmolality suitable for topical application and positive zeta potential. The MPs with or without INS had sizes close to 4 mu m, spherical morphology and INS encapsulation efficiency of 77 +/- 6%. DISP-INS and GELMP-INS formulations produced tear secretion amounts significantly higher than those receiving formulations containing no INS and similar to healthy animals. Cornea surface impression cytology showed that treatment with INS-delivery systems and not DISP-INS almost normalized cells morphology. Treatment with GELMP-INS increased INS by 2.5 in the LG and eyeball as compared to the groups treated with GEL-INS and MP-INS, while treatment with DISP-INS left no traces of drug in the eye after treatment termination. GEL and GELMP containing INS were also able to normalize the thickness of the corneal epithelia. In conclusion, GELMP-INS normalized tear fluid volume, corneal thickness, protected corneal cells morphology and increased ocular bioavailability of INS, making it a promising treatment strategy for DES and corneal lesions. (AU)

• Processo FAPESP: 16/03584-1 - Desenvolvimento e validação de uma ferramenta farmacoeconômica para a implantação da atenção farmacêutica para pacientes hipertensos no sistema público de saúde do brasil
• Beneficiário: Maurilio de Souza Cazarim
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 14/22451-7 - Sistemas de liberação sustentada e direcionada de fármacos para o tecido epitelial
• Beneficiário: Renata Fonseca Vianna Lopez
• Modalidade de apoio: Auxílio à Pesquisa - Temático