Targeting β Cells with Cathelicidin Nanomedicines Improves Insulin Function and Pancreas Regeneration in Type 1 Diabetic Rats.

Autor:	Cristelo C; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto 4200-135, Portugal.; Centro de Engenharia Biológica, Universidade do Minho, Campus de Gualtar, Braga 4710-057, Portugal.; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto 4050-313, Portugal., Nunes R; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto 4200-135, Portugal.; IUCS-CESPU, Instituto Universitário de Ciências da Saúde, Gandra 4585-116, Portugal., Pinto S; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto 4200-135, Portugal.; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto 4050-313, Portugal., Marques JM; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto 4200-135, Portugal.; Faculdade de Farmácia, Universidade do Porto, Porto 4099-002, Portugal., Gama FM; Centro de Engenharia Biológica, Universidade do Minho, Campus de Gualtar, Braga 4710-057, Portugal., Sarmento B; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto 4200-135, Portugal.; IUCS-CESPU, Instituto Universitário de Ciências da Saúde, Gandra 4585-116, Portugal.
Jazyk:	angličtina
Zdroj:	ACS pharmacology & translational science [ACS Pharmacol Transl Sci] 2023 Oct 03; Vol. 6 (10), pp. 1544-1560. Date of Electronic Publication: 2023 Oct 03 (Print Publication: 2023).
DOI:	10.1021/acsptsci.3c00218
Abstrakt:	Type 1 diabetes (T1D) is an incurable condition with an increasing incidence worldwide, in which the hallmark is the autoimmune destruction of pancreatic insulin-producing β cells. Cathelicidin-based peptides have been shown to improve β cell function and neogenesis and may thus be relevant while developing T1D therapeutics. In this work, a cathelicidin-derived peptide, LLKKK18, was loaded in poly(lactic- co -glycolic acid) (PLGA) nanoparticles (NPs), surface-functionalized with exenatide toward a GLP-1 receptor, aiming the β cell-targeted delivery of the peptide. The NPs present a mean size of around 100 nm and showed long-term stability, narrow size distribution, and negative ζ-potential (-10 mV). The LLKKK18 association efficiency and loading were 62 and 2.9%, respectively, presenting slow and sustained in vitro release under simulated physiologic fluids. Glucose-stimulated insulin release in the INS-1E cell line was observed in the presence of the peptide. In addition, NPs showed a strong association with β cells from isolated rat islets. After administration to diabetic rats, NPs induced a significant reduction of the hyperglycemic state, an improvement in the pancreatic insulin content, and glucose tolerance. Also remarkable, a considerable increase in the β cell mass in the pancreas was observed. Overall, this novel and versatile nanomedicine showed glucoregulatory ability and can pave the way for the development of a new generation of therapeutic approaches for T1D treatment. Competing Interests: The authors declare no competing financial interest. (© 2023 American Chemical Society.)
Databáze:	MEDLINE
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