Investigation of therapeutic effects in the wound healing of chitosan/pGM-CSF complexes

Şalva, Emine; Alan, Saadet; Karakoyun, Berna; Çakalağaoğlu, Fulya; Özbaş, Suna; Akbuğa, Jülide

doi:10.1590/s2175-97902022e19668

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Brazilian Journal of Pharmaceutical Sciences

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Article • Braz. J. Pharm. Sci. 58 • 2022 • https://doi.org/10.1590/s2175-97902022e19668 copy

Investigation of therapeutic effects in the wound healing of chitosan/pGM-CSF complexes

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to promote the growth, proliferation, and migration of endothelial and keratinocyte cells. Chitosan has been widely used as a biopolymer in wound-healing studies. The aim of this study was to investigate the in vitro proliferative effects of chitosan/pGM-CSF complexes as well as the therapeutic role of the complexes in an in vivo rat wound model. The effect of complexes on cell proliferation and migration was examined. Wounds were made in Wistar-albino rats, and examined histopathologically. The cell proliferation and migration were increased weight ratio- and time-dependently in HaCaT and NIH-3T3 cell lines. Wound healing was significantly accelerated in rats treated with the complexes. These results showed that the delivery of pGM-CSF using chitosan complexes could play an accelerating role in the cell proliferation, migration, and wound-healing process.

Keywords:
Wound healing; Chitosan; pGM-CSF; Complexes

Parameter	Scale of measurement
Acute inflammation	0=absent 1=mild 2=moderate 3=marked
Chronic inflammation	0=absent 1=mild 2=moderate 3=marked
Neovascularization	0=histologically similar to adjacent nomeactive dermis 1= increased vascularity 2=markedly increased vascularity
Epithelization	1= absent 2=minimum; less than half the diameter of the wound 3=completely epithelize, thin layer 4= thicker epithelial layer 5= thick epithelium
Cellular content	1= absent 2= dominant inflammatory cells and a few fibroblast 3= inflammatory cells and fibroblast with less 4=dominant fibroblast 5= a small number of fibroblast in dermis
Granulation tissue	1= absent 2= thick layer of wound edge, no wound center 3=less in wound center, mostly in adipose tissue under the epithelium 4= thicker in the surface of the wound
Collagen deposition	1= absent 2= some collagen fibers 3= more

Formulations	Zeta Potential (mV±SD)	Particle Size (nm±SD)
Free pGM-CSF	-13.2±3.2
Chitosan	35 ± 2.83
pH7.4
Chitosan/pGM-CSF 1/1	5.79 ± 1.00	202±4.31
Chitosan/pGM-CSF 2/1	10.1±0.16	262 ± 21.0
Chitosan/pGM-CSF 5/1	15.0 ± 0.60	333 ± 2.47
Chitosan/pGM-CSF 10/1	28.7 ± 0.71	481.6 ± 13.8
pH5.0
Chitosan/pGM-CSF 1/1	9.12 ± 1.41	230 ± 12.11
Chitosan/pGM-CSF 2/1	12.6 ± 1.41	259 ± 16.32
Chitosan/pGM-CSF 5/1	28.3 ± 0.64	409 ± 23.85
Chitosan/pGM-CSF 10/1	31.4±1.76	514 ± 12.3

Universidade de São Paulo, Faculdade de Ciências Farmacêuticas Av. Prof. Lineu Prestes, n. 580, 05508-000 S. Paulo/SP Brasil, Tel.: (55 11) 3091-3824 - São Paulo - SP - Brazil
E-mail: bjps@usp.br

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[1] *Correspondence: E. Şalva. Department of Pharmaceutical Biotechnology. Faculty of Pharmacy. İnönü University, 44280, Malatya, Turkey. E-mail: emine.salva@inonu.edu.tr. ORCID: https://orcid.org/0000-0002-1159-5850