Sulfated alginate/polycaprolactone double-emulsion nanoparticles for enhanced delivery of heparin-binding growth factors in wound healing applications

Batoul Maatouk; Miran A Jaffa; Mia Karam; Duaa Fahs; Wared Nour-Eldine; Anwarul Hasan; Ayad A Jaffa; Rami Mhanna

doi:10.1016/j.colsurfb.2021.112105

Sulfated alginate/polycaprolactone double-emulsion nanoparticles for enhanced delivery of heparin-binding growth factors in wound healing applications

Colloids Surf B Biointerfaces. 2021 Dec:208:112105. doi: 10.1016/j.colsurfb.2021.112105. Epub 2021 Sep 15.

Authors

Batoul Maatouk¹, Miran A Jaffa², Mia Karam¹, Duaa Fahs¹, Wared Nour-Eldine³, Anwarul Hasan⁴, Ayad A Jaffa⁵, Rami Mhanna⁶

Affiliations

¹ Biomedical Engineering Program, Maroun Semaan Faculty of Engineering and Architecture, American University of Beirut, Beirut 1107 2020, Lebanon; Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, P.O.Box 11-0236, Beirut, Lebanon.
² Epidemiology and Population Health Department, Faculty of Health Sciences, American University of Beirut, P.O.Box 11-0236, Beirut, Lebanon.
³ Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, P.O.Box 11-0236, Beirut, Lebanon.
⁴ Department of Mechanical and Industrial Engineering at Qatar University, P.O. Box 2713, Doha, Qatar.
⁵ Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, P.O.Box 11-0236, Beirut, Lebanon. Electronic address: aj24@aub.edu.lb.
⁶ Biomedical Engineering Program, Maroun Semaan Faculty of Engineering and Architecture, American University of Beirut, Beirut 1107 2020, Lebanon. Electronic address: rm136@aub.edu.lb.

PMID: 34536674
DOI: 10.1016/j.colsurfb.2021.112105

Abstract

Diabetic foot ulcers (DFUs) that are not effectively treated could lead to partial or complete lower limb amputations. The lack of connective tissue growth factor (CTGF) and insulin-like growth factor (IGF-I) in DFUs results in limited matrix deposition and poor tissue repair. To enhance growth factor (GF) availability in DFUs, heparin (HN)-mimetic alginate sulfate/polycaprolactone (AlgSulf/PCL) double emulsion nanoparticles (NPs) with high affinity and sustained release of CTGF and IGF-I were synthesized. The NPs size, encapsulation efficiency (EE), cytotoxicity, cellular uptake and wound healing capacity in immortalized primary human adult epidermal cells (HaCaT) were assessed. The sonication time and amplitude used for NPs synthesis enabled the production of particles with a minimum of 236 ± 25 nm diameter. Treatment of HaCaT cells with up to 50 μg mL^-1 of NPs showed no cytotoxic effects after 72 h. The highest bovine serum albumin EE (94.6 %, P = 0.028) and lowest burst release were attained with AlgSulf/PCL. Moreover, cells treated with AlgSulf/CTGF (250 ng mL^-1) exhibited the most rapid wound closure compared to controls while maintaining fibronectin synthesis. Double-emulsion NPs based on HN-mimetic AlgSulf represent a novel approach which can significantly enhance diabetic wound healing and can be expanded for applications requiring the delivery of other HN-binding GFs.

Keywords: Biomarkers; Connective tissue growth factor; Diabetic foot ulcers; Insulin-like growth factor; Wound healing.

MeSH terms

Alginates
Diabetic Foot*
Emulsions
Heparin
Humans
Nanoparticles*
Polyesters
Sulfates
Wound Healing

Substances

Alginates
Emulsions
Polyesters
Sulfates
polycaprolactone
Heparin