dc.contributor.advisor |
Mhanna, Rami |
dc.contributor.advisor |
Jaffa, Ayad |
dc.contributor.author |
Fahs, Duaa |
dc.date.accessioned |
2021-02-07T04:57:33Z |
dc.date.available |
2021-02-07T04:57:33Z |
dc.date.issued |
2/7/2021 |
dc.identifier.uri |
http://hdl.handle.net/10938/22218 |
dc.description |
Dr. Firas Kobaissy
Dr. Ali Tehrani |
dc.description.abstract |
Introduction: Diabetic foot ulcers (DFUs) are a complication to diabetes mellitus that
cause 85% of all amputations worldwide and pose an annual economic burden of $15
billion. The wound healing process is altered in DFU patients partly due to the
deficiency of growth factors (GF) such as insulin-like growth factor-1 (IGF-1). To
address the problem of GF deficiency in DFU, we engineered double emulsion
nanoparticles (NPs) using heparin-mimetic alginate sulfate (AlgSulf) for the
encapsulation and sustained release of IGF-1 to promote wound repair and decrease
inflammation in the wound microenvironment.
Methods: NPs were synthesized with an AlgSulf core and polycaprolactone (PCL) shell
via the solvent evaporation technique. The NPs were characterized for their size, zeta
potential, and polydispersity index using dynamic light scattering, and morphology
using scanning electron microscopy. IGF-1 encapsulation efficiency (EE) and release
rate were analyzed using enzyme-linked immunosorbent assay (ELISA). The NPs’
cytotoxicity was assessed on human keratinocyte (HaCaT) cell line using trypan blue
and MTT assays. Cellular uptake of the NPs was evaluated by assessing the
fluorescence intensity of HaCaT cells treated with fluorescently labeled Alg or AlgSulf
loaded NPs. The ability of NPs to reduce inflammation was measured by quantifying
the mRNA and protein expression levels of IL-6 inflammatory marker using qRT-PCR
and ELISA.
Results: NPs with AlgSulf of a degree of sulfation (DS=2) AlgSulf2.0/PCL had the
smallest average size and lowest zeta potential (p<0.05). IGF-1 EE was higher in
AlgSulf NPs compared to non-sulfated Alg-based NPs (98.59% ± 0.48 and 97.43% ±
2.83 AlgSulf0.8/PCL and AlgSulf2.0/PCL NPs, respectively compared to 95.56% ±
1.89 for AlgSulf0.0). Bare AlgSulf2.0/PCL NPs showed no cytotoxic effect up to 100
µg/mL after 72 hours as shown by trypan blue and up to 100 µg/mL after 48 hours as
shown by MTT. The cellular uptake was significantly increased with time up to 24
hours (p<0.001) for Alg/PCL NPs and showed an increasing trend over 24 hours for
AlgSulf2.0/PCL NPs (p=0.352). All NPs showed a similar trend in reducing IL-6 in the
inflamed media.
Conclusion: Heparin-mimetic IGF-1 loaded AlgSulf NPs represent a novel approach for
improving DFUs healing. The developed NPs may also be used for the delivery of other
heparin-binding GFs exhibiting broad applications in the therapeutics domain. |
dc.language.iso |
en_US |
dc.subject |
Nanoparticles, Double emulsion, Diabetes, Diabetic foot ulcers, Alginate Sulfate, Heparin mimetic, Anti-inflammatory |
dc.title |
HEPARIN-MIMETIC ALGINATE SULFATE/POLYCAPROLACTONE DOUBLE EMULSION NANOPARTICLES FOR ENHANCED INSULIN-LIKE GROWTH FACTOR (IGF-1) DELIVERY AND DIABETIC WOUND HEALING APPLICATIONS |
dc.type |
Thesis |
dc.contributor.department |
Department of Biomedical Engineering |
dc.contributor.faculty |
Maroun Semaan Faculty of Engineering and Architecture |
dc.contributor.institution |
American University of Beirut |