HEPARINMIMETIC ALGINATE SULFATE/POLYCAPROLACTONE DOUBLE EMULSION NANOPARTICLES FOR ENHANCED INSULINLIKE GROWTH FACTOR (IGF1) DELIVERY AND DIABETIC WOUND HEALING APPLICATIONS

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الملخص

Introduction: Diabetic foot ulcers (DFUs) are a complication to diabetes mellitus thatcause 85% of all amputations worldwide and pose an annual economic burden of $15billion. The wound healing process is altered in DFU patients partly due to thedeficiency of growth factors (GF) such as insulin-like growth factor-1 (IGF-1). Toaddress the problem of GF deficiency in DFU, we engineered double emulsionnanoparticles (NPs) using heparin-mimetic alginate sulfate (AlgSulf) for theencapsulation and sustained release of IGF-1 to promote wound repair and decreaseinflammation in the wound microenvironment.Methods: NPs were synthesized with an AlgSulf core and polycaprolactone (PCL) shellvia the solvent evaporation technique. The NPs were characterized for their size, zetapotential, and polydispersity index using dynamic light scattering, and morphologyusing scanning electron microscopy. IGF-1 encapsulation efficiency (EE) and releaserate were analyzed using enzyme-linked immunosorbent assay (ELISA). The NPs’cytotoxicity was assessed on human keratinocyte (HaCaT) cell line using trypan blueand MTT assays. Cellular uptake of the NPs was evaluated by assessing thefluorescence intensity of HaCaT cells treated with fluorescently labeled Alg or AlgSulfloaded NPs. The ability of NPs to reduce inflammation was measured by quantifyingthe mRNA and protein expression levels of IL-6 inflammatory marker using qRT-PCRand ELISA.Results: NPs with AlgSulf of a degree of sulfation (DS=2) AlgSulf2.0/PCL had thesmallest average size and lowest zeta potential (p<0.05). IGF-1 EE was higher inAlgSulf 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 100µg/mL after 72 hours as shown by trypan blue and up to 100 µg/mL after 48 hours asshown by MTT. The cellular uptake was significantly increased with time up to 24hours (p<0.001) for Alg/PCL NPs and showed an increasing trend over 24 hours forAlgSulf2.0/PCL NPs (p=0.352). All NPs showed a similar trend in reducing IL-6 in theinflamed media.Conclusion: Heparin-mimetic IGF-1 loaded AlgSulf NPs represent a novel approach forimproving DFUs healing. The developed NPs may also be used for the delivery of otherheparin-binding GFs exhibiting broad applications in the therapeutics domain.

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التعريف والنوع

رقم الوثيقة: fe857c97-65ce-4ccf-a234-284290597ced
رقم العقد: 0
نوع الوسائط: Crawler
نوع المحتوى: الرسائل العلمية
صيغة المصدر: رسائل ماجيستير
نوع الملف: pdf text
أسماء الملفات: 2025889_1.pdf

بيانات النشر

ألقاب المؤلفين: [{"name_ar":"DUAA BASSAM FAHS","title_ar":"اعداد","title_en":"Preparation"}]
اللغة: English

المصدر والدورية

اسم المصدر: HEPARINMIMETIC ALGINATE SULFATE/POLYCAPROLACTONE DOUBLE EMULSION NANOPARTICLES FOR ENHANCED INSULINLIKE GROWTH FACTOR (IGF1) DELIVERY AND DIABETIC WOUND HEALING APPLICATIONS

المحتوى والصفحات

عدد الصفحات: 0

إشراف وإعداد

الإعداد: DUAA BASSAM FAHS

الاقتباسات الببليوغرافية

APA

DUAA BASSAM FAHS. (2021). HEPARINMIMETIC ALGINATE SULFATE/POLYCAPROLACTONE DOUBLE EMULSION NANOPARTICLES FOR ENHANCED INSULINLIKE GROWTH FACTOR (IGF1) DELIVERY AND DIABETIC WOUND HEALING APPLICATIONS. أطروحة(رسائل ماجيستير). كلية الطب-الجامعة الأمريكية في بيروتكلية مارون سمعان للهندسة والعمارة-الجامعة الأمريكية في بيروت. لبنان.

MLA

DUAA BASSAM FAHS. HEPARINMIMETIC ALGINATE SULFATE/POLYCAPROLACTONE DOUBLE EMULSION NANOPARTICLES FOR ENHANCED INSULINLIKE GROWTH FACTOR (IGF1) DELIVERY AND DIABETIC WOUND HEALING APPLICATIONS. 2021. كلية الطب-الجامعة الأمريكية في بيروتكلية مارون سمعان للهندسة والعمارة-الجامعة الأمريكية في بيروت، رسائل ماجيستير.