Harnessing silk fibroin microparticles for metformin delivery: A novel approach to treating corneal neovascularization       
Yazarlar (13)
Heybet Kerem Polat
T.C. Sağlık Bakanlığı,, Türkiye
Eren Aytekin
Hacettepe Üniversitesi, Türkiye
Nasıf Fatih Karakuyu
Süleyman Demirel Üniversitesi, Türkiye
Yağmur Akdağ Çaylı
Hacettepe Üniversitesi, Türkiye
Semih Çalamak
Lokman Hekim Üniversitesi, Türkiye
Nazire Demirci
Private Atanur Eye Hospital, Türkiye
Sedat Ünal
Erciyes Üniversitesi, Türkiye
Dr. Öğr. Üyesi Nihat KURT Tokat Gaziosmanpaşa Üniversitesi, Türkiye
Rumeysa Çırak
Hacettepe Üniversitesi, Türkiye
Eda Erkan
Hacettepe Üniversitesi, Türkiye
Behzad Mokhtare
Dicle Üniversitesi, Türkiye
Ali Sefa Mendil
Erciyes Üniversitesi, Türkiye
Sibel Bozdağ Pehlivan
Hacettepe Üniversitesi, Türkiye
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale
Dergi Adı Journal of Drug Delivery Science and Technology
Dergi ISSN 1773-2247 Wos Dergi Scopus Dergi
Dergi Tarandığı Indeksler SCI-Expanded
Dergi Grubu Q1
Makale Dili İngilizce
Basım Tarihi 06-2024
Cilt No 96
Sayı 1
DOI Numarası 10.1016/j.jddst.2024.105625
Makale Linki https://doi.org/10.1016/j.jddst.2024.105625
Özet
Corneal neovascularization (CV) poses significant challenges in ophthalmology, often leading to impaired vision and discomfort. Silk fibroin microparticles have emerged as promising candidates for drug delivery applications, owing to their biocompatibility, biodegradability, and controlled release characteristics. In the current research, metformin-loaded silk microparticles were developed, and their potential for treating corneal neovascularization was evaluated. Silk microparticles were prepared using silk fibroin and polyvinyl alcohol (PVA) at various weight ratios, facilitating phase separation to create a porous structure conducive to drug loading. Metformin (MT), a widely used antidiabetic agent with potential anti-angiogenic properties, was incorporated into the silk microparticles at different concentrations. The formulation termed TB (0.3 % MT loaded Microparticles) emerged as the most promising candidate was identified through comprehensive in vitro evaluations. In in vitro cytotoxicity studies, it was determined that all formulations provided cell viability above 80%, however, in permeability studies and encapsulation efficiency studies, TB was determined to be more effective than other formulations. TB demonstrated a particle size of approximately 8.9 ± 3.6 μm and an encapsulation efficiency of 96.3 ± 2.1%. In vitro release studies revealed that TB exhibited a burst release of 62% within the initial two days, followed by sustained release over a period of 14 days, consistent with Peppas-Sahlin kinetics. Mathematical modeling further corroborated the diffusion mechanism underlying drug release from TB microparticles. In vivo studies on rats and histochemical analyzes on corneas showed that TB exhibited efficacy comparable to dexamethasone, a standard treatment for CV, despite being administered once daily. Histological analyses of corneal tissues revealed reduced neovascularization and inflammation in the TB-treated group, underscoring its therapeutic potential. Overall, our findings highlight the promise of metformin-loaded silk fibroin microparticles as a novel therapeutic approach for managing CV, offering sustained drug release and enhanced efficacy in treating this challenging ocular condition.
Anahtar Kelimeler
Corneal neovascular | Metformin | Microparticle | Peppas-sahlin | Silk fibroin