Publication: CBD loaded halomonas levan hydrogels for prevention of medication related osteonecrosis of the jaw (MRONJ)
Abstract
İlaca bağlı olarak çene kemiklerinde görülen osteonekrosis (MRONJ), hastaların hayat kalitesini ağrı, diş gevşemesi, açık yara, ve kemik nekrozu ile düşüren bir hastalıktır. Geçmişte bisfosfonat ve denosumab kullanmış olan insanlar MRONJ riski taşımaktadır. Özen gösterilen ağız hijyeni hastalığı önlemeye yardımcı olmaktadır. Yine de, polimer hidrojel sistemleri bölgeye kontrollü ilaç salınımı sağlayarak hastalığın önlenmesi veya tedavisine yönelik çalışmalara konu olmaktadır. Hücre dışı matriksi taklit eden yapısı olan ve yüksek miktarda su tutabilen hidrojeller, ilaç taşıma sistemi olarak ve hücre adezyonu ve proliferasyonu için uygun bir ortam sağlayarak doku mühendisliğinde kullanılmaktadır. Levan, ꞵ-2,6 bağlı fruktozil kısımları bulunan, çeşitli mikroorganizmalar ve bitkiler tarafından üretilen bir fruktan ekzopolisakkaritidir. Biyouyumluluk özelliği ile eczacılık, kozmetik, ve gıda alanlarında kullanılmaktadır. Kannabidiol (CBD), psikoaktif olmayan, antienflamatuar, ve ağrı kesici özellikleri bulunan, Cannabis sativa bitkisinin içerdiği hidrofobik bir bileşiktir. Bu tez çalışmasında, levan bazlı, 1,4-butandiol diglisidil eter BDDE çapraz bağlanmış hidrojeller geliştirerek mekanik özelliklerini (şişme, jel fraksiyonu, stabilite) incelemek ve CBD ile HOB hücreleri üzerindeki sitotoksisitesini incelemek hedeflenmiştir. Bu doğrultuda, operasyon bölgesinde olası ağrıyı keserek ve hücre proliferasyonunu destekleyerek MRONJ hastalığını engellemek üzere levan ve CBD içeren hidrojeller üretilmiştir. Düzensiz şekildeki boşlukların doldurulmasının kolaylaştırılması için parçalanan hidrojellerin CBD salınım profili, parçacık boyutu, ve polidispersite indeksi incelenmiştir. Öğütülmüş 1:35 levan hidrojeller yüksek jel fraksiyonları ile biyouyumlu ve şekillendirilmesi kolay olarak değerlendirilmiştir. Hidrojelden gerçekleşen CBD salınımı sonuçları HOB hücrelerine toksik olmayan konsantrasyonda seyretmiştir.
Medicine related osteonecrosis of the jaw (MRONJ) is a disease that lowers the life quality of the patients with the pain, teeth loosening, open wound, and necrosis of the bone. People who have used bisphosphonates denosumab in their past have the risk of MRONJ. Careful oral hygiene helps to prevent the disease, however, polymer hydrogel systems are widely studied to prevent or cure the disease by providing a controlled drug release. Biomaterials like hydrogels, which mimic the extracellular matrix (ECM) and can keep a high amount of water, are used as drug delivery systems and in tissue engineering by providing a proper environment for cell adhesion and proliferation. Levan is a fructan exopolysaccharide with ꞵ-2,6 linked fructosyl residues produced by various microorganisms and plants. It is biocompatible and used in pharmaceutics, cosmetics, and food. Cannabidiol (CBD) is a hydrophobic compound of the plant Cannabis sativa and has nonpsychoactive, anti-inflammatory, and pain relief properties. The aim of this thesis was to develop a levan based 1,4-butanediol diglycidyl ether (BDDE) crosslinked hydrogel, examining its mechanical properties (swelling, gel fraction, stability) and cytotoxicity with CBD on HOB cells. For this, the hydrogels that include these two ingredients, were produced to prevent MRONJ by supporting the cell proliferation and relieving the pain in the operation area.CBD release profile, particle size, and polydispersity index of shredded hydrogels were also examined to ease the application to the cavities that have irregular shape. 1:35 ground hydrogels with high gel fraction were found to be biocompatible and easy to shape. CBD release was observed between the non-toxic range of concentrations to HOB.
Medicine related osteonecrosis of the jaw (MRONJ) is a disease that lowers the life quality of the patients with the pain, teeth loosening, open wound, and necrosis of the bone. People who have used bisphosphonates denosumab in their past have the risk of MRONJ. Careful oral hygiene helps to prevent the disease, however, polymer hydrogel systems are widely studied to prevent or cure the disease by providing a controlled drug release. Biomaterials like hydrogels, which mimic the extracellular matrix (ECM) and can keep a high amount of water, are used as drug delivery systems and in tissue engineering by providing a proper environment for cell adhesion and proliferation. Levan is a fructan exopolysaccharide with ꞵ-2,6 linked fructosyl residues produced by various microorganisms and plants. It is biocompatible and used in pharmaceutics, cosmetics, and food. Cannabidiol (CBD) is a hydrophobic compound of the plant Cannabis sativa and has nonpsychoactive, anti-inflammatory, and pain relief properties. The aim of this thesis was to develop a levan based 1,4-butanediol diglycidyl ether (BDDE) crosslinked hydrogel, examining its mechanical properties (swelling, gel fraction, stability) and cytotoxicity with CBD on HOB cells. For this, the hydrogels that include these two ingredients, were produced to prevent MRONJ by supporting the cell proliferation and relieving the pain in the operation area.CBD release profile, particle size, and polydispersity index of shredded hydrogels were also examined to ease the application to the cavities that have irregular shape. 1:35 ground hydrogels with high gel fraction were found to be biocompatible and easy to shape. CBD release was observed between the non-toxic range of concentrations to HOB.