Design of Oral Drug Delivery Systems for Therapeutic Proteins

الموضوعات

علوم تطبيقية وتكنولوجية

الملخص

The occurrence of inflammatory bowel diseases (IBD) involves the gastrointestinal (GI) tract inflammation. Oxidative stress, overproduction of reactive oxygen species (ROS), plays an important role in risks associated with IBD. The imbalance or altered function of immune cells may also lead to IBD. Catalase has massive therapeutic potential by scavenging hydrogen peroxide which is one of ROS; though, in vivo application is particularly limited if orally administered. Here, we introduced an alginate-based oral drug delivery system that protected catalase from the harsh conditions of the GI tract, released it in the small intestine environment, and enhanced its absorption via M cells, highly specialized epithelium cells in the small intestine. Firstly, catalase was encapsulated in alginate: polygalacturonic acid/ pectin microparticles via the ionotropic gelation method with more than 90% encapsulation efficiency. Alginate-based microparticle released catalase in a pH-dependent manner. For example, alginate-polygalacturonic acid microparticle (60 wt% Alg:40 wt% Gal) released 79.5 ± 2.4 % of encapsulated catalase at pH 9.1 in 3 h, while only 9.2 ± 1.5 % of catalase was released at pH 2.0. Even catalase in microparticles (60 wt% Alg:40 wt% Gal) was exposed to pH 2.0 followed by pH 9.1, it still retained 81.0 ± 11.3 % enzyme activity compared to enzyme activity of catalase in microparticles prior to the pH treatment. We then investigated the efficiency of RGD conjugation to catalase on the uptake by M-like cells, the co-culturing of human epithelial colorectal adenocarcinoma; Caco-2 cells and B lymphocyte; Raji cells. RGD conjugation to catalase enhanced the uptake by M-cells with 87.6 ± 0.8% RGD-catalase, whereas, 11.5 ± 9.2% of unconjugated catalase was transported across M- cells. As a result, RGD-catalase protected M-cells more efficiently from the cytotoxicity of H2O2, one of reactive oxygen species. Based on the protection, release, and absorption of therapeutic proteins from the harsh pH conditions, alginate-based oral drug delivery systems will have several utilizations for drugs that are simply degraded in the GI tract.

روابط وملفات

التعريف والنوع

رقم الوثيقة

fe3091ab-cbc8-4c7e-ad66-051fac683cb7

رقم العقد

0

نوع الوسائط

Crawler

نوع المحتوى

الرسائل العلمية

صيغة المصدر

رسائل ماجيستير

نوع الملف

pdf text

أسماء الملفات

2282723_1.pdf

بيانات النشر

ألقاب المؤلفين

[{"name_ar":"Nouran Ahmed Farid","title_ar":"اعداد","title_en":"Preparation"},{"name_ar":"Sung Mun Lee","title_ar":"اشراف","title_en":"Supervision"}]

اللغة

English

المصدر والدورية

اسم المصدر

Design of Oral Drug Delivery Systems for Therapeutic Proteins

المحتوى والصفحات

عدد الصفحات

0

كلمات الباحثين

Oral Drug Delivery, Polymeric microparticles,Alginate, Catalase, Reactive Oxygen Species, RGD peptides,M cells

إشراف وإعداد

الإشراف

Sung Mun Lee

الإعداد

Nouran Ahmed Farid

الاقتباسات الببليوغرافية