Design of Oral Drug Delivery Systems for Therapeutic Proteins

  • Nouran Ahmed Farid

Student thesis: Master's Thesis

Abstract

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.
Date of AwardJul 2022
Original languageAmerican English

Keywords

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

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