Kolorektal Kanserlerin Lokal Tedavisinde Oral Uygulanabilen Nanopartiküler İlaç Taşıyıcı Sistem Geliştirilmesi ve İn Vitro/İn Vivo Değerlendirilmesi

Abstract

Anticancer drugs need to be administered via the parenteral route because of limitations arising from their physicochemical properties. Non-specific biodistribution and difficulty in parenteral administration adversely affect patient compliance and efficacy of treatment. In this study, it is aimed to develop a drug delivery system that can be administered orally, which provides a local treatment opportunity for the tumor region by delivering the active substance to the colon in the treatment of colorectal cancer. Camptothecin, known for its potent anticancer activity against colon cancer cells, but limited in clinical practice due to poor solubility and stability under physiological conditions, has been selected as the model drug. Nanoparticles of the amphiphilic cyclodextrins (6-O-CAPRO-β-CD and Poly-β-CD-C6) intended to be degraded by colonic bacteria to release the drug in the colon were prepared and (6-O-CAPRO-β-CD) nanoparticles coated with chitosan (CS) and polyethyleneimine (PEI) polymers to give positive surface charge. Blank and drug loaded nanoparticles were prepared by nano-precipitation method and their in vitro characterization, release profiles in gastrointestinal fluids, physical stability, interaction with mucin and penetration to mucus layer were performed. The safety of nanoparticles (L929), intestinal permeability (Caco-2) and anticancer activities (HT-29) were evaluated by in vitro cell culture studies. In vivo studies and in vivo imaging studies were performed with nanoparticles (Poly-β-CD-C6) which were found to have optimum properties during in vitro studies. Conclusion, it has been shown that with camptothecin loaded Poly-β-CD-C6 nanoparticles, an orally administered nanoparticulate drug delivery system can deliver the drug to the tumor area localized in the colon and provides an effective treatment for colorectal cancers via the oral route.