Development and Characterisation of Diblock Copolymeric Micelle Formulations Containing Protein Structured Active Ingredients and Demonstration of In-vitro/Ex-vivo Efficacy
Project no. 32139 · Status: Kapanmış (Yayın bekleniyor) · 2024
Summary
<p>Cancer is a serious global health problem with high morbidity and mortality rates. Although conventional chemotherapeutic agents are frequently preferred, they show limiting effects such as systemic toxicity and resistance to treatment.</p><p>Epigallocatechin-3-gallate (EGCG) is the main catechin obtained from green tea leaves. The anticancer and cancer preventive effects of EGCG, known for its strong antioxidant capacity, have been widely reported in the literature. However, it has low chemical stability and needs to be formulated with drug delivery systems to increase its bioavailability.</p><p>Peptide and protein-based biopharmaceuticals have high target selectivity thanks to their specific binding sites (domains). This feature results in minimal off-target effects and low toxicity. Thrombospondin-1 (TSP-1), an endogenous glycoprotein, shows antiangiogenic and antimetastatic effects and has been shown to produce synergistic pharmacodynamic effects when used in combination with some chemotherapeutics.</p><p>In this project, EGCG loaded mPEG-PLA copolymeric micelles coated with PVA-TSP-1 complex were developed to encapsulate EGCG in the micelles and prevent its degradation due to oxidation. By coating the micelles with PVA-TSP-1 complex, anticancer and antiangiogenesis effects as well as an increase in stability and cellular binding were observed.</p><p>In cell culture studies, it has been shown that the formulation has a lethal effect on cancer cells, while its toxic effects on healthy cells are much less.</p><p>In the CAM study, it was revealed that the formulation applied to egg embryos with a cancer model caused the cancer cells to shrink and fail to maintain their integrity, while the vascularisation in cancer cells decreased.</p>