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In Situ Crosslinked Micelle/Hydrogel Composites for Local and Sustained Delivery of Hydrophobic Anticancer Drugs
- Author(s)
- 박지슬
- Alternative Author(s)
- Ji Seul Park
- Advisor
- 박기동
- Department
- 일반대학원 분자과학기술학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2021-02
- Language
- eng
- Keyword
- Composite; Drug delivery; Hydrogel; Paclitaxel
- Alternative Abstract
- Conventional cancer treatments containing surgery, radiation therapy, and systemic chemotherapy have been performed for the past several decades. However, surgical limitations, undesired side effects on normal cells, and poor water solubility of strong anti-cancer drugs remain challenges. As an alternative method, localized chemotherapy which delivers anti-cancer drugs directly to the target site has gained attention due to the improved drug efficacy and minimized systemic side effects. Furthermore, prolonged release of the chemotherapeutic is also important for the treatment of large tumors and the avoidance of tumor recurrence. Although nanocarriers and in situ forming hydrogels have been widely studied for the localized delivery systems of hydrophobic anti-cancer drugs, they are not sufficient ways to treat cancer due to the low physical stability of particles and hydrophilic nature of the hydrogels. Therefore, the design and formation of a drug carrier with the desired function by combining these two types of materials are drawing attention. Among various particles, Kim and colleagues developed the HRP/H2O2 mediated shell-crosslinked Tetronic-tyramine (Tet-TA) micelles for the enhanced stability (> 4 weeks) and prolonged release of the hydrophobic drugs (~80% cumulative release in 4 days). In this study, we prepared the in situ crosslinked Tet-TA micelle/gelatin hydrogel composites via HRP/H2O2 ¬mediated cross-linking for the sustained delivery of hydrophobic anticancer drugs. Biocompatible-polymers, gelatin, and Tet were modified with phenol moieties and characterized by 1H NMR and UV spectrometer. Paclitaxel (PTX), a hydrophobic anticancer drug, was successfully encapsulated (loading efficiency= 59.9%) in the Tet-TA micelles. PTX-loaded micelle/hydrogel composites were simply formed via enzymatic crosslinking between phenolic groups of gelatin derivatives and Tet-TA. The gelation time varied from 13 to 209 s and could be simply controlled by changing HRP concentrations. The PTX-loaded micelles were enzymatically crosslinked to the hydrogel network restricting the aggregation of the micelles in the composites, increasing the mechanical strength of hydrogels (6636→7351 Pa). The relatively low swelling ratio of the crosslinked micelle/hydrogel composites also indicated the slightly increased crosslinking density. PTX was released from the crosslinked micelle/hydrogel composites in a sustained manner (~47%) for 28 days in vitro. In vitro cytotoxicity test proved the excellent cytocompatibility of the composite systems and improved drug efficacy against cancer cells. In conclusion, we can suggest the in situ crosslinked micelle/hydrogel composite system as a promising local hydrophobic anti-cancer drug carrier for improved cancer treatment.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Molecular Science and Technology > 3. Theses(Master)
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