Summary of Material science doctoral thesis: Improving the effective delivery of cisplatin anti cancer drug of dendrimer nanocarrier

Research purpose: Preparation and characterization of nanocarrier systems for drug delivery system based on the modification of dendrimer (PAMAM) with biocompatible surfaces such as PNIPAM and PAA to improve the capping cisplatin.
Nội dung trích xuất từ tài liệu:
Summary of Material science doctoral thesis: Improving the effective delivery of cisplatin anti cancer drug of dendrimer nanocarrier MINISTRY OF EDUCATION AND VIETNAM ACADEMY OF SCIENCE AND TRAINING TECHNOLOGY GRADUATE UNIVERSITY OF SCIENCE AND TECHNOLOGY NGUYEN NGOC HOA IMPROVING THE EFFECTIVE DELIVERY OF CISPLATIN ANTI CANCER DRUG OF DENDRIMER NANOCARRIER Field of Study: Polymer and Composite Code: 9 44 01 25 SUMMARY OF MATERIAL SCIENCE DOCTORAL THESIS HO CHI MINH, 2020 The thesis was completed at Institute of Applied Materials Science - Graduate University of Science and Technology Vietnam Academy of Science and Technology Supervisor 1: Prof., Dr. Nguyen Cuu Khoa Supervisor 2: Assoc., Prof., Dr. Tran Ngoc Quyen Reviewer 1: … Reviewer 2: … Reviewer 3: …. The thesis shall be defended in front of the Thesis Committee at Academy Level at Institute of Applied Materials Science - Vietnam Academy of Science and Technology At...... hour....... date...... month....., 2021 The thesis can be found at: - The National Library of Vietnam - The Library of Graduate University of Science and Technology 1 INTRODUCTION 1. The necessity of the thesis Denndrimers were first introduced during the period 1970–1990 by two different groups : Buhleier et al and Tomalia et al. Dendrimers are nano-sized, radially symmetric molecules with well-defined, homogeneous, and monodisperse structure consisting of tree-like arms or branches. Dendrimers are nearly mono-disperse macromolecules that contain symmetric branching units built around a small molecule or a linear polymer core. Dendrimers are hyperbranched macromolecules with a carefully tailored architecture, the end-groups (i.e., the groups reaching the outer periphery), which can be functionalized, thus modifying their physicochemical or biological properties. Dendrimers are designed to drugs delivery to enhance the pharmacokinetics and biological distribution of the drug and to enhance its target ability. Due to their exquisite structure, drug molecules are instantly capped with dendrimer molecules by means of physical adsorption, electrostatic interaction, covalent binding with the peripheral functional groups, or encapsulating inside the dendrimeric crevices. The dendrimeric crevices are usually hydrophobic, which can encapsulate the drug molecule by means of hydrophobic. Further, the high density of peripheral groups of multifunctional nature (amine, NH2 or carboxylate COO-) allows to establish electrostatic interaction with drug and then bring them to the target site. Cisplatin is one of the most effective anticancer agents widely used in the treatment of solid tumors. It has been extensively used for the cure of different types of neoplasms including head and neck, lung, ovarian, leukemia, breast, brain, kidney and testicular cancers. In general, cisplatin and other platinum-based compounds are considered as cytotoxic drugs which kill cancer cells by damaging DNA, inhibiting DNA synthesis and mitosis, and inducing apoptotic cell death. However, because of drug resistance and numerous undesirable side effects such as severe kidney problems, allergic reactions, decrease immunity to infections, gastrointestinal disorders, hemorrhage, and hearing loss especially in younger patients, other platinum- containing anti-cancer drugs such as carboplatin, oxaliplatin and others, have also been used. Furthermore, combination therapies of cisplatin with other drugs have been highly considered to overcome drug-resistance and reduce toxicity. In the last decade, an alternative strategy following the revolution of nanotechnology has been a shift in focus from platinum complex design to Cisplatin carriers in order to enhance anticancer activity and reduce its side-effects. Among numerous Cisplatin delivery methods, Cisplatin conjugated carriers have been proven as a promising option. Cisplatin can be attached appropriately to the nano-devices containing ester or amide linkages or carboxylate connectivity. These interactions can later be hydrolyzed inside the cell allowing drugs to accumulate in the tumor site. Generally, the conjugate between Cisplatin and carriers revealed an improved efficacy of the platinum drug in cancer treatment compared to physical encapsulation. In this thesis, we modify the surface functional groups of PAMAM dendrimers to enhance the drug delivery capacity of these carriers. 2. Research purpose Preparation and characterization of nanocarrier systems for drug delivery system based on the modification of dendrimer (PAMAM) with biocompatible surfaces such as PNIPAM and PAA to improve the capping cisplatin 3. Research content 2 - Synthesizing the derivative PAMAM dendrimer (PAMAM dendrimer - Poly(N- isopropylacrylamide), PAMAM dendrimer - Poly acrylic acid). - Evaluating their chemical structure and grafting degree - Evaluating the capping cisplatin ability of PAMAM dendrimer and their derivative such as PAMAM dendrimer - Poly(N-isopropylacrylamide), PAMAM dendrimer - Poly acrylic acid. - Analyzing the structure of the complex carrier – drug and evaluating the release of cisplatin from carrier. - Identifying the cytotoxicity of PAMAM dendrimer and their derivative CHAPTER 1. OVERVIEW 1.1. Introduction to dendrimer and ...