Advanced search
Start date

Synthesis of amphiphilic and thermosensitive block copolymers, and preparation of polymeric mincro/nanoparticles for controlled drug delivery

Full text
Rodolfo Minto de Moraes
Total Authors: 1
Document type: Doctoral Thesis
Press: Lorena.
Institution: Universidade de São Paulo (USP). Escola de Engenharia de Lorena (EEL/ASDI)
Defense date:
Examining board members:
Amilton Martins dos Santos; Fábio Herbst Florenzano; Reinaldo Giudici; Wang Shu Hui; Mauricio Pinheiro de Oliveira
Advisor: Amilton Martins dos Santos

This work describes the synthesis of different types of amphiphilic, thermosensitive and partially biodegradable block copolymers, via different synthetic routes. For the synthesis of the poly(ε-caprolactone)-b-poly(N-isopropylacrylamide) (PCL-b-PNIPAAm) and poly(N-isopropylacrylamide)-b-poly(3-hydroxybutyrate- hydroxyvalerate)-b-poly(N-isopropylacrylamide) (PNIPAAm-b-PHBHV-b-PNIPAAm) block copolymers, Reversible Addition-Fragmentation chain-Transfer polymerization mediated by xanthate RAFT agent (RAFT/MADIX) was evaluated, started with the synthesis of a PCL-based or PHBHV-based macro-RAFT agents (PCL-oEX or PHBHV(oEX)2), followed by chain extension reactions, using NIPAAm as monomer. The block copolymer, poly (N-vinylcaprolactam)-b-poly (ε-caprolactone) (PNVCL-b-PCL), was obtained via the combination of RAFT/MADIX polymerization and ring-opening polymerization techniques. In this context, NVCL based homopolymers functionalized with hydroxyl group, prepared via RAFT/MADIX polymerization, were used as macroinitiators in the ε-CL ring-opening polymerization. A second chemical route was evaluated for the synthesis of these PNVCL-b-PCL, and poly(3-hydroxybutyrate-co-3-hydroxyvalerate)-b-poly(N-vinylcaprolactam) (PHBHV-b-PNVCL) block copolymers, which consisted of the combination of the RAFT/MADIX polymerization mechanism and the 1,3-dipolar cycloaddition reaction between azides and alkynes. In this chemical route, NVCL homopolymers containing azide group, previously prepared via NVCL RAFT/MADIX polymerization, and PCL or PHBHV macrochains containing alkyne-terminal group, were coupled via the 1,3-dipolar cycloaddition reaction between azides and alkynes. The Gel Permeation Chromatography (GPC) analyzes confirmed the efficiency of the macro-RAFT and RAFT agents in controlling the polymerization of NIPAAm and NVCL, respectively. The chemical structures of all the block copolymers were verified by Fourier-Transform Infrared Spectroscopy (FTIR) and Proton Nuclear Magnetic Resonance Spectroscopy (1H NMR) techniques. The thermal properties and crystallinity of these materials were respectively evaluated by the Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD) techniques. Finally, it was observed that the length of the hydrophobic and hydrophilic blocks has an influence in the critical micelle concentration (CMC), in the lower critical solubilization temperature (LCST) of the block copolymer, and also in the hydrodynamic diameter of the micro/nanoparticles obtained from these materials. (AU)

FAPESP's process: 13/03355-4 - Synthesis of biodegradable/biocompatible block copolymers for obtaining polymeric micro-and nanoparticles for controlled drug release
Grantee:Rodolfo Minto de Moraes
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)