Synthesis and characterization of PEG-b-PLA copolymer for the targeted nano drug delivery systems

Abstract

Amphiphilic block copolymers (ABC) have many advantages due to their structure and are important in the biomedical field as they have both hydrophobic and hydrophilic polymer contents together. These polymers which can be synthesized in a different size, properties, have a wide range of uses and therefore have expanded their field of study. They are used in pharmaceutical applications and especially in the formation of nanoparticles. Due to their non-toxic properties, these block copolymers can be modified with various molecules to act as carriers for drug delivery systems. In this study, amphiphilic block copolymers consist of polyethylene glycol (PEG) and polylactic acid (PLA) were synthesized to prepare nanoparticles via different nanoparticle studies. Polyethylene glycol (PEG) is a significant polymer with its biocompatibility in many biological and medical applications. Targeted amphiphilic block copolymers are one of these usage areas. Within the scope of this thesis, PEG, which was used as a hydrophilic block, has been given the desired end function by a series of reactions from the hydroxyl end group. Maleic anhydride which is unlikely to self-polymerize is involved in grafting reactions under free-radical conditions. In this context, the graft reaction of polyethylene glycol with maleic anhydride has been performed to ensure that PEG to be used as the hydrophilic block has branch groups for the desired properties. Poly(lactic acid) (PLA) which is approved by the Food and Drug Administration (FDA) to use in many types of applications has been noted as one of the most important biocompatible and biodegradable polymers to form amphiphilic block copolymers. PLA, which was used as a hydrophobic block, was synthesized by using ring-opening polymerization (ROP) in order to obtain proper chain length with a low PDI. Both functional PEG and PLA segments were gathered via copper-catalyzed azide-alkyne cycloaddition (CuAAC) namely click chemistry to form the amphiphilic block copolymer. The synthesized amphiphilic block copolymer was characterized by Nuclear Magnetic Resonance (NMR) and Fourier Transform Infrared Spectroscopy (FTIR) and Gel Permeation Chromatography (GPC). In the second part, nanoparticle studies and also drug loading studies were performed with synthesized (mPEG-g-MA)-b-PLA copolymer and two different hydrophobic drugs. The size analysis of the polymeric nanoparticles was performed by dynamic light scattering (DLS) and the nanoparticle sizes and polydispersity ındex (PDI) in different media were determined. In the continuation of the study, it is aimed that the polymeric nanoparticle system will gain targeting property with peptide-based targeting agents and thus the system will be introduced as a targeted nano drug delivery system to the literature.