Siti Amirah Haji Yussof | ALES Graduate Seminar

Date(s) - 14/08/2023
10:00 am - 11:00 am

Event details: A graduate exam seminar is a presentation of the student’s final research project for their degree.
This is an ALES MSc Final Exam Seminar by Siti Amirah Haji Yussof. This seminar is open to the general public to attend.

MSc with Dr. Aman Ullah.

Thesis Topic: Synthesis of amphiphilic block copolymers from fatty acids as potential nano drug delivery system


Conventional drug delivery methods are inefficient in localized delivery of therapeutic agents, especially those with poor water solubility, causing unwanted side effects, poor bioavailability, in vivo instability, poor solubility, and poor absorption in the body. This consequently attracted wide attention in biomedical research for the development of new drug delivery systems with hopes of creating a more efficient and controlled method of drug release and delivery for various ailments.

For the delivery of hydrophobic drugs, micelle structures which is typically formed from amphiphilic systems such as block copolymers has been identified as one of the most promising therapeutic agent’s carriers. Due to increasing environmental concerns as well as other attractive properties such as biocompatibility, biodegradability, non-toxicity, and abundant availability, the use of naturally occurring materials for the synthesis of potential drug delivery system has been gaining interest over the years as alternatives to synthetic sources. Studies on amphiphilic block copolymers based on fatty acids as a potential drug delivery system has not been extensively investigated.

Therefore, in this project, Lauric and Palmitic acid were transformed into monomers and polymerized into block copolymers via microwave-assisted reversible addition-fragmentation chain transfer agent (RAFT) polymerization to investigate its synthesis feasibility and discover the challenges faced during synthesis process. The fatty acids were first functionalized with hydroxy ethyl acrylate (HEA) to attach the desired active vinyl group in preparation for polymerization. N,N-Dimethylacrylamide (DMA) was then polymerized with the RAFT agent (CTA) to form the homopolymer which acted as the macro chain transfer agent (mCTA). The mCTA homopolymer was then reacted with the fatty acid monomer to produce the amphiphilic block copolymer. Fatty acids monomers, DMA homopolymer and block copolymers synthesized were analyzed using Fourier transform infrared spectroscopy (FTIR), gel permeation chromatography (GPC), and proton nuclear magnetic resonance (1H NMR).

Fatty acids monomers synthesized were palmitic acid monomer (PAM), lauric acid monomer (LAM). The LAM monomers were synthesized using coupling agent N,N′-dicyclohexylcarbodiimide (DCC) named as LAM A, while LAM B monomer was synthesized using coupling agent 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC). The FTIR and 1H NMR analyses indicated successful functionalization of HEA to fatty acids.

The analysis of mCTA using FTIR, 1H NMR, and GPC, confirmed reaction of DMA with RAFT agent. However, the GPC analysis shows a polymer with high dispersity of 1.5, indicating that the RAFT polymerization reaction was not controlled. The molecular weight was lower than expected from literature, which indicated possible early termination of polymerization due to presence of inhibitors/loss of initiators.

The two block copolymers (A&B) were then synthesized using monomers LAM A & LAM B respectively. Block copolymer A characterization indicates oligomerization, possibly due to impurities in monomers inhibiting reaction or leading to different products. The block copolymer B analysis using FTIR indicated successful synthesis, however GPC results indicate presence of some impurities from unreacted components. A polymer with a Mw of 2249 g/mol was achieved.

In conclusion, attempts were made to prepare monomers from lipids and their polymerization to make block copolymers although low molecular masses were obtained due to presence of impurities. The project highlighted the importance of efficient purification procedures, solvent suitability knowledge, precision and accuracy in experimental work, and comprehensive literature research to ensure successful reaction and desired products obtained. Although block copolymers can be synthesized via this method, it is worth mentioning that synthesis of block copolymers via this method can be time consuming to fine tune to obtain pure final block copolymers products with high molecular mass.