Malays. J. Anal. Sci. Volume 29 Number 3 (2025): 1324

Research Article

Synthesis and characterisation of citric acid-based disulphide polymers for potential drug delivery application

Ong Huey Ching, Adibah Izzati Daud, and Siti Nur Aishah Mat Yusuf^*

Faculty of Chemical Engineering & Technology, Universiti Malaysia Perlis, Kompleks Pusat Pengajian Jejawi (KPPJ 3), Kawasan Perindustrian Jejawi, 02600, Arau, Perlis, Malaysia

^*Corresponding author: nuraishahyusuf@unimap.edu.my

Received: 18 September 2024; Revised: 25 May 2025; Accepted: 3 June 2025 ; Published: 29 June 2025

Abstract

Polymers containing disulphide bonds have recently been recognised as an invaluable material in delivering anticancer drugs. These polymers show promise in overcoming the non-targeted distribution of drugs in the upper parts of the gastrointestinal tract before reaching the targeted disease site. Their redox-sensitive nature and resistance to the harsh environment of the stomach and small intestine make polymers containing disulphide bonds a potential solution. The objective of this study was to synthesise and characterise citric acid-based disulphide polymer. The monomer was synthesised using amide coupling reaction between citric acid and 2-(tritylthio)ethaneamine (1) utilising a two-step synthesis method. The s-trityl group of N¹,N²,N³-tris(2-(tritylthio)ethyl)-2-((2(tritylthio)ethyl)amino)propane-1,2,3-tricarboxamide (2) was deprotected using trifluoroacetic acid and triethylsilane to produce N¹,N²,N³-tris(2-mercaptoethyl)-2-((2-mercaptoethyl)amino)propane-1,2,3-tricarboxamide (3). The successful synthesis of three compounds was confirmed using FT-IR, NMR, and CHNS analysis. Subsequently, three disulphide polymers (P10, P15, and P51) were synthesised by the oxidative polymerisation of various molar ratios of tetra-thiol monomers and dithiol monomers. The polymers were analysed using spectrometric analysis (FT-IR, FE-SEM-EDX, SEM mapping, and Raman spectrometry). The FT-IR results indicated the presence of the C–O–C stretch peak of dithiol monomer in polymers P15 and P51, whereas it was absent in polymer P10 since polymerisation involves only tetra-thiol monomer. According to SEM analysis, polymers P51 resulted in rougher and coarser surfaces, but polymer P15 has more porous surfaces. The EDX and mapping findings indicated a uniform distribution of carbon, oxygen, sulphur, and nitrogen throughout all polymers. These findings indicated that the polymerisation of all disulphide bond polymers occurred homogeneously.

Keywords: synthesis, characterisation, citric acid, disulphide polymer, oral targeted drug delivery system

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