Now showing 1 - 4 of 4
  • Publication
    Characterisation and evaluation of trimesic acid derivatives as disulphide cross-linked polymers for potential colon targeted drug delivery
    ( 2017-07-27) ;
    Yoke Mooi Ng
    ;
    Asila Dinie Ayub
    ;
    Asila Dinie Ayub
    ;
    Vuanghao Lim
    Discovery and use of biocompatible polymers offers great promise in the pharmaceutical field, particularly in drug delivery systems. Disulphide bonds, which commonly occur in peptides and proteins and have been used as drug-glutathione conjugates, are reductively cleaved in the colon. The intrinsic stability of a disulphide relative to thiol groups is determined by the redox potential of the environment. The objective of this study was to synthesise a trimesic acid-based disulphide cross-linked polymer that could potentially be used for targeted delivery to the colon. The monomer was synthesised by an amide coupling reaction between trimesic acid and (triphenylmethyl) thioethylamine using a two-step synthesis method. The s-trityl group was removed using a cocktail of trifluoroacetic acid and triethylsilane to expose the thiols in preparation for further polymerisation. The resulting polymers (P10, P15, P21, P25, and P51, generated using different molar ratios) were reduced after 1.5 h of reduction time. Scanning electron microscopy images of the polymers showed spherical, loose, or tight patterns depending on the molar ratio of polymerisation. These polymers also exhibited efficient dissolution under various gastrointestinal conditions. Of the five polymers tested, P10 and P15 appeared to be promising drug delivery vehicles for poorly soluble drugs, due to the hydrophobic nature of the polymers.
  • Publication
    Redox-sensitive linear and cross-linked cystamine- based polymers for colon-targeted drug delivery: Design, synthesis, and characterisation
    ( 2020-05-01)
    Ng Y.M.
    ;
    ;
    Chiu H.I.
    ;
    Lim V.
    Cystamine-based polymers may help to achieve controlled and targeted drug delivery to the colon due to their susceptibility to breakage of the disulfide linkage in the low redox potential environment of the colon. In this study, two linear cystamine-based polymers with similar repeating units (LP1 and LP2) and a cross-linked cystamine-based polymer (BP) were synthesised and their kinetics and the various physical conditions underlying cystamine-based polymerisation were evaluated. In brief, N1, N6-bis(2-(tritylthio)ethyl)adipamide (2) was synthesised from the reaction of triphenylmethanol and cysteamine. Next, the trityl group of 2 was removed with trifluoroacetic acid and triethylsilane before proceeding to oxidative polymerisation of the end product, N1, N6-bis(2- mercaptoethyl)adipamide (3) to LP1. The Schotten-Bauman reaction was applied to synthesise LP2 and BP from the reaction of cystamine with adipoyl chloride or trimesoyl chloride. Scanning electron microscopy, energy-dispersive X-ray spectroscopy, and mapping showed that oxygen, nitrogen, sulfur, and carbon were homogenously distributed in the polymers, with LP2 and BP having less porous morphologies compared to LP1. Results of zinc-acetic acid reduction showed that all polymers began to reduce after 15 min. Moreover, all synthesised polymers resisted stomach and small intestine conditions and only degraded in the presence of bacteria in the colon environment. Thus, these polymers have great potential for drug delivery applications. LP2 and BP, which were synthesised using the Schotten-Bauman reaction, were more promising than LP1 for colon-targeted drug delivery.
  • Publication
    Optimization of biogenic synthesis of silver nanoparticles from flavonoid-rich Clinacanthus nutans leaf and stem aqueous extracts
    ( 2020-07-01) ;
    Che Mood C.N.A.
    ;
    Ahmad N.H.
    ;
    Sandai D.
    ;
    Lee C.K.
    ;
    Lim V.
    Background: Silver nanoparticles (AgNPs) are widely used in food industries, biomedical, dentistry, catalysis, diagnostic biological probes and sensors. The use of plant extract for AgNPs synthesis eliminates the process of maintaining cell culture and the process could be scaled up under a non-aseptic environment. The purpose of this study is to determine the classes of phytochemicals, to biosynthesize and characterize the AgNPs using Clinacanthus nutans leaf and stem extracts. In this study, AgNPs were synthesized from the aqueous extracts of C. nutans leaves and stems through a non-toxic, cost-effective and eco-friendly method. Results: The formation of AgNPs was confirmed by UV-Vis spectroscopy, and the size of AgNP-L (leaf) and AgNP-S (stem) were 114.7 and 129.9 nm, respectively. Transmission electron microscopy (TEM) analysis showed spherical nanoparticles with AgNP-L and AgNP-S ranging from 10 to 300 nm and 10 to 180 nm, with average of 101.18 and 75.38 nm, respectively. The zeta potentials of AgNP-L and AgNP-S were recorded at -42.8 and -43.9 mV. X-ray diffraction analysis matched the face-centred cubic structure of silver and was capped with bioactive compounds. Fourier transform infrared spectrophotometer analysis revealed the presence of few functional groups of phenolic and flavonoid compounds. These functional groups act as reducing agents in AgNPs synthesis. Conclusion: These results showed that the biogenically synthesized nanoparticles reduced silver ions to silver nanoparticles in aqueous condition and the AgNPs formed were stable and less toxic.
  • Publication
    Docetaxel-loaded disulfide cross-linked nanoparticles derived from thiolated sodium alginate for colon cancer drug delivery
    ( 2020-01-01)
    Chiu H.I.
    ;
    Ayub A.D.
    ;
    ;
    Yahaya N.
    ;
    Kadir E.A.
    ;
    Lim V.
    In this study, fluorescein-labelled wheat germ agglutinin (fWGA)-conjugated disulfide cross-linked sodium alginate nanoparticles were developed to specifically target docetaxel (DTX) to colon cancer cells. Different amounts of 3-mercaptopropionic acid (MPA) were covalently attached to sodium alginate to form thiolated sodium alginate (MPA1–5). These polymers were then self-assembled and air-oxidised to form disulfide cross-linked nanoparticles (MP1–5) under sonication. DTX was successfully loaded into the resulting MP1–5 to form DTX-loaded nanoparticles (DMP1– 5). DMP2 had the highest loading efficiency (17.8%), thus was chosen for fWGA surface conjugation to form fWGA-conjugated nanoparticles (fDMP2) with a conjugation efficiency of 14.1%. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analyses showed spherical nanoparticles, and an in vitro drug release study recorded a cumulative drug release of 48.6%. Dynamic light scattering (DLS) analysis revealed a mean diameter (MD) of 289 nm with a polydispersity index (PDI) of 0.3 and a zeta potential of −2.2 mV for fDMP2. HT-29 human colon cancer cells treated with fDMP2 showed lower viability than that of L929 mouse fibroblast cells. These results indicate that fDMP2 was efficiently taken up by HT-29 cells (29.9%). Fluorescence and confocal imaging analyses also showed possible internalisation of nanoparticles by HT-29 cells. In conclusion, fDMP2 shows promise as a DTX carrier for colon cancer drug delivery.