Siti Nur Aishah Mat Yusuf

Disulphide-containing polymers have recently been recognized as an invaluable material in delivering chemotherapeutic drug. Disulphide-based polymers are considered potential candidates because of their sensitivity to redox conditions and their stability in the challenging environment of the upper GI tract. In this study, three polymers have been successfully synthesised via oxidation of citric acid derivative-thiolated monomer and dithiol monomers. Three disulphide-based polymers were successfully synthesized and used to encapsulate docetaxel and salinomycin, demonstrating their applicability for colon-targeted drug delivery.

Mariposa Christia vespertilionis (MCV) is also known as butterfly wing plant, or commonly known as ‘pokok rerama’ in Malaysia. This plant belongs to the Fabaceae family. Its bioactive compounds including triterpenes, alkaloids, fatty acids, phenol, alkanes and alcohol have shown antioxidant activity. The objective of this study is to synthesis silver nanoparticles together with MCV leaves extract using ultrasonic-assisted extraction (UAE) as an extraction method and to evaluate its antioxidative activity. The best conditions (concentration of silver nitrate and incubation temperature) for formation of AgNPs were visualised by UV-Vis spectroscopy. The absorbance peaks for both conditions were 450 nm and 430 nm respectively. Both MCV extract and synthesized nanoparticles have been characterized by Fourier-transform infrared spectroscopy (FTIR) to determine the functional group that responsible in reduction of silver ions. The AgNPs was also characterized by using Transmission Electron Microscopy (TEM) to determine the morphology and size of the synthesised silver nanoparticles (30 to 50 nm). Total phenolic content and total flavonoids content were also conducted for MCV extracts thus the value achieved was 0.429 ± 0.046 mg GAE/g and 0.033 ± 0.033 mg QU/g. Antioxidant activity was done by using DPPH solution. The scavenging activity for MCV extract was higher compared to the synthesised AgNPs. As conclusion, MCV leaves has potential as antioxidant agent which may be beneficial in preventing degenerative diseases.

Mariposa Christia vespertilionis (MCV) has gained attention in cancer medicine development. Nowadays, plant-based nanoparticles have been widely used in drug delivery as they bring minimal effects to healthy cells and exhibiting antiproliferative effects to cancer cells. This study was conducted to investigate the antiproliferative properties of synthesised silver nanoparticles (AgNPs) using MCV aqueous leaf extract on HT29 cell line. The qualitative phytochemical analysis has proved that flavonoids, alkaloids, glycosides and tannins were present in MCV. Based on the ultraviolet-visible (UV-vis) spectrometry spectrum, the optimum conditions to synthesise highest amount of AgNPs were 15% v/v of extract concentration and 24 h of incubation period. The synthesised AgNPs were characterised by Fourier-transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM) analysis. Flavonoids, alkaloids, glycosides and tannins were responsible in AgNPs formation based on FTIR analysis. In TEM analysis, the obtained nanoparticles were well-distributed with spherical shape. The particle size was in the range from 30 nm to 50 nm. From dimethylthiazol-diphenyltetrazolium bromide (MTT) assay, the synthesised AgNPs was proven to have ability in killing cancer cells (IC50: <12.5 µg/ml). They showed higher killing effect compared to the extract alone but lower than chemotherapy drug 5-fluorouracil (5FU). In conclusion, this study proved that MCV and synthesised AgNPs have the ability to kill cancer cells.

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.

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.

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.

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.

Endogenous and exogenous antioxidants are used to neutralise free radicals and protect the body from free radicals by maintaining the redox balance. The antioxidant properties of Dracaena sanderiana leaves were evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and the total phenolic and flavonoid contents were measured. The classes of secondary metabolites were evaluated through pharmacognostic studies, and active compounds were identified by gas chromatography mass-spectrometry (GC-MS). All ethanol-water extracts and D. sanderiana leaf powder were positive for tannins, saponins, terpenoids, cardiac glycosides, and quinones. Flavonoids were present in 100%, 80%, 60%, and 40% ethanol extracts (E100, E80, E60, and E40). E100 showed the highest total flavonoid content, whereas E60 extract showed the highest antioxidant activity and total phenolic content. GC-MS revealed the presence of glycerol, 2,3-dihydro-3,5-dihydroxy-6-methyl-(4H)-pyran-4-one, n-dodecanoic acid, tetradecanoid acid, (n-) hexadecanoid acid, and n-octadecanoic acid in the E60 extract.