Tocotrienols (T3), a subfamily of vitamin E, are gaining recognition for their potent antioxidant, anti-inflammatory, and neuroprotective properties. However, their use in functional foods and medicinal products faces challenges such as low water solubility, instability under environmental conditions, and susceptibility to oxidative degradation. This study aims to address these challenges by using spray drying as an encapsulation technique to convert liquid nano emulsions of T3 into stable, dry powders. The process is guided by the Quality by Design (QbD) methodology, which optimises the spray drying parameters and the selection of wall materials to enhance the stability of nano-T3 powders. The results indicate that the combination of sodium caseinate and fibersol as wall materials effectively encapsulated T3, preserving its chemical integrity during processing. The optimised spray drying conditions produced nano-sized particles with ideal characteristics such as excellent flowability (10.71 ± 1.12%), wettability (93.07 ± 6.01%), low moisture content (1.79 ± 0.02%), particle size (100.42 ± 48.05 nm) and Vitamin E content (579.00 ± 233.39 mg/g). However, stability testing revealed that while the nano-T3 powder retained its chemical stability, moisture absorption over time led to particle aggregation and a decrease in T3 content. This indicates a need for further optimisation to improve moisture resistance and long-term stability. The study highlights the significant impact of wall materials and spray-drying parameters on the properties of nano-T3 powders and provides valuable insights into enhancing their stability and efficacy. Future research should focus on refining the encapsulation matrix and exploring the incorporation of antioxidants to mitigate degradation, thereby improving the stability and functional applications of nano-T3 in pharmaceuticals, nutraceuticals, and functional foods. In conclusion, this study demonstrates the potential of spray-dried nano-T3 as a stable, bioactive ingredient for diverse applications, with room for improvement in moisture resistance to enhance long-term stability.

The emergence and re-emergence of viral pathogens such as SARS-CoV-2, human immunodeficiency virus (HIV-1), hepatitis C virus (HCV), Zika virus (ZIKV), and dengue virus (DENV) continue to pose significant global health challenges. Viral proteases play a central role in viral replication through polyprotein processing and therefore represent attractive targets for antiviral drug development. This dissertation investigates the identification of synthetic viral protease inhibitors using an integrated in silico approach comprising Structure-Based Pharmacophore Modelling (SBPM), virtual screening, molecular docking, and pharmacokinetic prediction. High-resolution crystal structures of five disease-specific viral proteases (PDB IDs: 8HUR, 4WF8, 3SPK, 2FOM, and 5H4I) were analyzed to generate validated structure-based pharmacophore models using the Pharmit platform. These models were applied to virtually screen large compound libraries, including ZINC and MolPort, to identify molecules exhibiting key interaction features within protease active sites. The top-ranked virtual hits were further evaluated through molecular docking simulations using iGEMDOCK to predict binding conformations, interaction profiles, and relative binding affinities. Drug-likeness and ADMET properties were assessed using the SwissADME web tool. Several chemically diverse lead scaffolds, including triazine, indazole, and isoquinoline cores, demonstrated favorable hydrogen bonding, π–π stacking, and hydrophobic interactions with conserved catalytic residues across multiple viral proteases. Notably, some compounds exhibited multi-target binding potential, indicating suitability for broad-spectrum antiviral development. Overall, this study demonstrates that SBPM integrated with molecular docking provides an efficient and cost-effective computational framework for antiviral lead identification and establishes a strong foundation for future experimental validation and optimization. Keywords: viral proteases; structure-based drug design; pharmacophore modelling; virtual screening

Emerging evidence of meta-analyses suggested that periodontal disease (PD) mediated by oral bacteria may increase the risk of developing neurodegenerative disorders. However, the findings were inconsistent and inconclusive. An umbrella review makes it feasible to summarise the current evidence from the published meta-analyses on this topic and enable the ranking of evidence. In addition, among periodontal pathogens, Porphyromonas gingivalis produces a calcium-independent peptidylarginine deiminase enzyme (PPAD) that induces hypercitrullination, a process that has been proposed to contribute to the onset of neurodegenerative disorders. Nonetheless, PPAD inhibitors have been scarcely reported in the literature, highlighting a significant gap in the current body of research. Therefore, this study aimed to (i) conduct an umbrella review to summarise the associations between oral bacterial diseases and neurodegenerative disorders and assess the credibility of evidence supporting such associations and (ii) evaluate the binding interactions and identify potential inhibitors of PPAD through molecular docking simulations, using the 15 compounds previously identified via 2D ligand-based similarity screening. An umbrella review of 6 eligible meta-analyses including 17 associations was conducted using predefined eligibility criteria and the credibility of evidence was graded according to AMSTAR-2 methodological quality assessment. In parallel, molecular docking simulations were performed to examine binding affinity and key residue interactions of 15 compounds within the PPAD binding site. Nine of 17 associations (52.9 %) showed statistical significance at P ≤ 0.05 based on random-effects models between PD and neurodegenerative disorders. Twelve out of the 17 associations (70.6%) had considerable heterogeneity (I2 > 50%), suggesting that the pooled estimates should be interpreted carefully. Only one association from 17 associations showed a small-study effect. Docking analyses revealed that several compounds exhibited favourable binding affinity within the PPAD binding site interacting with essential residues, particularly (4S)-5-[[(2S)-1-[[(2S)-1-Amino-3-[4-[difluoro(phosphono)methyl]phenyl]-1-oxopropan-2-yl]amino]-3-[4-[difluoro(phosphono)methyl]phenyl]-1-oxopropan-2-yl]amino]-4-benzamido-5-oxopentanoic acid exhibiting binding score of -9.737 kcal/mol. Notably, N-acetyl-L-arginine was estimated to interact directly with His236 of the catalytic triad, suggesting potential inhibition. Collectively, the umbrella review and molecular docking simulations support a biological plausible, though not definitive, link between PD and neurodegenerative disorders. Further longitudinal studies and experimental enzymatic and cellular evaluations are necessary to enhance PPAD-target inhibitor development toward clinical application.

Colorectal Cancer (CRC) is among the foremost causes of cancer-related mortality in Malaysia and worldwide. This warrants the continuous development of novel, efficient and safe therapeutic options. Glucomoringin (GMG) is a secondary metabolite derived from the plant, Moringa oleifera Lam, which is highly known for its nutritional, medicinal and environmental benefits. Preclinical studies have identified promising anticancer properties from extracts of M. oleifera and the associated secondary metabolites. Hence, this study aims to investigate the anticancer potential activity of GMG against human colorectal cancer cell lines (HCT116, HT29, HCC2998 and SW48). The cytotoxic effects of GMG were evaluated through cell viability using the MTT assay at incubation time periods of 24, 48 and 72 hours, with doxorubicin as the standard chemotherapeutic drug. Changes in nuclear morphology and apoptotic features were also assessed through Hoechst 33342 staining and fluorescence microscopy following treatment with GMG. It was observed that GMG manifests a dose-and time-dependent cytotoxicity across all colorectal cancer cell lines, with HCC2998 and SW48 showing the most significant reduction in cell viability, post treatment. GMG-treated cells displayed intensified nuclear fluorescence and irregularity in nuclear morphology, which is consistent with apoptotic cell death features. However, despite reports indicating GMG as a potent anticancer agent, our findings shows that GMG has limited antiproliferative effects, even with an IC50 value of more than 100 μM and prolonged exposure of 72 hours. Additionally, its anticancer activity is also markedly lower compared to that of the standard chemotherapy drug, suggesting limited therapeutic potential in its natural form. Nonetheless, these observations provide significant insights into the limitations of GMG and highlight important future research directions aimed at enhancing and unlocking its therapeutic potential.

Epstein-Barr virus (EBV) is a class I carcinogen human herpes virus which has infected 90% of humanity and most prevalent among Asians, especially Chinese. After primary infection, EBV establishes the lifelong virus carrier state. EBV can be detected in two different tissues namely, B lymphocytes and epithelial cells. EBV is linked to the pathogenesis of a variety of human tumors and disorders, such as Burkitt’s lymphoma, and nasopharyngeal carcinoma. Algae are a potential source of antiviral compounds; however, there have been very few reports on the antiviral activity of microalgae extracts against EBV. The objective of this study was to investigate the antiviral activity of extracts from three microalgae, namely Ankistrodesmus convolutus UMACC 101, Synechococcus elongatus UMACC 105 and Spirulina platensis UMACC 161 against EBV in Burkitt’s lymphoma (BL) cell lines. Three EBV-positive BL cell lines, namely Akata, B95-8 and P3HR-1 were used as in vitro study model. A bioassay-guided fractionation approach was used for the screening of antiviral activity. The antiviral activity of the microalgae extracts was elucidated based on their inhibition efficacy in reducing number of cell-free viral particles being released by chemically induced lytic BL cells. This was assessed by quantifying the cell-free DNA using real-time PCR technique. In addition, the inhibition activity of microalgae extracts against the expression of the viral proteins LMP1, EBNA1 and ZEBRA in BL cells was assessed using immunocytochemistry technique. Two antiviral drugs namely acyclovir and foscarnet were chosen as positive controls. Methanol extracts from Ankistrodesmus convolutus and Synechococcus elongatus displayed low cytotoxicity (IC50 >200 µg/mL) and reduced the cell-free EBV viral load most effectively (EC50 <0.01 µg/mL) and thus, displayed high therapeutic index (>28000). The extracts decreased the expression of EBNA1 (>45%), LMP1 (>38%) and ZEBRA (>67%) effectively in P3HR-1 cells. After column chromatography fractionation, the non-polar fraction of the extract from Synechococcus elongatus (SEF1) reduced the amount of cell-free EBV DNA most effectively (EC50= 2.9μg/mL; therapeutic index >69) with low cytotoxicity (IC50 >200 μg/mL). SEF1 inhibited the expression of EBNA1 and ZEBRA (>40%) effectively in P3HR-1 cells. When SEF1 was further fractionated using HPLC, the sub-fraction SEF1’a was most active in reducing the cell-free EBV DNA (EC50= 1.38µ/mL; therapeutic index >14.5). It inhibited the expression of LMP1 moderately (25%) in P3HR-1 cells. The microalgae extracts did not interact with the cytoskeleton components (actin and tubulin) of BL cells during the release of cell-free EBV particles as revealed by the immunofluorescence study. The active constituents in the microalgae extracts tested might consist of pigments such as chlorophylls, carotenoids, phaeophytins and phycobilins. In conclusion, methanol extracts from Ankistrodesmus convolutus, Synechococcus elongatus and Spirulina platensis showed antiviral activity by inhibiting the release of EBV from the BL cells and the expression of the viral proteins LMP1, EBNA1 and ZEBRA in the host cells. The potential of the microalgae as a source of antiviral drugs against EBV is worth exploring.

Introduction: Currently there is an uptrend in the provision of Extended Pharmacy Services (EPS) among community pharmacists (CPs). EPS referred to various services that beyond the traditional pharmacists’ roles of dispensing medicines such as public health educational program, clinical services and medicine use review. However, such services were only reported in other developed countries but not in Malaysia. Within this context, the present study aimed to explore the types of EPS available, CPs’ perceptions and attitudes towards the provision of EPS. This study also identified the perceived barriers and facilitators towards the provision of EPS. Methods: A descriptive cross-sectional study was conducted. A total of 236 samples were collected through convenience sampling around Selangor and Kuala Lumpur region. The questionnaire consisted of 6 domains including demographic profile, the type of EPS, pharmacist’s perception, perceived barriers, perceived facilitator and pharmacist attitude towards the provision of EPS. All questions were scored using five-point Likert Scale. All the data were analysis through SPSS using descriptive statistics analysis, Mann-Whitney and Kruskal Wallis test. Results: CPs are willing to provide EPS in near future. For the time being, health screening test were the most performed EPS. CPs often/always performed blood pressure test, (97.8%), glucose test (96.6%) and cholesterol test (83.0%). Besides that, the often/always performed counselling sessions for cough and cold (95.8%) and nutritional supplement (94.5%). However, other advanced services like smoking cessation and weight management services were not frequently performed. The top 5 perceived barriers identified includes the lack of standardized practice model for EPS (87.3%), high pressure on generating sales (86.4%), lack of patient awareness (84.4%), 4 lack of access to patient medical record (83.5%) and shortage of time (80.5%). Whereas the support and encouragement from government and other pharmacy organization were identified as the most prominent facilitator towards the implementation of EPS. Conclusion: CPs showed a positive attitude towards the provision of EPS. For the time being, there are various EPS that had already been developed and implemented. However, the identified barriers should be intervened, and facilitators should be executed to implement EPS successfully in near future. Keywords: Pharmaceutical Care Services, Extended Pharmacy Services, Expanded Pharmacy Services, Enhanced Pharmacy Services, Barriers, Facilitators, Community Pharmacy

Dietary fat when consumed reduces hunger and impairs food intake by eliciting satiety signals and these signals are evoked by entry of triacylglycerol after hydrolization to fatty acids into the small intestine. 1,3-dipalmitoyl-2-oleoyglycerol (POP-), 1,3-distearoyl-2-oleoylglycerol (SOS-) and 1,2,3-triolein (OOO-) type of fats have different melting characteristics that may affect postprandial blood lipids, gut hormone concentrations, insulinemic response and selected cardiovascular disease markers in human volunteers. The main objective of this study is to compare the effects of edible fats with either palmitic acid (16:0) (palm mid-fraction) or stearic acid (18:0) (shea stearin) predominantly at the sn-1 and sn-3 positions on postprandial lipemia and gut hormone concentrations. A randomized, double-blind crossover (3 × 3 arms) orthogonal Latin-square design was used on 36 healthy adults (18 males, 18 females; mean age = 23 years). Each subject received 3 different test muffins (each containing 53 g of test fat) in random order separated by 2 weeks over a 6-week period. The test fats of different melting points were palm mid- fraction (PMF; POP-rich), shea stearin (SS; SOS-rich) and high- oleic sunflower oil (HOSF; OOO-rich) During a postprandial test, each subject was provided with a test muffin plus milkshake (total 3.67 MJ or 876 kcal) in the morning and blood samples were collected at half-hourly intervals until 4.0 hours. No significant difference (p>0.05) was observed between the 3 test meals for postprandial responses in plasma TC, Lp(a), apo(B), NEFA, GLP-1, PYY, ghrelin, VAS, PAI-1, IL-6, TNF-α, glucose, insulin and satiety (VAS scores). Plasma TAG peaked at about 4 hours; levels in the PMF- and HOSF- subjects were significantly higher (p<0.05) compared with SS-subjects after 90 minutes. PMF and HOSF exerted a higher postprandial GIP response (p<0.05) as compared to SS. Plasma C-peptide levels, as a measure of insulinemic response, rose sharply 5.5- folds in all groups, peaking after 90 minutes; levels in the SS group declined at a faster rate (p<0.05) than in the PMF- and HOSF- groups. The POP- and OOO- fats induced similar effects on all the biochemical/physiological outcome measures investigated. In contrast, the SOS- type fat (shea stearin) induced a slower rise (p<0.05) in postprandial TAG and GIP levels and a faster return of plasma C-peptide levels to baseline.

Multidrug resistance (MDR) is a serious problem that causes failure in chemotherapy. P-glycoprotein (P-gp) is widely distributed in the intestine, liver and kidneys contributing as one of the major mechanism that causes efflux of chemotherapeutic agents, resulting in ineffective therapeutic level during treatment. However, recent advances in drug delivery systems have made it possible to circumvent MDR issues. In this study, an attempt was made to develop Poly-lactide co-glycolide (PLGA) nanoparticles for oral chemotherapy by co encapsulating doxorubicin (Dox) as the chemotherapeutic agent and cyclosporine-A (CysA) as the chemosensitizer that will function to inhibit P-gp to increase uptake of Dox. High Performance Liquid Chromatography (HPLC) methods were developed and validated for detection and quantification of Dox and CysA. Optimized Dox-CysA nanoparticles were reported to be in 214±4.56 nm of size, zeta potential of -30.1±9.42 and polydispersity index of 0.139±0.09.Transmission Electron Microscopy (TEM) image shows spherical nanoparticles. Differential Scanning Calorimetry (DSC) thermogram indicates Dox and CysA exist in amorphous form in PLGA nanoparticles. Dox and CysA nanoparticles were formulated separately alongside optimized nanoparticle for comparison purposes in drug release and cytotoxicity studies. Dox released slowest from Dox-CysA nanoparticles whilst CysA from CysA nanoparticles in Phosphate Buffer Saline (PBS), promising a controlled release. Cytotoxicity studies conducted on Caco 2 cell line, showed the lowest cell viability of 34%, for Dox-CysA loaded nanoparticles and 76.8% for Dox loaded nanoparticles while a combination of Dox loaded nanoparticles and CysA loaded nanoparticles at the same concentration gave a cell viability of 47.1%, with all treatment containing Dox at 0.71μg/ml. Co-administration of CysA together with Dox in the same nanoparticles formulation proves to increase the uptake of Dox in vitro.