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Voices in Molecular Pharmaceutics: Meet Yan Shan Loo, a Graduate Student Exploring Nanoformulations of Natural Products

Loo YS

Mol Pharm, 2024 Feb 05;21(2):371-372.
PMID: 37867294 DOI: 10.1021/acs.molpharmaceut.3c00927
Fulltext Role of Diet in Colorectal Cancer Incidence: Umbrella Review of Meta-analyses of Prospective Observational Studies

Veettil SK, Wong TY, Loo YS, Playdon MC, Lai NM, Giovannucci EL, et al.

JAMA Netw Open, 2021 02 01;4(2):e2037341.
PMID: 33591366 DOI: 10.1001/jamanetworkopen.2020.37341

Importance: Several meta-analyses have summarized evidence for the association between dietary factors and the incidence of colorectal cancer (CRC). However, to date, there has been little synthesis of the strength, precision, and quality of this evidence in aggregate.
Objective: To grade the evidence from published meta-analyses of prospective observational studies that assessed the association of dietary patterns, specific foods, food groups, beverages (including alcohol), macronutrients, and micronutrients with the incidence of CRC.
Data Sources: MEDLINE, Embase, and the Cochrane Library were searched from database inception to September 2019.
Evidence Review: Only meta-analyses of prospective observational studies with a cohort study design were eligible. Evidence of association was graded according to established criteria as follows: convincing, highly suggestive, suggestive, weak, or not significant.
Results: From 9954 publications, 222 full-text articles (2.2%) were evaluated for eligibility, and 45 meta-analyses (20.3%) that described 109 associations between dietary factors and CRC incidence were selected. Overall, 35 of the 109 associations (32.1%) were nominally statistically significant using random-effects meta-analysis models; 17 associations (15.6%) demonstrated large heterogeneity between studies (I2 > 50%), whereas small-study effects were found for 11 associations (10.1%). Excess significance bias was not detected for any association between diet and CRC. The primary analysis identified 5 (4.6%) convincing, 2 (1.8%) highly suggestive, 10 (9.2%) suggestive, and 18 (16.5%) weak associations between diet and CRC, while there was no evidence for 74 (67.9%) associations. There was convincing evidence of an association of intake of red meat (high vs low) and alcohol (≥4 drinks/d vs 0 or occasional drinks) with the incidence of CRC and an inverse association of higher vs lower intakes of dietary fiber, calcium, and yogurt with CRC risk. The evidence for convincing associations remained robust following sensitivity analyses.
Conclusions and Relevance: This umbrella review found convincing evidence of an association between lower CRC risk and higher intakes of dietary fiber, dietary calcium, and yogurt and lower intakes of alcohol and red meat. More research is needed on specific foods for which evidence remains suggestive, including other dairy products, whole grains, processed meat, and specific dietary patterns.
Fulltext Efficacy and safety of posaconazole for the prevention of invasive fungal infections in immunocompromised patients: a systematic review with meta-analysis and trial sequential analysis

Wong TY, Loo YS, Veettil SK, Wong PS, Divya G, Ching SM, et al.

Sci Rep, 2020 09 03;10(1):14575.
PMID: 32884060 DOI: 10.1038/s41598-020-71571-0

Invasive fungal infections are a potentially life-threatening complication in immunocompromised patients. The aim of this study was to assess the efficacy and safety of posaconazole as compared with other antifungal agents for preventing invasive fungal infections in immunocompromised patients. Embase, CENTRAL, and MEDLINE were searched for randomized conweekmonthtrolled trials (RCTs) up to June 2020. A systematic review with meta-analysis of RCTs was performed using random-effects model. Trial sequential analysis (TSA) was conducted for the primary outcome to assess random errors. A total of five RCTs with 1,617 participants were included. Posaconazole prophylaxis was associated with a significantly lower risk of IFIs (RR, 0.43 [95% CI 0.28 to 0.66, p = 0.0001]) as compared to other antifungal agents. No heterogeneity was identified between studies (I2 = 0%). No significant associations were observed for the secondary outcomes measured, including risk reduction of invasive aspergillosis and candidiasis, clinical failure, all-cause mortality, and treatment-related adverse events, except for infection-related mortality (RR, 0.31 [95% CI 0.15 to 0.64, p = 0.0001]). Subgroup analysis favoured posaconazole over fluconazole for the prevention of IFIs (RR, 0.44 [95% CI 0.28 to 0.70, p = 0.0004]). TSA confirmed the prophylactic benefit of posaconazole against IFIs. Posaconazole is effective in preventing IFIs among immunocompromised patients, particularly those with hematologic malignancies and recipients of allogenic hematopoietic stem cell transplantation.
Biomimetic bacterial and viral-based nanovesicles for drug delivery, theranostics, and vaccine applications

Loo YS, Bose RJ, McCarthy JR, Mat Azmi ID, Madheswaran T

Drug Discov Today, 2021 04;26(4):902-915.
PMID: 33383213 DOI: 10.1016/j.drudis.2020.12.017

Smart nanocarriers obtained from bacteria and viruses offer excellent biomimetic properties which has led to significant research into the creation of advanced biomimetic materials. Their versatile biomimicry has application as biosensors, biomedical scaffolds, immobilization, diagnostics, and targeted or personalized treatments. The inherent natural traits of biomimetic and bioinspired bacteria- and virus-derived nanovesicles show potential for their use in clinical vaccines and novel therapeutic drug delivery systems. The past few decades have seen significant progress in the bioengineering of bacteria and viruses to manipulate and enhance their therapeutic benefits. From a pharmaceutical perspective, biomimetics enable the safe integration of naturally occurring bacteria and virus particles to achieve high, stable rates of cellular transfection/infection and prolonged circulation times. In addition, biomimetic technologies can overcome safety concerns associated with live-attenuated and inactivated whole bacteria or viruses. In this review, we provide an update on the utilization of bacterial and viral particles as drug delivery systems, theranostic carriers, and vaccine/immunomodulation modalities.
Coencapsulation of Gemcitabine and Thymoquinone in Citrem-Phosphatidylcholine Hexosome Nanocarriers Improves In Vitro Cellular Uptake in Breast Cancer Cells

Loo YS, Zahid NI, Madheswaran T, Ikeno S, Nurdin A, Mat Azmi ID

Mol Pharm, 2023 Sep 04;20(9):4611-4628.
PMID: 37587099 DOI: 10.1021/acs.molpharmaceut.3c00333

Lyotropic liquid crystalline nanoassemblies (LLCNs) are internally self-assembled (ISA)-somes formed by amphiphilic molecules in a mixture comprising a lipid, stabilizer, and/or surfactant and aqueous media/dispersant. LLCNs are unique nanoassemblies with versatile applications in a wide range of biomedical functions. However, they comprise a nanosystem that is yet to be fully explored for targeted systemic treatment of breast cancer. In this study, LLCNs proposed for gemcitabine and thymoquinone (Gem-TQ) co-delivery were prepared from soy phosphatidylcholine (SPC), phytantriol (PHYT), or glycerol monostearate (MYVR) in optimized ratios containing a component of citric and fatty acid ester-based emulsifier (Grinsted citrem) or a triblock copolymer, Pluronic F127 (F127). Hydrodynamic particle sizes determined were below 400 nm (ranged between 96 and 365 nm), and the series of nanoformulations displayed negative surface charge. Nonlamellar phases identified by small-angle X-ray scattering (SAXS) profiles comprise the hexagonal, cubic, and micellar phases. In addition, high entrapment efficiency that accounted for 98.3 ± 0.1% of Gem and 99.5 ± 0.1% of TQ encapsulated was demonstrated by the coloaded nanocarrier system, SPC/citrem/Gem-TQ hexosomes. Low cytotoxicity of SPC-citrem hexosomes was demonstrated in MCF10A cells consistent with hemo- and biocompatibility observed in zebrafish (Danio rerio) embryos for up to 96 h postfertilization (hpf). SPC/citrem/Gem-TQ hexosomes demonstrated IC50 of 24.7 ± 4.2 μM in MCF7 breast cancer cells following a 24 h treatment period with the moderately synergistic interaction between Gem and TQ retained (CI = 0.84). Taken together, biocompatible SPC/citrem/Gem-TQ hexosomes can be further developed as a multifunctional therapeutic nanodelivery approach, plausible for targeting breast cancer cells by incorporation of targeting ligands.
Medicinal benefits, biological, and nanoencapsulation functions of riboflavin with its toxicity profile: A narrative review

Lee TY, Farah N, Chin VK, Lim CW, Chong PP, Basir R, et al.

Nutr Res, 2023 Nov;119:1-20.
PMID: 37708600 DOI: 10.1016/j.nutres.2023.08.010

Riboflavin is a precursor of the essential coenzymes flavin mononucleotide and flavin adenine dinucleotide. Both possess antioxidant properties and are involved in oxidation-reduction reactions, which have a significant impact on energy metabolism. Also, the coenzymes participate in metabolism of pyridoxine, niacin, folate, and iron. Humans must obtain riboflavin through their daily diet because of the lack of programmed enzymatic machineries for de novo riboflavin synthesis. Because of its physiological nature and fast elimination from the human body when in excess, riboflavin consumed is unlikely to induce any negative effects or develop toxicity in humans. The use of riboflavin in pharmaceutical and clinical contexts has been previously explored, including for preventing and treating oxidative stress and reperfusion oxidative damage, creating synergistic compounds to mitigate colorectal cancer, modulating blood pressure, improving diabetes mellitus comorbidities, as well as neuroprotective agents and potent photosensitizer in killing bloodborne pathogens. Thus, the goal of this review is to provide a comprehensive understanding of riboflavin's biological applications in medicine, key considerations of riboflavin safety and toxicity, and a brief overview on the nanoencapsulation of riboflavin for various functions including the treatment of a range of diseases, photodynamic therapy, and cellular imaging.
Fulltext Recent Advances in the Development of Liquid Crystalline Nanoparticles as Drug Delivery Systems

Leu JSL, Teoh JJX, Ling ALQ, Chong J, Loo YS, Mat Azmi ID, et al.

Pharmaceutics, 2023 May 06;15(5).
PMID: 37242663 DOI: 10.3390/pharmaceutics15051421

Due to their distinctive structural features, lyotropic nonlamellar liquid crystalline nanoparticles (LCNPs), such as cubosomes and hexosomes, are considered effective drug delivery systems. Cubosomes have a lipid bilayer that makes a membrane lattice with two water channels that are intertwined. Hexosomes are inverse hexagonal phases made of an infinite number of hexagonal lattices that are tightly connected with water channels. These nanostructures are often stabilized by surfactants. The structure's membrane has a much larger surface area than that of other lipid nanoparticles, which makes it possible to load therapeutic molecules. In addition, the composition of mesophases can be modified by pore diameters, thus influencing drug release. Much research has been conducted in recent years to improve their preparation and characterization, as well as to control drug release and improve the efficacy of loaded bioactive chemicals. This article reviews current advances in LCNP technology that permit their application, as well as design ideas for revolutionary biomedical applications. Furthermore, we have provided a summary of the application of LCNPs based on the administration routes, including the pharmacokinetic modulation property.
Fulltext Effects of qigong on systolic and diastolic blood pressure lowering: a systematic review with meta-analysis and trial sequential analysis

Ching SM, Mokshashri NR, Kannan MM, Lee KW, Sallahuddin NA, Ng JX, et al.

BMC Complement Med Ther, 2021 Jan 06;21(1):8.
PMID: 33407414 DOI: 10.1186/s12906-020-03172-3

BACKGROUND: The benefits of qigong for systolic and diastolic blood pressure (BP) reduction have been noted in previously published systematic reviews; however, the data on its effectiveness has been at best scarce. We aimed to update the evidence of qigong on blood pressure reduction after taking into consideration the risks of random error and reliability of data in the cumulative meta-analysis using trial sequential analysis (TSA).
METHODS: Included trials were assessed using Cochrane risk of bias instrument. We performed meta-analysis with random-effects model and random errors were evaluated with TSA. We performed the search for the eligible randomized controlled trial (RCT) through Medline, Cinahl, Cochrane Central Register of Controlled Trials and also PubMed.
RESULTS: A total of 370 subjects sourced from seven eligible RCTs were entered into the analysis. The pooled results demonstrated the significant reduction with the use of qigong of the systolic blood pressure [weighted mean difference (WMD), - 10.66 mmHg (95% confidence interval (CI) = - 17.69,-3.62, p