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Fulltext Potential of Endophytic Diaporthe sp. as a New Source of Bioactive Compounds

Nagarajan K, Tong WY, Leong CR, Tan WN

J Microbiol Biotechnol, 2021 Apr 28;31(4):493-500.
PMID: 32627761 DOI: 10.4014/jmb.2005.05012

Endophytic fungi are symbiotically related to plants and spend most of their life cycle within them. In nature, they have a crucial role in plant micro-ecosystem. They are harnessed for their bioactive compounds to counter human health problems and diseases. Endophytic Diaporthe sp. is a widely distributed fungal genus that has garnered much interest within the scientific community. A substantial number of secondary metabolites have been detected from Diaporthe sp. inhabited in various plants. As such, this minireview highlights the potential of Diaporthe sp. as a rich source of bioactive compounds by emphasizing on their diverse chemical entities and potent biological properties. The bioactive compounds produced are of significant importance to act as new lead compounds for drug discovery and development.
Fulltext Potential Antimicrobial Applications of Chitosan Nanoparticles (ChNP)

Rozman NAS, Tong WY, Leong CR, Tan WN, Hasanolbasori MA, Abdullah SZ

J Microbiol Biotechnol, 2019 Jul 28;29(7):1009-1013.
PMID: 31288302 DOI: 10.4014/jmb.1904.04065

Polymeric nanoparticles are widely used for drug delivery due to their biodegradability property. Among the wide array of polymers, chitosan has received growing interest among researchers. It was widely used as a vehicle in polymeric nanoparticles for drug targeting. This review explored the current research on the antimicrobial activity of chitosan nanoparticles (ChNP) and the impact on the clinical applications. The antimicrobial activities of ChNP were widely reported against bacteria, fungi, yeasts and algae, in both in vivo and in vitro studies. For pharmaceutical applications, ChNP were used as antimicrobial coating for promoting wound healing, preventing infections and combating the rise of infectious disease. Besides, ChNP also exhibited significant inhibitory on foodborne microorganisms, particularly on fruits and vegetables. It is noteworthy that ChNP can be also applied to deliver antimicrobial drugs, which further enhance the efficiency and stability of the antimicrobial agent. The present review addresses the potential antimicrobial applications of ChNP from these few aspects.
Cholic acid: a novel steroidal uncompetitive inhibitor against β-lactamase produced by multidrug-resistant isolates

Rashid SA, Norman N, Teo SH, Tong WY, Leong CR, Tan WN, et al.

World J Microbiol Biotechnol, 2021 Aug 16;37(9):152.
PMID: 34398332 DOI: 10.1007/s11274-021-03118-y

β-lactam antibiotics are the most frequently prescribed class of drugs worldwide, due to its efficacy and good safety profile. However, the emergence of β-lactamase producing bacterial strains eliminated the use of β-lactam antibiotics as a chemotherapeutic choice. To restore their usability, a non-antibiotic adjuvant in conjunction with β-lactam antibiotics is now being utilised. Cholic acid potentially acts as an adjuvant since it can blunt the pro-inflammatory activity in human. Our main objective is to scrutinise the inhibition of β-lactamase-producing bacteria by adjuvant cholic acid, synergism of the test drugs and the primary mechanism of enzymatic reaction. Antibacterial effect of the cholic acid-ampicillin (CA-AMP) on 7 β-lactamase positive isolates were evaluated accordingly to disc diffusion assay, antibiotic susceptibility test, as well as checkerboard analysis. Then, all activities were compared with ampicillin alone, penicillin alone, cholic acid alone and cholic acid-penicillin combination. The CA-AMP displayed notable antibiotic activity on all test bacteria and depicted synergistic influence by representing low fractional inhibitory concentration index (FIC ≤ 0.5). According to kinetic analyses, CA-AMP behaved as an uncompetitive inhibitor against beta lactamase, with reducing values of Michaelis constant (Km) and maximal velocity (Vmax) recorded. The inhibitor constant (Ki) of CA-AMP was equal to 4.98 ± 0.3 µM, which slightly lower than ampicillin (5.00 ± 0.1 µM).
The achievement of ligand-functionalized organic/polymeric nanoparticles for treating multidrug resistant cancer

Lee WH, Loo CY, Leong CR, Young PM, Traini D, Rohanizadeh R

Expert Opin Drug Deliv, 2017 08;14(8):937-957.
PMID: 27759437 DOI: 10.1080/17425247.2017.1247804

INTRODUCTION: The effectiveness of conventional cancer chemotherapy is hampered by the occurrence of multidrug resistance (MDR) in tumor cells. Although many studies have reported the development of novel MDR chemotherapeutic agents, clinical success is lacking owing to the high associated toxicity. Nanoparticle-based delivery of chemotherapeutic drugs has emerged as alternative approach to treat MDR cancers via exploitation of leaky vasculature in the tumor microenvironment. Accordingly, functionalization of nanoparticles with target specific ligands can be employed to achieve significant improvements in the treatment of MDR cancer. Areas covered: This review focuses on the recent advances in the functionalization of nanocarriers with specific ligands, including antibodies, transferrin, folate, and peptides to overcome MDR cancer. The limitations of effective ligand-functionalized nanoparticles as well as therapeutic successes in ligand targeting are covered in the review. Expert opinion: Targeting MDR tumors with ligand-functionalized nanoparticles is a promising approach to improve the treatment of cancer. With this approach, higher drug concentrations at targeted sites would be achieved with lower dosage frequencies and reduced side effects in comparison to existing formulations of chemotherapeutic drugs. However, potential toxicities and immunological responses to ligands should be carefully reviewed for viable options in for future MDR cancer treatment.
Fulltext Endophytic Diaporthe sp. ED2 Produces a Novel Anti-Candidal Ketone Derivative

Tong WY, Leong CR, Tan WN, Khairuddean M, Zakaria L, Ibrahim D

J Microbiol Biotechnol, 2017 Jun 28;27(6):1065-1070.
PMID: 28297749 DOI: 10.4014/jmb.1612.12009

This study aimed to examine the anti-candidal efficacy of a novel ketone derivative isolated from Diaporthe sp. ED2, an endophytic fungus residing in medicinal herb Orthosiphon stamieus Benth. The ethyl acetate extract of the fungal culture was separated by open column and reverse phase high-performance liquid chromatography (HPLC). The eluent at retention time 5.64 min in the HPLC system was the only compound that exhibited anti-candidal activity on Kirby-Bauer assay. The structure of the compound was also elucidated by nuclear magnetic resonance and spectroscopy techniques. The purified anti-candidal compound was obtainedas a colorless solid and characterized as 3-hydroxy-5-methoxyhex-5-ene-2,4-dione. On broth microdilution assay, the compound also exhibited fungicidal activity on a clinical strain of Candida albicans at a minimal inhibitory concentration of 3.1 μg/ml. The killing kinetic analysis also revealed that the compound was fungicidal against C. albicans in a concentration- and time-dependent manner. The compound was heat-stable up to 70°C, but its anti-candidal activity was affected at pH 2.
The potential to treat lung cancer via inhalation of repurposed drugs

Lee WH, Loo CY, Ghadiri M, Leong CR, Young PM, Traini D

Adv Drug Deliv Rev, 2018 08;133:107-130.
PMID: 30189271 DOI: 10.1016/j.addr.2018.08.012

Lung cancer is a highly invasive and prevalent disease with ineffective first-line treatment and remains the leading cause of cancer death in men and women. Despite the improvements in diagnosis and therapy, the prognosis and outcome of lung cancer patients is still poor. This could be associated with the lack of effective first-line oncology drugs, formation of resistant tumors and non-optimal administration route. Therefore, the repurposing of existing drugs currently used for different indications and the introduction of a different method of drug administration could be investigated as an alternative to improve lung cancer therapy. This review describes the rationale and development of repositioning of drugs for lung cancer treatment with emphasis on inhalation. The review includes the current progress of repurposing non-cancer drugs, as well as current chemotherapeutics for lung malignancies via inhalation. Several potential non-cancer drugs such as statins, itraconazole and clarithromycin, that have demonstrated preclinical anti-cancer activity, are also presented. Furthermore, the potential challenges and limitations that might hamper the clinical translation of repurposed oncology drugs are described.
Gelatine Film Incorporated with Clitoria ternatea-Derived Anthocyanin Microcapsules, A Food Packaging Material Effective Against Foodborne Pathogens

Leong CR, Daud NS, Tong WY, Cheng SY, Tan WN, Hamin NS, et al.

Food Technol Biotechnol, 2021 Dec;59(4):422-431.
PMID: 35136367 DOI: 10.17113/ftb.59.04.21.7069

Research background: Microbial contamination of food products is one of the significant causes of food spoilage and foodborne illnesses. The use of active packaging films incorporated with antimicrobial agents can be a measure to improve food quality and extend shelf life. Nevertheless, antimicrobial agents such as silver, copper, titanium and zinc in the packaging films have raised concerns among consumers due to toxicity issues.
Experimental approach: The current study aims to develop biodegradable gelatine-based edible films incorporated with microcapsules of Clitoria ternatea-derived anthocyanins as a natural antimicrobial agent. The impact of incorporation of microcapsules with anthocyanins on the morphology, thermal, mechanical, water vapour barrier and physicochemical properties of the gelatine films was evaluated in this study. The effectiveness of the developed films against foodborne pathogens and their application for perishable food protection were also investigated.
Results and conclusions: The results show that incorporating anthocyanin microcapsules enhances the gelatine film physical and mechanical properties by increasing the thickness, tensile strength, Young's modulus and elongation at break of the films. Scanning electronic microscopy analysis revealed that the film surface morphology with anthocyanin microcapsules had a homogeneous and smooth surface texture compared to the control. The thermogravimetric analysis also showed a slight improvement in the thermal properties of the developed films. Agar well diffusion assay revealed that the developed films exhibit significant inhibition against a broad-spectrum of bacteria. Furthermore, the films composed of gelatine with anthocyanin microcapsules significantly reduced the total viable count of microorganisms in the bean curd during storage for 12 days compared with the control films.
Novelty and scientific contribution: Increasing global awareness of healthy and safe food with minimal synthetic ingredients as preservatives has sparked the search for the use of antimicrobial agents of natural origins in active food packaging material. In this study, a safe and effective active packaging film was developed using an environmentally friendly biopolymer, gelatine film incorporated with microcapsules of Clitoria ternatea-derived anthocyanins as a natural antimicrobial agent. This study demonstrated that such a method is not only able to improve the film physical properties but can also significantly prolong the shelf life of food products by protecting them from microbial spoilage.
Metabolites characterisation of endophytic Phyllosticta fallopiae L67 isolated from Aloe vera with antimicrobial activity on diabetic wound microorganisms

Taher MA, Tan WN, Chear NJ, Leong CR, Rashid SA, Tong WY

Nat Prod Res, 2023 May;37(10):1674-1679.
PMID: 35879820 DOI: 10.1080/14786419.2022.2103127

This study aimed to assess the antimicrobial activity of endophytic Phyllosticta fallopiae L67 isolated from Aloe vera against diabetic wound microorganisms and characterise their active fraction for biologically important metabolites. The dichloromethane (DCM) extract exhibited the most significant activity with inhibition zones ranging from 11.33 to 38.33 mm. The minimal inhibitory and lethality concentrations of DCM extract ranged from 78.13 to 2500.00 µg/ml and 625.00 to 5000.00 µg/ml, respectively. The extract showed teratogenicity and lethality in the zebrafish model, where peritoneal and hepatic oedema occurred at 62.50 µg/ml, and no abnormality appeared at 31.25 µg/ml. The extract also inhibited more than 82% biofilm formation. Bioassay-guided fractionation on DCM extract yielded 18 fractions and the most active fraction was subjected to UPLC-QTOF-MS/MS analysis. Flavones, stilbenes, flavanonols, isoflavonoids, phenolic glycosides and phenol derivatives were detected. In conclusion, endophytic P. fallopiae possessed bioactive metabolites with significant antimicrobial activity against diabetic wound microorganisms.
Effects of Phomopsidione on the Viability, Virulence, and Metabolites Profile of Methicillin-Resistant Staphylococcus aureus (MRSA)

Wei YM, Tong WY, Tan JS, Lim V, Leong CR, Tan WN

Curr Microbiol, 2024 Mar 10;81(4):108.
PMID: 38461425 DOI: 10.1007/s00284-024-03627-7

Methicillin-resistant Staphylococcus aureus (MRSA) infections have become one of the most threatening multidrug-resistant pathogens. Thus, an ongoing search for anti-MRSA compounds remains an urgent need to effectively treating MRSA infections. Phomopsidione, a novel antibiotic isolated from Diaporthe fraxini, has previously demonstrated potent anti-candidal activity. The present study aimed to investigate the effects of phomopsidione on the viability, virulence, and metabolites profile of MRSA. MRSA was sensitive to phomopsidione in a concentration-dependent manner. Phomopsidione exhibited minimum inhibitory concentration and minimum bactericidal concentration of 62.5 and 500.00 µg/mL against MRSA on broth microdilution assay. The compound showed significant reduction in virulence factors production including extracellular polymeric substances quantification, catalase, and lipase. An untargeted metabolomics analysis using liquid chromatography-high resolution mass spectrometry revealed a significant difference in the metabolites profile of MRSA with 13 putatively identified discriminant metabolites. The present study suggested the potential of phomopsidione as a promising anti-MRSA agent.
Sesquiterpenes rich essential oil from Garcinia celebica L. and its cytotoxic and antimicrobial activities

Tan WN, Tan ZH, Zulkifli NI, Nik Mohamed Kamal NNS, Rozman NAS, Tong WY, et al.

Nat Prod Res, 2020 Dec;34(23):3404-3408.
PMID: 30773054 DOI: 10.1080/14786419.2019.1569012

Garcinia celebica L., locally known as "manggis hutan" in Malaysia is widely used in folkloric medicine to treat various diseases. The present study was aimed to examine the chemical composition of the essential oil from the leaves of G. celebica L. (EO-GC) and its cytotoxic and antimicrobial potential. EO-GC obtained by hydrodistillation was analysed using capillary GC and GC-MS. Twenty-two compounds were identified, dominated by α-copaene (61.25%), germacrene D (6.72%) and β-caryophyllene (5.85%). In the in vitro MTT assay, EO-GC exhibited significant anti-proliferative effects towards MCF-7 human breast cancer cells with IC50 value of 45.2 μg/mL. Regarding the antimicrobial activity, it showed better inhibitory effects on Gram-positive bacteria than Gram-negative bacteria and none on the fungi and yeasts tested.
Fulltext Interferon-stimulated gene of 20 kDa protein (ISG20) degrades RNA of hepatitis B virus to impede the replication of HBV in vitro and in vivo

Leong CR, Funami K, Oshiumi H, Mengao D, Takaki H, Matsumoto M, et al.

Oncotarget, 2016 10 18;7(42):68179-68193.
PMID: 27626689 DOI: 10.18632/oncotarget.11907

Hepatitis B virus (HBV) barely induces host interferon (IFN)-stimulated genes (ISGs), which allows efficient HBV replication in the immortalized mouse hepatocytes as per human hepatocytes. Here we found that transfection of Isg20 plasmid robustly inhibits the HBV replication in HBV-infected hepatocytes irrespective of IRF3 or IFN promoter activation. Transfection of Isg20 is thus effective to eradicate HBV in the infected hepatocytes. Transfection of HBV genome or ε-stem of HBV pgRNA (active pgRNA moiety) failed to induce Isg20 in the hepatocytes, while control polyI:C (a viral dsRNA analogue mimic) activated MAVS pathway leading to production of type I IFN and then ISGsg20 via the IFN-α/β receptor (IFNAR). Consistently, addition of IFN-α induced Isg20 and partially suppressed HBV replication in hepatocytes. Chasing HBV RNA, DNA and proteins by blotting indicated that ISG20 expression decreased HBV RNA and replicative DNA in HBV-transfected cells, which resulted in low HBs antigen production and virus titer. The exonuclease domains of ISG20 mainly participated in HBV-RNA decay. In vivo hydrodynamic injection, ISG20 was crucial for suppressing HBV replication without degrading host RNA in the liver. Taken together, ISG20 acts as an innate anti-HBV effector that selectively degrades HBV RNA and blocks replication of infectious HBV particles. ISG20 would be a critical effector for ameliorating chronic HBV infection in the IFN therapy.
Phomopsidione nanoparticles coated contact lenses reduce microbial keratitis causing pathogens

Bin Sahadan MY, Tong WY, Tan WN, Leong CR, Bin Misri MN, Chan M, et al.

Exp Eye Res, 2019 01;178:10-14.
PMID: 30243569 DOI: 10.1016/j.exer.2018.09.011

Microbial keratitis is the infection caused by pathogenic microorganisms that commonly occurs among the contact lens users. Various antimicrobial compounds were coated on contact lenses to kill keratitis causing microorganisms, however these compounds caused several adverse side effects. Hence, the aim of this study is to develop a silicone hydrogel contact lens coated with phomopsidione nanoparticle that inhibit keratitis causing clinical isolates. Phomopsidione nanoparticles were synthesized using polyvinyl alcohol as encapsulant. The nanoparticles showed an average size of 77.45 nm, with neutral surface charge. Two drug release patterns were observed in the drug release profile, which are the initial slow release phase with extended drug release (release rate 46.65 μg/h), and the burst release phase observed on Day 2 (release rate 2224.49 μg/h). This well-regulated drug delivery system enables the control of drug release to meet the therapeutic requirements. On agar diffusion assay, 3 out of 5 test microorganisms were inhibited by phomopsidione nanoparticle coated contact lenses, including two Gram negative bacteria. Besides, all test microorganisms showed at least 99% of growth reduction, with the treatment of the contact lens model. The drug loaded onto the nanoparticles is sufficient to prevent the bacterial growth. In conclusion, this study provides an effective alternative to combat keratitis-causing microorganisms among contact wearers.
Chemical composition and cytotoxic activity of Garcinia atroviridis Griff. ex T. Anders. essential oils in combination with tamoxifen

Tan WN, Lim JQ, Afiqah F, Nik Mohamed Kamal NNS, Abdul Aziz FA, Tong WY, et al.

Nat Prod Res, 2018 Apr;32(7):854-858.
PMID: 28782393 DOI: 10.1080/14786419.2017.1361951

Garcinia atroviridis Griff. ex T. Anders. is used as a medication agent in folkloric medicine. The present study was to examine the chemical composition of the stem bark and leaf of G. atroviridis as well as their cytotoxic effects against MCF-7 cells. The constituents obtained by hydrodistillation were identified using GC-MS. The stem bark oil (EO-SB) composed mainly the palmitoleic acid (51.9%) and palmitic acid (21.9%), while the leaf oil (EO-L) was dominated by (E)-β-farnesene (58.5%) and β-caryophyllene (16.9%). Treatment of MCF-7 cells using EO-L (100 μg/mL) caused more than 50% cell death while EO-SB did not induce cytotoxic effect. EO-L has stimulated the growth of BEAS-2B normal cells, but not in MCF-7 cancerous cells. The IC50 of EO-L in MCF-7 and BEAS-2B cells were 71 and 95 μg/mL, respectively. A combination treatment of EO-L and tamoxifen induced more cell death than the treatment with drug alone at lower doses.
Development of sodium alginate-pectin biodegradable active food packaging film containing cinnamic acid

Tong WY, Ahmad Rafiee AR, Leong CR, Tan WN, Dailin DJ, Almarhoon ZM, et al.

Chemosphere, 2023 Sep;336:139212.
PMID: 37315854 DOI: 10.1016/j.chemosphere.2023.139212

Plastics are still the most popular food packaging material and many of them end up in the environment for a long period. Due to packaging material's inability to inhibit microbial growth, beef often contains microorganisms that affect its aroma, colour and texture. Cinnamic acid is categorized as generally recognised as safe and is permitted for use in food. The development of biodegradable food packaging film with cinnamic acid has never been conducted before. This present study was aimed to develop a biodegradable active packaging material for fresh beef using sodium alginate and pectin. The film was successfully developed with solution casting method. The films' thickness, colour, moisture level, dissolution, water vapour permeability, bending strength and elongation at break were comparable to those of polyethylene plastic film in terms of these attributes. The developed film also showed the degradability in soil of 43.26% in a duration of 15 days. Fourier Transform Infrared (FTIR) spectra showed that cinnamic acid was successfully incorporated with the film. The developed film showed significant inhibitory activity on all test foodborne bacteria. On Hohenstein challenge test, a 51.28-70.45% reduction on bacterial growth was also observed. The antibacterial efficacy of the established film by using fresh beef as food model. The meats wrapped with the film showed significant reduction in bacterial load throughout the experimental period by 84.09%. The colour of the beef also showed significant different between control film and edible film during 5 days test. Beef with control film turned into dark brownish and beef with cinnamic acid turn into light brownish. Sodium alginate and pectin film with cinnamic acid showed good biodegradability and antibacterial activity. Further studies can be conducted to investigate the scalability and commercial viability of this environmental-friendly food packaging materials.
Fulltext Extracellular Vesicles Including Exosomes Regulate Innate Immune Responses to Hepatitis B Virus Infection

Kouwaki T, Fukushima Y, Daito T, Sanada T, Yamamoto N, Mifsud EJ, et al.

Front Immunol, 2016;7:335.
PMID: 27630638 DOI: 10.3389/fimmu.2016.00335

The innate immune system is essential for controlling viral infection. Hepatitis B virus (HBV) persistently infects human hepatocytes and causes hepatocellular carcinoma. However, the innate immune response to HBV infection in vivo remains unclear. Using a tree shrew animal model, we showed that HBV infection induced hepatic interferon (IFN)-γ expression during early infection. Our in vitro study demonstrated that hepatic NK cells produced IFN-γ in response to HBV only in the presence of hepatic F4/80(+) cells. Moreover, extracellular vesicles (EVs) released from HBV-infected hepatocytes contained viral nucleic acids and induced NKG2D ligand expression in macrophages by stimulating MyD88, TICAM-1, and MAVS-dependent pathways. In addition, depletion of exosomes from EVs markedly reduced NKG2D ligand expression, suggesting the importance of exosomes for NK cell activation. In contrast, infection of hepatocytes with HBV increased immunoregulatory microRNA levels in EVs and exosomes, which were transferred to macrophages, thereby suppressing IL-12p35 mRNA expression in macrophages to counteract the host innate immune response. IFN-γ increased the hepatic expression of DDX60 and augmented the DDX60-dependent degradation of cytoplasmic HBV RNA. Our results elucidated the crucial role of exosomes in antiviral innate immune response against HBV.
Thymol-Loaded Polymeric Nanoparticles Improve the Postharvest Microbiological Safety of Blueberries

Ab Rashid S, Tong WY, Leong CR, Tan WN, Lee CK, Anuar MR, et al.

Food Technol Biotechnol, 2023 Jun;61(2):151-159.
PMID: 37457903 DOI: 10.17113/ftb.61.02.23.7595

RESEARCH BACKGROUND: The presence of Yersinia enterocolitica on raw food products raises the concern of yersiniosis as most of the berries are consumed raw. This is a challenging issue from the food safety aspect since it could increase the occurrence of foodborne diseases among humans. Thus, it is crucial to implement an effective sanitation before the packaging.
EXPERIMENTAL APPROACH: This study aims to synthesize and characterize thymol-loaded polyvinyl alcohol (Thy/PVA) nanoparticles as a sanitizer for postharvest treatment of blueberries. Thy/PVA nanoparticles were characterized by spectroscopic and microscopic approaches, prior to the analyses of antimicrobial properties.
RESULTS AND CONCLUSIONS: The diameter size of the nanoparticles was on average 84.7 nm, with a surface charge of -11.73 mV. Based on Fourier transform infrared (FTIR) measurement, the Thy/PVA nanoparticles notably shifted to the frequency of 3275.70, 2869.66, 1651.02 and 1090.52 cm-1. A rapid burst was observed in the first hour of release study, and 74.9 % thymol was released from the PVA nanoparticles. The largest inhibition zone was displayed by methicillin-resistant Staphylococcus aureus (MRSA), followed by Y. enterocolitica and Salmonella typhi. However, amongst these bacteria, the inhibition and killing of Y. enterocolitica required a lower concentration of Thy/PVA nanoparticles. The treatment successfully reduced the bacterial load of Y. enterocolitica on blueberries by 100 %.
NOVELTY AND SCIENTIFIC CONTRIBUTION: Thymol is a plant-based chemical without reported adverse effects to humans. In this study, by using the nanotechnology method of encapsulation with PVA, we improved the stability and physicochemical properties of thymol. This nanoparticle-based sanitizer could potentially promote the postharvest microbiological safety of raw berries, which may become an alternative practice of food safety.
Nanoparticle-laden contact lens for controlled release of vancomycin with enhanced antibiotic efficacy

Tong WY, Tan WN, Kamarul Azizi MA, Leong CR, El Azab IH, Lim JW, et al.

Chemosphere, 2023 Oct;338:139492.
PMID: 37451643 DOI: 10.1016/j.chemosphere.2023.139492

Vancomycin is the last resort antibiotic for the treatment of severe bacterial keratitis. Its clinical application is limited due to its hydrophilicity and high molecular weight. To overcome this, this study aims to develop nanoparticles-laden contact lens for controlled ocular delivery of vancomycin. Polyvinyl alcohol (PVA) was used as encapsulant material. The nanoparticles had a negative surface charge and an average size of 147.6 nm. A satisfactory encapsulation efficiency (61.24%) was obtained. The release profile was observed to be slow and sustained, with a release rate of 1.29 μL mg-1 h-1 for 48 h. Five out of 6 test bacteria were suppressed by vancomycin nanoparticles-laden contact lens. Vancomycin is generally ineffective against Gram-negative bacteria and unable to pass through the outer membrane barrier. In this study, vancomycin inhibited Proteus mirabilis and Pseudomonas aeruginosa. Nano-encapsulation enables vancomycin to penetrate the Gram-negative cell wall and further destroy the bacterial cells. On Hohenstein challenge test, all test bacteria exhibited significant reduction in growth when exposed to vancomycin nanoparticles-laden contact lens. This study created an effective and long-lasting vancomycin delivery system via silicone hydrogel contact lenses, by using PVA as encapsulant. The antibiotic efficacy and vancomycin release should be further studied using ocular in vivo models.
Fulltext Homalomena pineodora essential oil nanoparticle inhibits diabetic wound pathogens

Rozman NAS, Tong WY, Leong CR, Anuar MR, Karim S, Ong SK, et al.

Sci Rep, 2020 02 24;10(1):3307.
PMID: 32094395 DOI: 10.1038/s41598-020-60364-0

Essential oil of Homalomena pineodora inhibits diabetic pathogens; however, the activity was not sustainable when applied as wound dressing. This study aims to synthesise the essential oil nanoparticle using chitosan. The nanoparticles were synthesised with ion gelation method, confirmed by spectroscopic analysis. The spherical nanoparticles display a size of 70 nm, with strong surface charge of +24.10 mV. The nanoparticles showed an initial burst release followed by a slow release pattern for 72 h, following the first order of kinetic. The release behaviour was ideal for wound dressing. The antimicrobial activity was broad spectrum. The formation of nanoparticle enhanced the antimicrobial efficacy of the essential oil. The nanoparticle also showed a concentration-dependent killing behaviour on time-kill assay. In the 3D collagen wound models, the nanoparticles reduced the microbial growth by 60-80%. In conclusion, H. pineodora nanoparticles showed pharmaceutical potential in inhibiting microbial growth on diabetic ulcers.

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