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Quantitative characterization of chitosan in the skin by Fourier-transform infrared spectroscopic imaging and ninhydrin assay: application in transdermal sciences

Nawaz A, Wong TW

J Microsc, 2016 07;263(1):34-42.
PMID: 26695532 DOI: 10.1111/jmi.12371

The chitosan has been used as the primary excipient in transdermal particulate dosage form design. Its distribution pattern across the epidermis and dermis is not easily accessible through chemical assay and limited to radiolabelled molecules via quantitative autoradiography. This study explored Fourier-transform infrared spectroscopy imaging technique with built-in microscope as the means to examine chitosan molecular distribution over epidermis and dermis with the aid of histology operation. Fourier-transform infrared spectroscopy skin imaging was conducted using chitosan of varying molecular weights, deacetylation degrees, particle sizes and zeta potentials, obtained via microwave ligation of polymer chains at solution state. Both skin permeation and retention characteristics of chitosan increased with the use of smaller chitosan molecules with reduced acetyl content and size, and increased positive charge density. The ratio of epidermal to dermal chitosan content decreased with the use of these chitosan molecules as their accumulation in dermis (3.90% to 18.22%) was raised to a greater extent than epidermis (0.62% to 1.92%). A larger dermal chitosan accumulation nonetheless did not promote the transdermal polymer passage more than the epidermal chitosan. A small increase in epidermal chitosan content apparently could fluidize the stratum corneum and was more essential to dictate molecular permeation into dermis and systemic circulation. The histology technique aided Fourier-transform infrared spectroscopy imaging approach introduces a new dimension to the mechanistic aspect of chitosan in transdermal delivery.
Chitosan-Carboxymethyl-5-Fluorouracil-Folate Conjugate Particles: Microwave Modulated Uptake by Skin and Melanoma Cells

Nawaz A, Wong TW

J Invest Dermatol, 2018 11;138(11):2412-2422.
PMID: 29857069 DOI: 10.1016/j.jid.2018.04.037

5-Fluorouracil delivery profiles in the form of chitosan-folate submicron particles through skin and melanoma cells in vitro were examined using microwaves as the penetration enhancer. The in vivo pharmacokinetic profile of 5-fluorouracil was also determined. Chitosan-carboxymethyl-5-fluorouracil-folate conjugate was synthesized and processed into submicron particles by spray-drying technique. The size, zeta potential, morphology, drug content, and drug release, as well as skin permeation and retention, pharmacokinetics, in vitro SKMEL-28 melanoma cell line cytotoxicity, and intracellular trafficking profiles of drug/particles, were examined as a function of skin/melanoma cell treatment by microwaves at 2,450 MHz for 5 + 5 minutes. The level of skin drug/particle retention in vitro and in vivo increased in skin treated by microwaves. This was facilitated by the drug conjugating to chitosan and microwaves fluidizing both the protein and lipid domains of epidermis and dermis. The uptake of chitosan-folate particles by melanoma cells was mediated via lipid raft route. It was promoted by microwaves, which fluidized the lipid and protein regimes of the cell membrane, and this increased drug cytotoxicity. In vivo pharmacokinetic study indicated skin treatment by microwave-enhanced drug retention but not permeation. The combination of microwaves and submicron particles synergized skin drug retention and intracellular drug delivery.
Microwave as skin permeation enhancer for transdermal drug delivery of chitosan-5-fluorouracil nanoparticles

Nawaz A, Wong TW

Carbohydr Polym, 2017 Feb 10;157:906-919.
PMID: 27988008 DOI: 10.1016/j.carbpol.2016.09.080

This study investigated transdermal drug delivery mechanisms of chitosan nanoparticles with the synergistic action of microwave in skin modification. Chitosan nanoparticles, with free or conjugated 5-fluorouracil, were prepared by nanospray-drying technique. Their transdermal drug delivery profiles across untreated and microwave-treated skins (2450MHz 5min, 5+5min; 3985MHz 5min) were examined. Both constituent materials of nanoparticles and drug encapsulation were required to succeed transdermal drug delivery. The drug transport was mediated via nanoparticles carrying drug across the skin and/or diffusion of earlier released drug molecules from skin surfaces. The drug/nanoparticles transport was facilitated through constituent nanoparticles and microwave fluidizing protein/lipid domains of epidermis and dermis (OH, NH, CH, CN) and dermal trans-to-gauche lipid conformational changes. The microwave induced marked changes to the skin ceramide content homogeneity. The chitosan nanoparticles largely affected the palmitic acid and keratin domains. Combined microwave and nanotechnologies synergize transdermal drug delivery.
Fulltext Outcome of surgical treatment of pelvic osteosarcoma: hospital universiti sains malaysia experience

Ariff M, Zulmi W, Faisham W, Nor Azman M, Nawaz A

Malays Orthop J, 2013 Mar;7(1):56-62.
PMID: 25722809 MyJurnal DOI: 10.5704/MOJ.1303.018

We reviewed the surgical treatment and outcomes of 13 patients with pelvic osteosarcoma treated in our centre in the past decade. The study sample included 9 males and 4 females with a mean age of 28.1 years. Four patients had ileal lesions, five had acetabulum lesions, one had a ischiopubis lesion, and three had involvement of the whole hemipelvis. Seven patients presented with distant metastases at diagnosis. Limb salvage was performed in 6 patients and amputation in 7. In 60% of cases in the limb salvage surgery group, we attempted wide resection with positive microscopic margin compared to only 16.7% in the amputation group. Local recurrence was higher in the limb salvage group. Overall survival was 18 months for mean follow up of 14.8 months. Median survival was 19 months in the limb salvage group compared to 9 months in amputation group. The outcome of surgical treatment of pelvic osteosarcoma remains poor despite advancements in musculoskeletal oncology treatment.
Fulltext Early Functional Outcome of Resection and Endoprosthesis Replacement for Primary Tumor around the Knee

Sharil A, Nawaz A, Nor Azman M, Zulmi W, Faisham W

Malays Orthop J, 2013 Mar;7(1):30-5.
PMID: 25722804 MyJurnal DOI: 10.5704/MOJ.1303.013

We evaluated functional outcomes for patients who underwent surgery for resection and endoprosthesis replacement for primary tumours around the knee. We used the Musculoskeletal Tumour Society Scoring System (MSTS) for functional evaluations to compare differences between distal femur (DF) and proximal tibia (PT) placements. The study sample included 34 cases of distal femur and 20 cases of proximal tibia endoprosthesis replacement. Primary tumours were classified as follows: 33 osteosarcoma, 20 stage III giant cell tumour (GCT) and one case of mesenchymal chondrosarcoma. The mean MSTS score for both DF and PT endoprosthesis together was 21.13 (70.43%), and The MSTS scores for DF was 21.94 (73.13%) and PT was 19.75 (65.83%) Infection developed in 7 cases and 5 of which were PT endoprosthesis cases. Three deep infections required early, two-stage revision and resulted in poor MSTS scores. We conclude that endoprosthesis replacement for primary bone tumours had early good to excellent functional outcome. There were no differences in functional outcomes when comparing distal femur endoprostheses with proximal tibia endoprostheses.
KEY WORDS: functional outcome, bone tumour, knee, and endoprosthesis.
Nanocarriers and their Actions to Improve Skin Permeability and Transdermal Drug Delivery

Khan NR, Harun MS, Nawaz A, Harjoh N, Wong TW

Curr Pharm Des, 2015;21(20):2848-66.
PMID: 25925113

Transdermal drug delivery is impeded by the natural barrier of epidermis namely stratum corneum. This limits the route to transport of drugs with a log octanol-water partition coefficient of 1 to 3, molecular weight of less than 500 Da and melting point of less than 200°C. Nanotechnology has received widespread investigation as nanocarriers are deemed to be able to fluidize the stratum corneum as a function of size, shape, surface charges, and hydrophilicity-hydrophobicity balance, while delivering drugs across the skin barrier. This review provides an overview and update on the latest designs of liposomes, ethosomes, transfersomes, niosomes, magnetosomes, oilin- water nanoemulsions, water-in-oil nanoemulsions, bicontinuous nanoemulsions, covalently crosslinked polysaccharide nanoparticles, ionically crosslinked polysaccharide nanoparticles, polyelectrolyte coacervated nanoparticles and hydrophobically modified polysaccharide nanoparticles with respect to their ability to fuse or fluidize lipid/protein/tight junction regimes of skin, and effect changes in skin permeability and drug flux. Universal relationships of nanocarrier size, zeta potential and chemical composition on transdermal permeation characteristics of drugs will be developed and discussed.
In Vitro Investigation of Influences of Chitosan Nanoparticles on Fluorescein Permeation into Alveolar Macrophages

Chachuli SH, Nawaz A, Shah K, Naharudin I, Wong TW

Pharm Res, 2016 06;33(6):1497-508.
PMID: 26951565 DOI: 10.1007/s11095-016-1893-5

PURPOSE: Pulmonary infection namely tuberculosis is characterized by alveolar macrophages harboring a large microbe population. The chitosan nanoparticles exhibit fast extracellular drug release in aqueous biological milieu. This study investigated the matrix effects of chitosan nanoparticles on extracellular drug diffusion into macrophages.
METHODS: Oligo, low, medium and high molecular weight chitosan nanoparticles were prepared by nanospray drying technique. These nanoparticles were incubated with alveolar macrophages in vitro and had model drug sodium fluorescein added into the same cell culture. The diffusion characteristics of sodium fluorescein and nanoparticle behavior were investigated using fluorescence microscopy, scanning electron microscopy, differential scanning calorimetry and Fourier transform infrared spectroscopy techniques.
RESULTS: The oligochitosan nanoparticles enabled macrophage membrane fluidization with the extent of sodium fluorescein entry into macrophages being directly governed by the nanoparticle loading. Using nanoparticles made of higher molecular weight chitosan, sodium fluorescein permeation into macrophages was delayed due to viscous chitosan diffusion barrier at membrane boundary.
CONCLUSION: Macrophage-chitosan nanoparticle interaction at membrane interface dictates drug migration into cellular domains.
Fulltext Formulation and Characterization of Ethyl Cellulose-Based Patches Containing Curcumin-Chitosan Nanoparticles for the Possible Management of Inflammation via Skin Delivery

Nawaz A, Latif MS, Shah MKA, Elsayed TM, Ahmad S, Khan HA

Gels, 2023 Mar 06;9(3).
PMID: 36975650 DOI: 10.3390/gels9030201

Curcumin, a natural phenolic compound, exhibits poor absorption and extensive first pass metabolism after oral administration. In the present study, curcumin-chitosan nanoparticles (cur-cs-np) were prepared and incorporated into ethyl cellulose patches for the management of inflammation via skin delivery. Ionic gelation method was used for the preparation of nanoparticles. The prepared nanoparticles were evaluated for size, zetapotential, surface morphology, drug content, and % encapsulation efficiency. The nanoparticles were then incorporated into ethyl cellulose-based patches using solvent evaporation technique. ATR-FTIR was used to study/assess incompatibility between drug and excipients. The prepared patches were evaluated physiochemically. The in vitro release, ex vivo permeation, and skin drug retention studies were carried out using Franz diffusion cells and rat skin as permeable membrane. The prepared nanoparticles were spherical, with particle size in the range of 203-229 nm, zetapotential 25-36 mV, and PDI 0.27-0.29 Mw/Mn. The drug content and %EE were 53% and 59%. Nanoparticles incorporated patches are smooth, flexible, and homogenous. The in vitro release and ex vivo permeation of curcumin from nanoparticles were higher than the patches, whereas the skin retention of curcumin was significantly higher in case of patches. The developed patches deliver cur-cs-np into the skin, where nanoparticles interact with skin negative charges and hence result in higher and prolonged retention in the skin. The higher concentration of drug in the skin helps in better management of inflammation. This was shown by anti-inflammatory activity. The inflammation (volume of paw) was significantly reduced when using patches as compared to nanoparticles. It was concluded that the incorporation of cur-cs-np into ethyl cellulose-based patches results in controlled release and hence enhanced anti-inflammatory activity.
Investigating the crude oil biodegradation performance in bioreactor by using a consortium of symbiotic bacteria

Chuah LF, Nawaz A, Dailin DJ, Oloruntobi O, Habila MA, Tong WY, et al.

Chemosphere, 2023 Oct;337:139293.
PMID: 37369285 DOI: 10.1016/j.chemosphere.2023.139293

Crude oil pollution is one of the most serious environmental issues today, and the clean-up procedure is perhaps the most difficult. Within one to three weeks, the vast majority of oil bacteria may degrade approximately 60% of the crude oil, leaving approximately 40% intact. The by-product metabolites produced during the breakdown of oil are essentially organic molecules in nature. These metabolites inhibit its enzymes, preventing the oil bacteria from further degrading the oil. By combining a variety of different oils with heterotrophic bacteria in a bioreactor, the rate of crude oil biodegradation was accelerated. In this study, two strains of oil-resistant, heterotrophic bacteria (OG1 and OG2-Erythrobacter citreus) and a bacterium that uses hydrocarbons (AR3-Pseudomonas pseudoalcaligenes) were used. Gas chromatography-mass spectroscopy was used to investigate the effectiveness of this consortium of symbiotic bacteria in the biodegradation of crude oil. According to gravimetric and gas chromatography analyses, the consortium bacteria digested 69.6% of the crude oil in the bioreactor, while the AR3 single strain was only able to destroy 61.9% of it. Under the same experimental conditions, consortium bacteria degraded approximately 84550.851 ppb (96.3%) of 16 aliphatic hydrocarbons and 9333.178 ppb (70.5%) of 16 aromatic hydrocarbons in the bioreactor. It may be inferred that the novel consortium of symbiotic bacteria accelerated the biodegradation process and had great potential for use in increasing the bioremediation of hydrocarbon-contaminated locations.
Fulltext Prescription drug dependence with and without concurrent illicit drug use: a multicenter cross-sectional survey among an addiction treatment seeking population

Nawaz A, Nielsen S, Mehmood T, Abdullah A, Ahmed A, Ullah W, et al.

Front Psychiatry, 2023;14:1133606.
PMID: 37324815 DOI: 10.3389/fpsyt.2023.1133606

BACKGROUND: Dependence on prescription drugs and illicit drugs imposes a global health and social burden. Despite accumulating evidence of prescription drugs and illicit drugs dependence, none of the systematized studies has explored the magnitude of this problem in Pakistan. The aim is to investigate the extent and associated factors of prescription drug dependence (PDD), as opposed to concomitant prescription drug dependence and illicit drug use (PIDU), within a sample of individuals seeking addiction treatment.
METHODS: The cross sectional study was conducted on the sample recruited from three drug treatment centers in Pakistan. Face-to-face interviews were conducted with participants who met ICD-10 criteria for prescription drug dependence. Several aspects like substance use histories, negative health outcomes, patient attitude, pharmacy and physician practices also collected to predict the determinants of (PDD). Binomial logistic regression models examined the factors associated with PDD and PIDU.
RESULTS: Of the 537 treatment seeking individuals interviewed at baseline, close to one third (178, 33.3%) met criteria for dependence on prescription drugs. The majority of the participants were male (93.3%), average age of 31 years, having urban residence (67.4%). Among participants who met criteria for dependence on prescription drugs (71.9%), reported benzodiazepines as the most frequently used drug, followed by narcotic analgesics (56.8%), cannabis/marijuana (45.5%), and heroin (41.5%). The patients reported alprazolam, buprenorphine, nalbuphine, and pentazocin use as alternatives to illicit drugs. PDD was significantly negatively associated with injectable route (OR = 0.281, 95% CI, 0.079-0.993) and psychotic symptoms (OR = 0.315, 95% CI, 0.100, 0.986). This implies that PDD is less likely to be associated with an injectable route and psychotic symptoms in contrast to PIDU. Pain, depression and sleep disorder were primary reasons for PDD. PDD was associated with the attitude that prescription drugs are safer than illicit drugs (OR = 4.057, 95%CI, 1.254-13.122) and PDD was associated with being on professional terms (i.e., having an established relationship) with pharmaceutical drugs retailers for acquisition of prescription drugs.
DISCUSSION AND CONCLUSION: The study found benzodiazepine and opioid dependence in sub sample of addiction treatment seekers. The results have implications for drug policy and intervention strategies for preventing and treating drug use disorders.
Editorial: Sustainable and intelligent plant health management in Asia (2022)

Yeh KH, Travlos I, Nawaz A, Chang SC, Chao HC

Front Plant Sci, 2023;14:1244869.
PMID: 37645468 DOI: 10.3389/fpls.2023.1244869
Fulltext Ethyl Cellulose and Hydroxypropyl Methyl Cellulose Blended Methotrexate-Loaded Transdermal Patches: In Vitro and Ex Vivo

Latif MS, Azad AK, Nawaz A, Rashid SA, Rahman MH, Al Omar SY, et al.

Polymers (Basel), 2021 Oct 09;13(20).
PMID: 34685214 DOI: 10.3390/polym13203455

Transdermal drug delivery systems (TDDSs) have become innovative, fascinating drug delivery methods intended for skin application to achieve systemic effects. TDDSs overcome the drawbacks associated with oral and parenteral routes of drug administration. The current investigation aimed to design, evaluate and optimize methotrexate (MTX)-loaded transdermal-type patches having ethyl cellulose (EC) and hydroxypropyl methyl cellulose (HPMC) at different concentrations for the local management of psoriasis. In vitro release and ex vivo permeation studies were carried out for the formulated patches. Various formulations (F1-F9) were developed using different concentrations of HPMC and EC. The F1 formulation having a 1:1 polymer concentration ratio served as the control formulation. ATR-FTIR analysis was performed to study drug-polymer interactions, and it was found that the drug and polymers were compatible with each other. The formulated patches were further investigated for their physicochemical parameters, in vitro release and ex vivo diffusion characteristics. Different parameters, such as surface pH, physical appearance, thickness, weight uniformity, percent moisture absorption, percent moisture loss, folding endurance, skin irritation, stability and drug content uniformity, were studied. From the hydrophilic mixture, it was observed that viscosity has a direct influence on drug release. Among all formulated patches, the F5 formulation exhibited 82.71% drug release in a sustained-release fashion and followed an anomalous non-Fickian diffusion. The permeation data of the F5 formulation exhibited about a 36.55% cumulative amount of percent drug permeated. The skin showed high retention for the F5 formulation (15.1%). The stability study indicated that all prepared formulations had very good stability for a period of 180 days. Therefore, it was concluded from the present study that methotrexate-loaded transdermal patches with EC and HPMC as polymers at different concentrations suit TDDSs ideally and improve patient compliance for the local management of psoriasis.
Fulltext Clarithromycin and Pantoprazole Gastro-Retentive Floating Bilayer Tablet for the Treatment of Helicobacter Pylori: Formulation and Characterization

Ullah G, Nawaz A, Latif MS, Shah KU, Ahmad S, Javed F, et al.

Gels, 2023 Jan 04;9(1).
PMID: 36661809 DOI: 10.3390/gels9010043

Bilayer/multilayer tablets have been introduced to formulate incompatible components for compound preparations, but they are now more commonly used to tailor drug release. This research aimed to formulate a novel gastro-retentive tablet to deliver a combination of a fixed dose of two drugs to eliminate Helicobacter pylori (H. pylori) in the gastrointestinal tract. The bilayer tablets were prepared by means of the direct compression technique. The controlled-release bilayer tablets were prepared using various hydrophilic swellable polymers (sodium alginate, chitosan, and HPMC-K15M) alone and in combination to investigate the percent of swelling behavior and average drug release. The weight of the controlled-release floating layer was 500 mg, whereas the weight of the floating tablets of pantoprazole was 100 mg. To develop the most-effective formulation, the effects of the experimental components on the floating lag time, the total floating time, T 50%, and the amount of drug release were investigated. The drugs' and excipients' compatibilities were evaluated using ATR-FTIR and DSC. Pre-compression and post-compression testing were carried out for the prepared tablets, and they were subjected to in vitro characterization studies. The pantoprazole layer of the prepared tablet demonstrated drug release (95%) in 2 h, whereas clarithromycin demonstrated sustained drug release (83%) for up to 24 h (F7). The present study concluded that the combination of sodium alginate, chitosan, and HPMC polymers (1:1:1) resulted in a gastro-retentive and controlled-release drug delivery system of the drug combination. Thus, the formulation of the floating bilayer tablets successfully resulted in a biphasic drug release. Moreover, the formulation (F7) offered the combination of two drugs in a single-tablet formulation containing various polymers (sodium alginate, chitosan, and HPMC polymers) as the best treatment option for local infections such as gastric ulcers.
Fulltext Optimization of Chitosan-Decorated Solid Lipid Nanoparticles for Improved Flurbiprofen Transdermal Delivery

Burki FA, Shah KU, Razaque G, Shah SU, Nawaz A, Saeed MD, et al.

ACS Omega, 2023 Jun 06;8(22):19302-19310.
PMID: 37305303 DOI: 10.1021/acsomega.2c08135

Transdermal delivery is a potential alternative route to oral administration for drugs associated with stomach discomfort, such as flurbiprofen, a widely nonsteroidal anti-inflammatory drug (NSAID). This study aimed to design solid lipid nanoparticle (SLN) transdermal formulations of flurbiprofen. Chitosan-coated SLNs were prepared by the solvent emulsification method, and their properties and permeation profiles across the excised rat skin were characterized. The particle size of uncoated SLNs was at 695 ± 4.65 nm, which increased to 714 ± 6.13, 847 ± 5.38, and 900 ± 8.65 nm upon coating with 0.05, 0.10, and 0.20% of chitosan, respectively. The drug association efficiency was improved when a higher concentration of chitosan was employed over SLN droplets that endowed a higher affinity of flurbiprofen with chitosan. The drug release was significantly retarded as compared to the uncoated entities and followed non-Fickian anomalous diffusion that was depicted by "n" values of >0.5 and <1. Also, the total permeation of chitosan-coated SLNs (F7-F9) was significantly higher than that of the noncoated formulation (F5). Overall, this study has successfully designed a suitable carrier system of chitosan-coated SLNs that provide insight into the current conventional therapeutic approaches and suggest new directions for the advancements in transdermal drug delivery systems for improved permeation of flurbiprofen.
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.
Enhancing coastal ecosystem resilience: Investigating the interplay between safety criteria and ferry employee's perceptions to address climate change impacts

Azmi MA, Mokhtar K, Osnin NA, Razali Chan S, Albasher G, Ali A, et al.

Environ Res, 2023 Dec 01;238(Pt 1):117074.
PMID: 37678506 DOI: 10.1016/j.envres.2023.117074

Coastal ecosystems play an important part in mitigating the effects of climate change. Coastal ecosystems are becoming more susceptible to climate change impacts due to human activities and maritime accidents. The global shipping industry, especially in Southeast Asia, has witnessed numerous accidents, particularly involving passenger ferries, resulting in injuries and fatalities in recent years. In order to mitigate the impact of climate change on coastal ecosystems, this study aimed to evaluate the relationship between employees' perceptions of safety criteria and their own safety behaviour on Langkawi Island, Malaysia. A straightforward random sampling technique was employed to collect data from 112 ferry employees aboard Malaysian-registered passenger boats by administering questionnaires. The findings shed light on the strong connection between providing safety instructions for passengers and safety behaviour among ferry workers. Safety instructions should contain climate-related information to successfully address the effects of climate change. The instructions might include guidance on responding to extreme weather events and understanding the potential consequences of sea-level rise on coastal communities. The ferry company staff should also expand their safe behaviour concept to include training and preparation for climate-related incidents. The need to recognise the interconnectedness between climate change, ferry safety and the protection of coastal ecosystems is emphasised in this study. The findings can be utilised by policymakers, regulatory agencies and ferry operators to design holistic policies that improve safety behaviour, minimise maritime mishaps and preserve the long-term sustainability of coastal ecosystems in the face of difficulties posed by climate change.
Evaluation on microalgae for the production of bio-chemicals and electricity

Khairuddin F, Zaharah Mohd Fuzi SF, Ahmad A, Oon LK, Bokhari A, Dailin DJ, et al.

Chemosphere, 2024 Feb;350:141007.
PMID: 38141667 DOI: 10.1016/j.chemosphere.2023.141007

Recent advancement in biophotovoltaic systems using microalgae, coupled with biorefinery approach, would improve economy-feasibility in production. The major concern is its commercial strength in terms of scalability, strain selection and extraction procedure cost. It must compete with conventional feedstocks such as fossil fuels. This project proposes to enhance the economic feasibility of microalgae-based biorefinery by evaluating their performance for bio-electricity, bio-diesel and carotenoids production in a single cycle. The first part of the study was to construct and select a Bio-bottle Voltaic (BBV) device that would allow microalgae to grow and produce bioproducts, as well as generate the maximum current output reading derived from the microalgae's photosynthesis process. The second phase consisted of a 25-day investigation into the biorefinery performance of six different microalgal species in producing bio-electricity, bio-diesel and carotenoid in a prototype BBV device. The prototype BBV device with aluminium foil and pencil lead as its anode and cathode produced the highest carotenoid and biodiesel component production from the two microalgae tested, according to the results of the first phase of the experiment. In the second portion of the study, Scenedesmus dimorphus and Chlorella vulgaris were identified as the two microalgae most capable of maintaining their growth throughout the experiment. The maximum current reading observed for C. vulgaris was 653 mV. High Performance Liquid Chromatography analysis showed four major carotenoid compounds found which were Neoxanthin, Cantaxanthin, Astaxanthin and 9-cis antheraxanthin, and the highest carotenoid producer was C. vulgaris which recorded at 1.73 μg/mL. C. vulgaris recorded as the most alkanes producer with 22 compounds detected and Heptacosane and Heneicosane as the two major biodiesel compounds found in the extracts. Evaluation of C. vulgaris data showed that it has enormous potential for microalgal biorefinery candidates. Further ongoing research and development efforts for C. vulgaris will improve the economic viability of microalgae-based industries and reduce reliance on depleted fossil fuels.
Fulltext Methotrexate-Loaded Gelatin and Polyvinyl Alcohol (Gel/PVA) Hydrogel as a pH-Sensitive Matrix

Akhlaq M, Azad AK, Ullah I, Nawaz A, Safdar M, Bhattacharya T, et al.

Polymers (Basel), 2021 Jul 14;13(14).
PMID: 34301057 DOI: 10.3390/polym13142300

The aim was to formulate and evaluate Gel/PVA hydrogels as a pH-sensitive matrix to deliver methotrexate (MTX) to colon. The primed Gel/PVA hydrogels were subjected to evaluation for swelling behavior, diffusion coefficient, sol-gel characteristic and porosity using an acidic (pH 1.2) and phosphate buffer (PBS) (pH 6.8 & pH 7.4) media. Fourier transform infrared spectroscopy (FTIR) and thermal gravimetric analysis (TGA) were performed to evaluate the chemical compatibility of the Gel/PVA hydrogel. The shape alteration and release of Gel/PVA hydrogel was conducted at pH 1.2, pH 6.8 and pH 7.4. The drug release kinetic mechanism was determined using various kinetic equations. The physicochemical evaluation tests and drug release profile results were found to be significant (p < 0.01). However, it was dependent on the polymers' concentration, the pH of the release media and the amount of the cross-linking agent. Hydrogels containing the maximum amount of gel showed a dynamic equilibrium of 10.09 ± 0.18 and drug release of 93.75 ± 0.13% at pH 1.2. The kinetic models showed the release of MTX from the Gel/PVA hydrogel was non-Fickian. The results confirmed that the newly formed Gel/PVA hydrogels are potential drug delivery systems for a controlled delivery of MTX to the colon.
Chitosan-Coated 5-Fluorouracil Incorporated Emulsions as Transdermal Drug Delivery Matrices

Khan TA, Azad AK, Fuloria S, Nawaz A, Subramaniyan V, Akhlaq M, et al.

Polymers (Basel), 2021 Sep 29;13(19).
PMID: 34641162 DOI: 10.3390/polym13193345

The purpose of the present study was to develop emulsions encapsulated by chitosan on the outer surface of a nano droplet containing 5-fluorouracil (5-FU) as a model drug. The emulsions were characterized in terms of size, pH and viscosity and were evaluated for their physicochemical properties such as drug release and skin permeation in vitro. The emulsions containing tween 80 (T80), sodium lauryl sulfate, span 20, and a combination of polyethylene glycol (PEG) and T20 exhibited a release of 88%, 86%, 90% and 92%, respectively. Chitosan-modified emulsions considerably controlled the release of 5-FU compared to a 5-FU solution (p < 0.05). All the formulations enabled transportation of 5-FU through a rat's skin. The combination (T80, PEG) formulation showed a good penetration profile. Different surfactants showed variable degrees of skin drug retention. The ATR-FTIR spectrograms revealed that the emulsions mainly affected the fluidization of lipids and proteins of the stratum corneum (SC) that lead to enhanced drug permeation and retention across the skin. The present study concludes that the emulsions containing a combination of surfactants (Tween) and a co-surfactant (PEG) exhibited the best penetration profile, prevented the premature release of drugs from the nano droplet, enhanced the permeation and the retention of the drug across the skin and had great potential for transdermal drug delivery. Therefore, chitosan-coated 5-FU emulsions represent an excellent possibility to deliver a model drug as a transdermal delivery system.
Fulltext Formulation Development, Characterization and Antifungal Evaluation of Chitosan NPs for Topical Delivery of Voriconazole In Vitro and Ex Vivo

Shah MKA, Azad AK, Nawaz A, Ullah S, Latif MS, Rahman H, et al.

Polymers (Basel), 2021 Dec 30;14(1).
PMID: 35012154 DOI: 10.3390/polym14010135

This study aims to develop chitosan-based voriconazole nanoparticles (NPs) using spray-drying technique. The effect of surfactants and polymers on the physicochemical properties, in vitro release, and permeation of NPs was investigated. The prepared NPs containing various surfactants and polymers (e.g., Tween 20 (T20), Tween 80 (T80), sodium lauryl sulfate (SLS), propylene glycol (PG), and Polyethylene glycol-4000 (PEG-4000)) were physiochemically evaluated for size, zeta potential, drug content, percent entrapment efficiency, in vitro release, and permeation across rats' skin. A Franz diffusion cell was used for evaluating the in vitro release and permeation profile. The voriconazole-loaded NPs were investigated for antifungal activity against Candida albicans (C. albicans). The prepared NPs were in the nano range (i.e., 160-500 nm) and positively charged. Images taken by a scanning electron microscope showed that all prepared NPs were spherical and smooth. The drug content of NPs ranged from 75% to 90%. Nanoparticle formulations exhibited a good in vitro release profile and transport voriconazole across the rat's skin in a slow control release manner. The NPs containing SLS, T80, and PG exhibited the best penetration and skin retention profile. In addition, the formulation exhibited a potential antifungal effect against C. albicans. It was concluded that the development of chitosan NPs has a great potential for the topical delivery of voriconazole against fungal infection.

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