Publications by authors named "Mohammed Yousuf"

40 Publications

Topical drug delivery: History, percutaneous absorption, and product development.

Adv Drug Deliv Rev 2021 Aug 14;177:113929. Epub 2021 Aug 14.

Therapeutics Research Centre, The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD, Australia.

Topical products, widely used to manage skin conditions, have evolved from simple potions to sophisticated delivery systems. Their development has been facilitated by advances in percutaneous absorption and product design based on an increasingly mechanistic understanding of drug-product-skin interactions, associated experiments, and a quality-by-design framework. Topical drug delivery involves drug transport from a product on the skin to a local target site and then clearance by diffusion, metabolism, and the dermal circulation to the rest of the body and deeper tissues. Insights have been provided by Quantitative Structure Permeability Relationships (QSPR), molecular dynamics simulations, and dermal Physiologically Based PharmacoKinetics (PBPK). Currently, generic product equivalents of reference-listed products dominate the topical delivery market. There is an increasing regulatory interest in understanding topical product delivery behavior under 'in use' conditions and predicting in vivo response for population variations in skin barrier function and response using in silico and in vitro findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.addr.2021.113929DOI Listing
August 2021

Mortality and Attrition Rates within the First Year of Antiretroviral Therapy Initiation among People Living with HIV in Guangxi, China: An Observational Cohort Study.

Biomed Res Int 2021 10;2021:6657112. Epub 2021 Feb 10.

School of Public Health, Peking University, Beijing, China.

Objective: To assess the mortality and attrition rates within the first year of antiretroviral therapy (ART) initiation among people living with human immunodeficiency virus (PLHIV) in rural Guangxi, China.

Design: Observational cohort study. . The core treatment indicators and data were collected with standard and essential procedures as per the Free ART Manual guidelines across all the rural health care centers of Guangxi. . 58,115 PLHIV who were under ART were included in the study. . The data collected included sociodemographic characteristics that consist of age, sex, marital status, route of HIV transmission, CD4 cell count before ART, initial ART regimen, level of ART site, and year of ART initiation. . Mortality and attrition rate following ART initiation.

Results: The average mortality rate was 5.94 deaths, and 17.52 attritions per 100 person-years within the first year of ART initiation among PLHIV. The mortality rate was higher among intravenous drug users (Adjusted Hazard Ratio (AHR) 1.27, 95% Confidence Interval (CI) 1.14-1.43), prefecture as a level of ART site (AHR 1.14, 95% CI 1.02-1.28), and county as the level of ART site (AHR 2.12, 95% CI 1.90-2.37). Attrition was higher among intravenous drug users (AHR 1.87, 95% CI 1.75-2.00), the first-line ART containing AZT (AHR 1.09, 95% CI 1.03-1.16), and first-line ART containing LVP/r (AHR 1.34, 95% CI 1.23-1.46).

Conclusion: The mortality and attrition rates were both at the highest level in the first year of post-ART; continued improvement in the quality of HIV treatment and care is needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/6657112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892219PMC
May 2021

Development of an Oil-in-Water Self-Emulsifying Microemulsion for Cutaneous Delivery of Rose Bengal: Investigation of Anti-Melanoma Properties.

Pharmaceutics 2020 Oct 5;12(10). Epub 2020 Oct 5.

Therapeutics Research Group, University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia.

The topical delivery route is proposed as an alternative or adjunctive approach to melanoma treatment, since the target site for melanoma treatment-the epidermal basal layer-is potentially accessible by this route. Microemulsion systems are effective delivery vehicles for enhanced, targeted skin delivery. This work investigated the effect of Rose Bengal (RB) and RB-loaded self-emulsifying microemulsions (SEMEs) on growth inhibition of human melanoma and normal skin cell monolayers, the safety of the excipients incorporated in SEMEs on human cell lines, and the in-vitro human skin penetration of RB delivered in SEMEs and control solution. Cellular toxicity was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the growth inhibitory mechanism of RB was investigated by flow cytometry using PI staining. Unloaded SEMEs caused reduced cellular toxicity compared to the surfactant excipient, Labrasol. RB-loaded SEMEs increased cell growth inhibition compared to the RB aqueous solution. Flow cytometry revealed apoptotic cells after treatment with RB-loaded SEMEs, indicating that apoptosis may be one of the mechanisms of cell death. Preliminary results of multiphoton microscopy with fluorescence lifetime imaging (MPM-FLIM) analysis showed deeper penetration with greater skin concentrations of RB delivered from SEMEs compared to the RB aqueous solution. This study highlights the enhanced skin penetration and antimelanoma effects of RB loaded in a SEME system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pharmaceutics12100947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600403PMC
October 2020

Nanostructures Formed by Custom-Made Peptides Based on Amyloid Peptide Sequences and Their Inhibition by 2-Hydroxynaphthoquinone.

Front Chem 2020 6;8:684. Epub 2020 Aug 6.

Department of Chemistry and Earth Sciences, Qatar University, Doha, Qatar.

Extensive research on amyloid fibril formations shows that certain core sequences within Aβ peptide play an important role in their formation. It is impossible to track these events . Many proteins and peptides with such core sequences form amyloid fibrils and such Aβ sheet mimics have become excellent tools to study amyloid fibril formation and develop therapeutic strategies. A group of peptides based on amyloid peptide sequences obtained from PDB searches, where glycine residues are substituted with alanine and isoleucine, are tested for aggregation by SEM and ThT binding assay. SEM of different peptide sequences showed morphologically different structures such as nanorods, crystalline needles and nanofibrils. The peptides were co-incubated with HNQ (a quinone) to study its effect on the process of aggregation and/or fibrillation. In conclusion, this group of peptides seem to be Aβ sheet mimics and can be very useful in understanding the different morphologies of amyloid fibrils arising from different peptide sequences and the effective strategies to inhibit or anneal them.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fchem.2020.00684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424059PMC
August 2020

Using in vivo multiphoton fluorescence lifetime imaging to unravel disease-specific changes in the liver redox state.

Methods Appl Fluoresc 2020 Jul 7;8(3):034003. Epub 2020 Jul 7.

Therapeutics Research Group, University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD 4102, Australia.

Multiphoton fluorescence lifetime microscopy has revolutionized studies of pathophysiological and xenobiotic dynamics, enabling the spatial and temporal quantification of these processes in intact organs in vivo. We have previously used multiphoton fluorescence lifetime microscopy to characterise the morphology and amplitude weighted mean fluorescence lifetime of the endogenous fluorescent metabolic cofactor nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) of mouse livers in vivo following induction of various disease states. Here, we extend the characterisation of liver disease models by using nonlinear regression to estimate the unbound, bound fluorescence lifetimes for NAD(P)H, flavin adenine dinucleotide (FAD), along with metabolic ratios and examine the impact of using multiple segmentation methods. We found that NAD(P)H amplitude ratio, and fluorescence lifetime redox ratio can be used as discriminators of diseased liver from normal liver. The redox ratio provided a sensitive measure of the changes in hepatic fibrosis and biliary fibrosis. Hepatocellular carcinoma was associated with an increase in spatial heterogeneity and redox ratio coupled with a decrease in mean fluorescence lifetime. We conclude that multiphoton fluorescence lifetime microscopy parameters and metabolic ratios provided insights into the in vivo redox state of diseased compared to normal liver that were not apparent from a global, mean fluorescence lifetime measurement alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1088/2050-6120/ab93deDOI Listing
July 2020

Quality by Design: Development of the Quality Target Product Profile (QTPP) for Semisolid Topical Products.

Pharmaceutics 2020 Mar 23;12(3). Epub 2020 Mar 23.

Therapeutics Research Group, The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, Brisbane 4102, Australia.

In recent years, the "quality by design" (QbD) approach has been used for developing pharmaceutical formulations. This is particularly important for complex dosage forms such as topical semisolid products. The first step for developing a product using this efficient approach is defining the quality target product profile (QTPP), a list of quality attributes (QAs) that are required to be present in the final product. These quality attributes are affected by the ingredients used as well as manufacturing procedure parameters. Hence, critical material attributes (CMAs) and critical process parameters (CPPs) need to be specified. Possible failure modes of a topical semisolid product can be determined based on the physiochemical properties of ingredients and manufacturing procedures. In this review, we have defined and specified QTPP, QAs, CMAs and CPPs that are required for developing a topical semisolid product based on the QbD approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pharmaceutics12030287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150996PMC
March 2020

Advances and controversies in studying sunscreen delivery and toxicity.

Adv Drug Deliv Rev 2020 01 19;153:72-86. Epub 2020 Feb 19.

Future Industries Institute, University of South Australia, Adelaide, Australia. Electronic address:

This review critically evaluates the sunscreen delivery and toxicity field. We chose to focus on approved sunscreens in this review. Optimal sunscreen use prevents skin cancer and photoageing but there is an important knowledge gap in sunscreen/skin interactions. Sunscreen delivery is a key for efficacy, but studying sunscreen delivery is not straightforward. We review the strengths and weaknesses of in vitro, excised skin and clinical approaches. Understanding positive and negative sunscreen effects on skin homeostasis is also challenging. The results in this field, especially in vitro testing, are controversial and experimental design varies widely which further supports disparities between some findings. We hypothesize that bias towards showing sunscreen toxicity to increase impact could be problematic. We explore that perception through a detailed review of experimental design, especially in cell culture models. Our conclusion is that emerging, non- and minimally invasive technologies are enabling new approaches to volunteer studies that could significantly improve knowledge of sunscreen delivery and interactions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.addr.2020.02.001DOI Listing
January 2020

Novel Nanocarriers for Targeted Topical Skin Delivery of the Antioxidant Resveratrol.

Pharmaceutics 2020 Jan 29;12(2). Epub 2020 Jan 29.

School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6845, Australia.

Resveratrol (RSV) is a potent lipophilic antioxidant with a low aqueous solubility. Novel nanoformulations have been successfully developed and evaluated to increase the potential of resveratrol as a skin targeting antioxidant. Nanoformulations were prepared using a spontaneous emulsification method, and characterized and evaluated for their capabilities to penetrate/permeate the skin. In nanoformulations, the thermodynamic activity of the RSV penetration into/permeation through the skin was correlated with the thermodynamic activity of the RSV in the formulations. When terpenes were incorporated into the nanoformulations, the permeation of RSV through the skin increased and correlated with an increasing lipophilicity of the terpene. The nanoemulsion containing eugenol showed the highest RSV penetration into the stratum corneum (SC) and the epidermis-dermis-follicle region, whereas the limonene containing nanoemulsion had the highest RSV permeation through the skin (the enhancement ratios, compared to a saturated solution of RSV, were (i) 9.55 and (ii) 12.61, respectively, based on the average RSV amount (i) in each skin region and (ii) permeation through skin).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pharmaceutics12020108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076350PMC
January 2020

Bathing Does Not Facilitate Human Skin Penetration or Adverse Cellular Effects of Nanoparticulate Zinc Oxide Sunscreens after Topical Application.

J Invest Dermatol 2020 08 21;140(8):1656-1659. Epub 2020 Jan 21.

Therapeutics Research Centre, The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia; School of Pharmacy and Medical Sciences, University of South Australia, Sansom Institute, City East Campus, Adelaide, South Australia, Australia. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jid.2019.12.024DOI Listing
August 2020

Noninvasive in vivo human multiphoton microscopy: a key method in proving nanoparticulate zinc oxide sunscreen safety.

J Biomed Opt 2020 01;25(1):1-19

Diamantina Institute, The Univ. of Queensland, Australia.

We describe the contribution of our multiphoton microscopy (MPM) studies over the last ten years with DermaInspect (JenLab, Germany), a CE-certified medical tomograph based on detection of fluorescent biomolecules, to the assessment of possible penetration of nanoparticulate zinc oxide in sunscreen through human skin. At the time we started our work, there was a strong movement for the precautionary principle to be applied to the use of nanoparticles in consumer products due to a lack of knowledge. The combined application of different MPM modalities, including spectral imaging, fluorescence lifetime imaging, second harmonic fluorescence generation, and phosphorescence microscopy, has provided overwhelming evidence that nanoparticle zinc oxide particles do not penetrate human skin when applied to various skin types with a range of methods of topical sunscreen application. MPM has also been used to study the viable epidermal morphology and redox state in supporting the safe use of topical zinc oxide nanoparticles. The impact of this work is emphasized by the recent proposed rule by the United States FDA on Sunscreen Drug Products for Over-the-Counter Human Use, which listed only zinc oxide and titanium dioxide of the currently marketed products to be generally recognized as safe and effective.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1117/1.JBO.25.1.014509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008509PMC
January 2020

Mechanistic Evaluation of Enhanced Curcumin Delivery through Human Skin In Vitro from Optimised Nanoemulsion Formulations Fabricated with Different Penetration Enhancers.

Pharmaceutics 2019 Dec 1;11(12). Epub 2019 Dec 1.

Therapeutics Research Centre, University of Queensland Diamantina Institute, University of Queensland, 4102 Woolloongabba, QLD, Australia.

Curcumin is a natural product with chemopreventive and other properties that are potentially useful in treating skin diseases, including psoriasis and melanoma. However, because of the excellent barrier function of the stratum corneum and the relatively high lipophilicity of curcumin (log 3.6), skin delivery of curcumin is challenging. We used the principles of a Quality by Design (QbD) approach to develop nanoemulsion formulations containing biocompatible components, including Labrasol and Lecithin as surfactants and Transcutol and ethanol as cosurfactants, to enhance the skin delivery of curcumin. The nanoemulsions were characterised by cryo-SEM, Zeta potential, droplet size, pH, electrical conductivity (EC) and viscosity (). Physicochemical long-term stability (6 months) was also investigated. The mean droplet sizes as determined by dynamic light scattering (DLS) were in the lower submicron range (20-50 nm) and the average Zeta potential values were low (range: -0.12 to -2.98 mV). Newtonian flow was suggested for the nanoemulsions investigated, with dynamic viscosity of the nanoemulsion formulations ranging from 5.8 to 31 cP. The droplet size of curcumin loaded formulations remained largely constant over a 6-month storage period. The inclusion of terpenes to further enhance skin permeation was also examined. All nanoemulsions significantly enhanced the permeation of curcumin through heat-separated human epidermal membranes, with the greatest effect being a 28-fold increase in maximum flux () achieved with a limonene-based nanoemulsion, compared to a 60% ethanol in water control vehicle. The increases in curcumin flux were associated with increased skin diffusivity. In summary, we demonstrated the effectiveness of nanoemulsions for the skin delivery of the lipophilic active compound curcumin, and elucidated the mechanism of permeation enhancement. These formulations show promise as delivery vehicles for curcumin to target psoriasis and skin cancer, and more broadly for other skin delivery applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pharmaceutics11120639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956259PMC
December 2019

Investigation of Biochemical Alterations in Ischemic Stroke Using Fourier Transform Infrared Imaging Spectroscopy-A Preliminary Study.

Brain Sci 2019 Oct 25;9(11). Epub 2019 Oct 25.

Diabetes Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha 34110, Qatar.

Objective: Brain damage, long-term disability and death are the dreadful consequences of ischemic stroke. It causes imbalance in the biochemical constituents that distorts the brain dynamics. Understanding the sub-cellular alterations associated with the stroke will contribute to deeper molecular understanding of brain plasticity and recovery. Current routine approaches examining lipid and protein biochemical changes post stoke can be difficult. Fourier Transform Infrared (FTIR) imaging spectroscopy can play a vital role in detecting these molecular alterations on a sub-cellular level due to its high spatial resolution, accuracy and sensitivity. This study investigates the biochemical and molecular changes in peri-infract zone (PIZ) (contiguous area not completely damaged by stroke) and ipsi-lesional white matter (WM) (right below the stroke and PIZ regions) nine weeks post photothrombotic ischemic stroke in rats.

Materials And Methods: FTIR imaging spectroscopy and transmission electron microscopy (TEM) techniques were applied to investigate brain tissue samples while hematoxylin and eosin (H&E) stained images of adjacent sections were prepared for comparison and examination the morphological changes post stroke.

Results: TEM results revealed shearing of myelin sheaths and loss of cell membrane, structure and integrity after ischemic stroke. FTIR results showed that ipsi-lesional PIZ and WM experienced reduction in total protein and total lipid content compared to contra-lesional hemisphere. The lipid/protein ratio reduced in PIZ and adjacent WM indicated lipid peroxidation, which results in lipid chain fragmentation and an increase in olefinic content. Protein structural change is observed in PIZ due to the shift from random coli and α-helical structures to β-sheet conformation.

Conclusion: FTIR imaging bio-spectroscopy provide novel biochemical information at sub-cellular levels that be difficult to be obtained by routine approaches. The results suggest that successful therapeutic strategy that is based on administration of anti-oxidant therapy, which could reduce and prevent neurotoxicity by scavenging the lipid peroxidation products. This approach will mitigate tissue damage in chronic ischemic period. FTIR imaging bio-spectroscopy can be used as a powerful tool and offer new approach in stroke and neurodegenerative diseases research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/brainsci9110293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895834PMC
October 2019

Targeted Topical Delivery of Retinoids in the Management of Acne Vulgaris: Current Formulations and Novel Delivery Systems.

Pharmaceutics 2019 Sep 24;11(10). Epub 2019 Sep 24.

School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth 6845, Australia.

Acne vulgaris is a common inflammatory pilosebaceous condition that affects 80-90% of adolescents. Since the introduction of tretinoin over 40 years ago, topical retinoid products have been a mainstay of acne treatment. The retinoids are very effective in addressing multiple aspects of the acne pathology as they are comedolytic and anti-inflammatory, and do not contribute to antibiotic resistance or microbiome disturbance that can be associated with long-term antibiotic therapies that are a common alternative treatment. However, topical retinoids are associated with skin dryness, erythema and pain, and may exacerbate dermatitis or eczema. Thus, there is a clear need to target delivery of the retinoids to the pilosebaceous units to increase efficacy and minimise side effects in surrounding skin tissue. This paper reviews the current marketed topical retinoid products and the research that has been applied to the development of targeted topical delivery systems of retinoids for acne.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pharmaceutics11100490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835300PMC
September 2019

Cellular metabolism and pore lifetime of human skin following microprojection array mediation.

J Control Release 2019 07 21;306:59-68. Epub 2019 May 21.

Therapeutics Research Centre, Faculty of Medicine, The University of Queensland, Translational Research Institute, Woolloongabba, QLD 4102, Australia; School of Pharmacy and Medical Sciences, University of South Australia, Basil Hetzel Institute for Translational Health Research, Adelaide, SA 5011, Australia. Electronic address:

Skin-targeting microscale medical devices are becoming popular for therapeutic delivery and diagnosis. We used cryo-SEM, fluorescence lifetime imaging microscopy (FLIM), autofluorescence imaging microscopy and inflammatory response to study the puncturing and recovery of human skin ex vivo and in vivo after discretised puncturing by a microneedle array (Nanopatch®). Pores induced by the microprojections were found to close by ~25% in diameter within the first 30 min, and almost completely close by ~6 h. FLIM images of ex vivo viable epidermis showed a stable fluorescence lifetime for unpatched areas of ~1000 ps up to 24 h. Only the cells in the immediate puncture zones (in direct contact with projections) showed a reduction in the observed fluorescence lifetimes to between ~518-583 ps. The ratio of free-bound NAD(P)H (α1/α2) in unaffected areas of the viable epidermis was ~2.5-3.0, whereas the ratio at puncture holes was almost double at ~4.2-4.6. An exploratory pilot in vivo study also suggested similar closure rate with histamine administration to the forearms of human volunteers after Nanopatch® treatment, although a prolonged inflammation was observed with Tissue Viability Imaging. Overall, this work shows that the pores created by the microneedle-type medical device, Nanopatch®, are transient, with the skin recovering rapidly within 1-2 days in the epidermis after application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jconrel.2019.05.024DOI Listing
July 2019

Evaluation of Quantum Dot Skin Penetration in Porcine Skin: Effect of Age and Anatomical Site of Topical Application.

Skin Pharmacol Physiol 2019 14;32(4):182-191. Epub 2019 May 14.

School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Bentley, Washington, Australia,

Background: Pig skin is a widely acknowledged surrogate for human skin for in vitro/ex vivo skin penetration studies with application for small molecules and nanosystems. We have investigated the influence of biological factors such as age and anatomical site on the penetration and distribution of nanoparticles (2.1 nm hydrophilic CdTe/CdS quantum dots: QDs) in adult pig skin (APS), weanling pig skin (WPS) and newborn pig skin (NBPS) at two different anatomical sites (ear and abdomen).

Methods: QDs in saline were applied to 1 × 1 cm2 skin (62.5 pmol/cm2) with 2-min finger rubbing using a standardized protocol. After 6- or 24-h incubation on Franz diffusion cells, tape stripping (×10) followed by manual follicular casting was conducted. Cadmium in QDs was quantified using inductively coupled plasma mass spectrometry for all samples. The presence of QDs in similarly treated skin samples was also captured using multiphoton tomography.

Results: QDs were mainly localized in hair follicles after 6 and 24 h of exposure with no cadmium detected in the Franz cell receptor compartment regardless of pig age or anatomical site. The amount of QDs deposited in the follicles was similar at 6 h but higher on APS and WPS ears compared to NBPS ears at 24 h. This is associated with the high follicle density and small follicle diameter of the NBPS compared to the smaller density of much larger follicles on the APS. NBPS showed consistent QD distribution for ear and abdomen up to 24 h.

Conclusions: There is minimal penetration of QDs through pig skin. Density and diameter of follicles in association with age of pigs and application site influenced the amount of QDs deposited in follicles. The structure of the stratum corneum, follicle density and diameter of NBPS are similar to human skin suggesting that NBPS is an appropriate model for human skin in the evaluation of topical applications of a range of chemicals including nanosystems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000499435DOI Listing
January 2020

Permeation Mechanism of Caffeine and Naproxen through in vitro Human Epidermis: Effect of Vehicles and Penetration Enhancers.

Skin Pharmacol Physiol 2019 25;32(3):132-141. Epub 2019 Mar 25.

Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, Queensland, Australia,

Background/aims: The mechanisms by which permeation enhancers increase human skin permeation of caffeine and naproxen were assessed in vitro.

Methods: Active compound solubility in the vehicles and in the stratum corneum (SC), active compound flux across epidermal membranes and uptake of active and vehicle components into the SC were measured. The effect of vehicle pH on the permeation of caffeine and naproxen was also determined.

Results: Oleic acid and eucalyptol significantly enhanced the skin penetration of caffeine and naproxen, compared to aqueous controls. Naproxen permeation was increased from vehicles with pH presenting more ionized naproxen. Caffeine maximum flux enhancement was associated with an increase in caffeine SC solubility and skin diffusivity, whereas for naproxen a penetration enhancer/vehicle-induced increase in solubility in the SC correlated with an increase in maximum flux. SC solubility was related to experimentally determined active uptake, which was in turn predicted by vehicle uptake and active compound solubility in the vehicle.

Conclusion: A permeation enhancer-induced alteration in diffusivity, rather than effects on SC solubility, was the main driving force behind increases in permeation flux of the hydrophilic molecule caffeine. For the more the lipophilic molecule naproxen, increased SC solubility drove the increases in permeation flux.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000497225DOI Listing
November 2019

Optical Characterization of Zinc Pyrithione.

Photochem Photobiol 2019 09 22;95(5):1142-1150. Epub 2019 Apr 22.

School of Pharmacy and Medical Sciences, University of South Australia and Basil Hetzel Institute for Translational Health Research, Adelaide, SA, Australia.

Zinc pyrithione is ubiquitous in commercial products particularly antidandruff shampoos. For the efficacy of zinc pyrithione therapeutic cleansers to be assessed accurately, the distribution of particles on the scalp needs to be visualized. Currently, no technique is available which provides the chemical specificity and sensitivity required. Here, we report application of fluorescence-lifetime imaging microscopy (FLIM) for high-contrast mapping of zinc pyrithione distribution on the scalp. Characterization of the zinc pyrithione emission by using both one-photon excitation at five specific wavelengths and two-photon excitation in the range of 740-820 nm revealed its FLIM fingerprint-a characteristic short average time-weighted emission lifetime of Τ = 250 ps. Bandpass-filtering FLIM signals at Τ enabled an efficient discrimination between the zinc pyrithione and major endogenous skin species in comparison with that of the conventional reflectance confocal microscopy. Our findings provide means for in vivo high-sensitivity assaying and high-contrast imaging of zinc pyrithione in biological systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/php.13100DOI Listing
September 2019

Vision-based Mobile Indoor Assistive Navigation Aid for Blind People.

IEEE Trans Mob Comput 2019 Mar 1;18(3):702-714. Epub 2018 Jun 1.

Federal Highway Administration, Washington, DC 20590, USA.

This paper presents a new holistic vision-based mobile assistive navigation system to help blind and visually impaired people with indoor independent travel. The system detects dynamic obstacles and adjusts path planning in real-time to improve navigation safety. First, we develop an indoor map editor to parse geometric information from architectural models and generate a semantic map consisting of a global 2D traversable grid map layer and context-aware layers. By leveraging the visual positioning service (VPS) within the Google Tango device, we design a map alignment algorithm to bridge the visual area description file (ADF) and semantic map to achieve semantic localization. Using the on-board RGB-D camera, we develop an efficient obstacle detection and avoidance approach based on a time-stamped map Kalman filter (TSM-KF) algorithm. A multi-modal human-machine interface (HMI) is designed with speech-audio interaction and robust haptic interaction through an electronic SmartCane. Finally, field experiments by blindfolded and blind subjects demonstrate that the proposed system provides an effective tool to help blind individuals with indoor navigation and wayfinding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TMC.2018.2842751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371975PMC
March 2019

Topical and Transdermal Drug Delivery: From Simple Potions to Smart Technologies.

Curr Drug Deliv 2019 ;16(5):444-460

Diamantina Institute, The University of Queensland, Translational Research Institute, QLD, 4102, Australia.

This overview on skin delivery considers the evolution of the principles of percutaneous absorption and skin products from ancient times to today. Over the ages, it has been recognised that products may be applied to the skin for either local or systemic effects. As our understanding of the anatomy and physiology of the skin has improved, this has facilitated the development of technologies to effectively and quantitatively deliver solutes across this barrier to specific target sites in the skin and beyond. We focus on these technologies and their role in skin delivery today and in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1567201816666190201143457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637104PMC
November 2019

Space- and time-resolved investigation on diffusion kinetics of human skin following macromolecule delivery by microneedle arrays.

Sci Rep 2018 12 10;8(1):17759. Epub 2018 Dec 10.

Australian National University, Canberra, ACT, 0200, Australia.

Microscale medical devices are being developed for targeted skin delivery of vaccines and the extraction of biomarkers, with the potential to revolutionise healthcare in both developing and developed countries. The effective clinical development of these devices is dependent on understanding the macro-molecular diffusion properties of skin. We hypothesised that diffusion varied according to specific skin layers. Using three different molecular weights of rhodamine dextran (RD) (MW of 70, 500 and 2000 kDa) relevant to the vaccine and therapeutic scales, we deposited molecules to a range of depths (0-300 µm) in ex vivo human skin using the Nanopatch device. We observed significant dissipation of RD as diffusion with 70 and 500 kDa within the 30 min timeframe, which varied with MW and skin layer. Using multiphoton microscopy, image analysis and a Fick's law analysis with 2D cartesian and axisymmetric cylindrical coordinates, we reported experimental trends of epidermal and dermal diffusivity values ranging from 1-8 µm s to 1-20 µm s respectively, with a significant decrease in the dermal-epidermal junction of 0.7-3 µm s. In breaching the stratum corneum (SC) and dermal-epidermal junction barriers, we have demonstrated practical application, delivery and targeting of macromolecules to both epidermal and dermal antigen presenting cells, providing a sound knowledge base for future development of skin-targeting clinical technologies in humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-36009-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288161PMC
December 2018

Support for the Safe Use of Zinc Oxide Nanoparticle Sunscreens: Lack of Skin Penetration or Cellular Toxicity after Repeated Application in Volunteers.

J Invest Dermatol 2019 02 15;139(2):308-315. Epub 2018 Nov 15.

Therapeutics Research Centre, The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia; School of Pharmacy and Medical Sciences, University of South Australia, Sansom Institute, City East Campus, Adelaide, Australia. Electronic address:

Zinc oxide is a widely used broad-spectrum sunscreen, but concerns have been raised about the safety of its nanoparticle (NP) form. We studied the safety of repeated application of agglomerated zinc oxide (ZnO) NPs applied to human volunteers over 5 days by assessing the skin penetration of intact ZnO-NPs and zinc ions and measuring local skin toxicity. Multiphoton tomography with fluorescence lifetime imaging microscopy was used to directly visualize ZnO-NP skin penetration and viable epidermal metabolic changes in human volunteers. The fate of ZnO-NPs was also characterized in excised human skin in vitro. ZnO-NPs accumulated on the skin surface and within the skin furrows but did not enter or cause cellular toxicity in the viable epidermis. Zinc ion concentrations in the viable epidermis of excised human skin were slightly elevated. In conclusion, repeated application of ZnO-NPs to the skin, as used in global sunscreen products, appears to be safe, with no evidence of ZnO-NP penetration into the viable epidermis nor toxicity in the underlying viable epidermis. It was associated with the release and penetration of zinc ions into the skin, but this did not appear to cause local toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jid.2018.08.024DOI Listing
February 2019

Using elongated microparticles to enhance tailorable nanoemulsion delivery in excised human skin and volunteers.

J Control Release 2018 10 15;288:264-276. Epub 2018 Sep 15.

Future Industries Institute, University of South Australia, Adelaide, Australia; Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute at the Princess Alexandra Hospital, Brisbane, Australia. Electronic address:

This study demonstrates, for the first time, clinical testing of elongated silica microparticles (EMP) combined with tailorable nanoemulsions (TNE) to enhance topical delivery of hydrophobic drug surrogates. Likewise, this is the first report of 6-carboxyfluorescein (a model molecule for topically delivered hydrophobic drugs) AM1 & DAMP4 (novel short peptide surfactants) used in volunteers. The EMP penetrates through the epidermis and stop at the dermal-epidermal junction (DEJ). TNE are unusually stable and useful because the oil core allows high drug loading levels and the surface properties can be easily controlled. At first, we chose alginate as a crosslinking agent between EMP and TNE. We initially incorporated a fluorescent lipophilic dye, DiI, as a hydrophobic drug surrogate into TNE for visualization with microscopy. We compared four different coating approaches to combine EMP and TNE and tested these formulations in freshly excised human skin. The delivery profile characterisation was imaged by dye- free coherent anti-Stoke Raman scattering (CARS) microscopy to detect the core droplet of TNE that was packed with pharmaceutical grade lipid (glycerol) instead of DiI. These data show the EMP penetrating to the DEJ followed by controlled release of the TNE. Freeze-dried formulations with crosslinking resulted in a sustained release profile, whereas a freeze-dried formulation without crosslinking showed an immediate burst-type release profile. Finally, we tested the crosslinked TNE coated EMP formulation in volunteers using multiphoton microscopy (MPM) and fluorescence-lifetime imaging microscopy (FLIM) to document the penetration depth characteristics. These forms of microscopy have limitations in terms of image acquisition speed and imaging area coverage but can detect fluorescent drug delivery through the superficial skin in volunteers. 6-Carboxyfluorescein was selected as the fluorescent drug surrogate for the volunteer study based on the similarity of size, charge and hydrophobicity characteristics to small therapeutic drugs that are difficult to deliver through skin. The imaging data showed a 6-carboxyfluorescein signal deep in volunteer skin supporting the hypothesis that EMP can indeed enhance the delivery of TNE in human skin. There were no adverse events recorded at the time of the study or after the study, supporting the use of 6-carboxyfluorescein as a safe and detectable drug surrogate for topical drug research. In conclusion, dry formulations, with controllable release profiles can be obtained with TNE coated EMP that can effectively enhance hydrophobic payload delivery deep into the human epidermis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jconrel.2018.09.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050638PMC
October 2018

Removing physiological motion from intravital and clinical functional imaging data.

Elife 2018 07 9;7. Epub 2018 Jul 9.

Kinghorn Cancer Centre, Garvan Institute of Medical Research, University of New South Wales, Sydney, Australia.

Intravital microscopy can provide unique insights into the function of biological processes in a native context. However, physiological motion caused by peristalsis, respiration and the heartbeat can present a significant challenge, particularly for functional readouts such as fluorescence lifetime imaging (FLIM), which require longer acquisition times to obtain a quantitative readout. Here, we present and benchmark , a versatile multi-platform software tool for image-based correction of sample motion blurring in both time resolved and conventional laser scanning fluorescence microscopy data in two and three dimensions. We show that is able to resolve intravital FLIM-FRET images of intra-abdominal organs in murine models and NADH autofluorescence of human dermal tissue imaging subject to a wide range of physiological motions. Thus, can enable FLIM imaging in situations where a stable imaging platform is not always possible and rescue previously discarded quantitative imaging data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.35800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6037484PMC
July 2018

HIV, syphilis and behavioral risk factors among men who have sex with men in a drug-using area of southwestern China: Results of 3 cross-sectional surveys from 2013 to 2015.

Medicine (Baltimore) 2018 Apr;97(16):e0404

Guangxi Center for Disease Control and Prevention, Nanning State Key Laboratory for Infectious Disease Prevention and Control (SKLID), Chinese Center for Disease Control and Prevention (China CDC), Beijing Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China Department of Public Health, Western Kentucky University, Bowling Green, KY Department of Health Services Administration, Florida International University, Miami, FL.

To assess human immunodeficiency virus (HIV), syphilis, and behavioral risk factors among men who have sex with men (MSM) in southwestern China, where HIV started as a drug-driven epidemic, and shifted to mainly heterosexual transmission.These cross-sectional studies were conducted yearly in 2013, 2014, and 2015 in Guangxi, China. A total of 1,996, 1,965, and 1,697 participants were recruited in 2013, 2014, and 2015, respectively. The data included demographic and sexual behavioral variables. Other variables included individuals who used illegal drugs, and who received HIV counseling, testing, and free condoms, and peer education. Participants were tested for HIV, syphilis, and hepatitis C virus (HCV) with whole blood specimens. Questionnaires and laboratory testing data were double entered, and validated with EpiData software. The data were then transferred into SPSS software (SPSS Inc, Chicago, IL) and Chi-square test performed.The prevalence of HIV was 6.6% in 2013, 8.4% in 2014, and 11.2% in 2015. The prevalence of syphilis was 9.3% in 2013, 9.8% in 2014, and 6.1% in 2015. And HCV prevalence was 0.5% in 2013 and remained stable at 0.4% in 2014, and 2015. HIV infection, and associated factors among MSM in these 3 annual cross-sectional survey showed that HIV-infected MSM were significantly, more likely, to perform unprotected anal intercourse with any commercial male partners in the past 6 months (adjusted odds ratio [AOR] = 1.81, 95% CI: 1.50-2.20), had sex with any female partners in the past 6 months (AOR = 1.31, 95% CI: 1.01-1.71), used drugs in the past (AOR = 2.73, 95% CI: 1.30-5.71), and are syphilis infected (AOR = 3.53, 95% CI: 2.77-4.49).There is an urgent need for intervention strategies like condom distribution, HIV counseling, free testing, and education regarding safe sex, HIV, and other sex-related diseases in Guangxi to curb, and prevent HIV among MSM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000010404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916656PMC
April 2018

Using a simple equation to predict the microporation-enhanced transdermal drug flux.

Eur J Pharm Biopharm 2018 Jun 1;127:12-18. Epub 2018 Feb 1.

School of Natural Sciences, Griffith University, Gold Coast, Queensland 4222, Australia; Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Trubetskaya 8, 119991 Moscow, Russia. Electronic address:

The mathematical model describing drug flux through microporated skin was previously developed. Based on this model, two mathematical equations can be used to predict the microporatio-enhanced transdermal drug flux: the complex primal equation containing a variety of experimentally-determined variables, and the simplified straightforward equation. In this study, experimental transdermal fluxes of three corticosteroids through split-thickness human skin treated with a microneedle roller were measured, and the values of fluxes compared with those predicted using both the more complex and simplified equations. According to the results of the study, both equations demonstrated high accuracy in the prediction of the fluxes of corticosteroids. The simplified equation was validated and confirmed as robust using regression analysis of literature data. Further, its capability and ease of use was exemplified by predicting the flux of methotrexate through the skin microporated with laser and comparing with published experimental data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejpb.2018.01.019DOI Listing
June 2018

Cationic folate-mediated liposomal delivery of bis-arylidene oxindole induces efficient melanoma tumor regression.

Biomater Sci 2017 Aug;5(9):1898-1909

Chemical Biology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.

The folate receptor (FR) is a well-validated and common target for cancer due to its high over-expression in many different cancer cells. Herein, we developed a new FR-targeting ligand (FA8) by conjugating folic acid and a cationic lipid. Owing to its favorable structural property FA8 as a ligand could be accommodated at an unusually higher molar ratio for a ligand-targeted liposome. We then encapsulated a drug-like molecule, bis-arylidene oxindole (NME2), in the targeted liposome. The resulting formulation induced potent caspase-8 up-regulation even in FR-moderately expressing melanoma cells. The NME2-associated non-targeted liposome (i.e., without FA8) or pristine NME2 could not up-regulate caspase-8. Caspase-8, an important apoptotic protein involved in the extrinsic pathway of apoptosis-signalling and inhibition of acquired drug resistance, was induced in cancer cells due to the combination treatment of liposomally associated FA8 and NME2 through the activation and subsequent cleavage of RIP-1. Consistently, in a melanoma tumor model too wherein FR is moderately expressed, significant tumour regression was obtained with this liposomal combination of FA8 and NME2. In conclusion, we demonstrate the development of a new FR-targeting ligand molecule whose higher level of inclusion (>10 mol%) in the liposomal formulation altered the mode of anticancer action of the encapsulated drug, thereby indicating a new therapeutic possibility involving FR targeted cancer treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c7bm00405bDOI Listing
August 2017

Skin models for the testing of transdermal drugs.

Clin Pharmacol 2016 19;8:163-176. Epub 2016 Oct 19.

Translational Research Institute, School of Medicine, University of Queensland, Brisbane; School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia.

The assessment of percutaneous permeation of molecules is a key step in the evaluation of dermal or transdermal delivery systems. If the drugs are intended for delivery to humans, the most appropriate setting in which to do the assessment is the in vivo human. However, this may not be possible for ethical, practical, or economic reasons, particularly in the early phases of development. It is thus necessary to find alternative methods using accessible and reproducible surrogates for in vivo human skin. A range of models has been developed, including ex vivo human skin, usually obtained from cadavers or plastic surgery patients, ex vivo animal skin, and artificial or reconstructed skin models. Increasingly, largely driven by regulatory authorities and industry, there is a focus on developing standardized techniques and protocols. With this comes the need to demonstrate that the surrogate models produce results that correlate with those from in vivo human studies and that they can be used to show bioequivalence of different topical products. This review discusses the alternative skin models that have been developed as surrogates for normal and diseased skin and examines the concepts of using model systems for in vitro-in vivo correlation and the demonstration of bioequivalence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CPAA.S64788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5076797PMC
October 2016

A unique iridium(III) complex-based chemosensor for multi-signal detection and multi-channel imaging of hypochlorous acid in liver injury.

Biosens Bioelectron 2017 Jan 20;87:1005-1011. Epub 2016 Sep 20.

State Key Laboratory of Fine Chemicals, School of Chemistry, Dalian University of Technology, Dalian 116024, PR China.

Although hypochlorous acid (HOCl) has long been associated with a number of inflammatory diseases in mammalian bodies, the functions of HOCl in specific organs at abnormal conditions, such as liver injury, remain unclear due to its high reactivity and the lack of effective methods for its detection. Herein, a unique Ir(III) complex-based chemosensor, Ir-Fc, was developed for highly sensitive and selective detection of HOCl. Ir-Fc was designed by incorporating a ferrocene (Fc) quencher to a Ir(III) complex through a HOCl-responsive linker. In the presence of HOCl, the fast cleavage of Fc moiety in less than 1s led to the enhancement of photoluminescence (PL) and electrochemical luminescence (ECL), by which the concentration of HOCl was determined by both PL and ECL analysis. Taking advantages of excellent properties of Ir(III) complexes, optical and electrochemical analyses of the response of Ir-Fc towards HOCl were fully investigated. Followed by the measurements of low cytotoxicity of Ir-Fc by MTT analysis, one-photon (OP), two-photon (TP) and lifetime imaging experiments were conducted to visualise the generation of HOCl in live microphage and HepG2 cells, and in zebrafish and mouse, respectively. Furthermore, the generation and distribution of HOCl in liver cells and liver injury of zebrafish and mouse were investigated. The results demonstrated the applicability of Ir-Fc as an effective chemosensor for imaging of HOCl generation in mitochondria of cells and liver injury in vivo, implying the potential of Ir-Fc for biomedical diagnosis and monitoring applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bios.2016.09.067DOI Listing
January 2017

Mechanistic Evaluation of Hydration Effects on the Human Epidermal Permeation of Salicylate Esters.

AAPS J 2017 01 15;19(1):180-190. Epub 2016 Sep 15.

Therapeutics Research Centre, School of Medicine, University of Queensland, Translational Research Institute, Brisbane, Australia.

We sought to understand when and how hydration enhances the percutaneous absorption of salicylate esters. Human epidermal membrane fluxes and stratum corneum solubilities of neat and diluted solutions of three esters were determined under hydrated and dehydrated conditions. Hydration doubled the human epidermal flux seen for methyl and ethyl salicylate under dehydrated conditions and increased the flux of neat glycol salicylate 10-fold. Mechanistic analyses showed that this hydration-induced enhancement arises mainly from an increase in the stratum corneum diffusivity of the three esters. Further, we showed that unlike methyl and ethyl salicylate, glycol salicylate is hygroscopic and the ∼10-fold hydration-induced flux enhancement seen with neat glycol salicylate may be due to its ability to hydrate the stratum corneum to a greater extent. The hydration-induced enhancements in in vitro epidermal flux seen here for glycol and ethyl salicylate were similar to those reported for their percutaneous absorption rates in a comparable in vivo study, whilst somewhat higher enhancement was seen for methyl salicylate in vivo. This may be explained by a physiologically induced self enhancement of neat methyl salicylate absorption in vivo which is not applicable in vitro.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1208/s12248-016-9984-0DOI Listing
January 2017

Permeation of topically applied Magnesium ions through human skin is facilitated by hair follicles.

Magnes Res 2016 Jun;29(2):35-42

School of Chemistry and Molecular Biosciences, Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, 4072 Australia.

Magnesium is an important micronutrient essential for various biological processes and its deficiency has been linked to several inflammatory disorders in humans. Topical magnesium delivery is one of the oldest forms of therapy for skin diseases, for example Dead Sea therapy and Epsom salt baths. Some anecdotal evidence and a few published reports have attributed amelioration of inflammatory skin conditions to the topical application of magnesium. On the other hand, transport of magnesium ions across the protective barrier of skin, the stratum corneum, is contentious. Our primary aim in this study was to estimate the extent of magnesium ion permeation through human skin and the role of hair follicles in facilitating the permeation. Upon topical application of magnesium solution, we found that magnesium penetrates through human stratum corneum and it depends on concentration and time of exposure. We also found that hair follicles make a significant contribution to magnesium penetration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1684/mrh.2016.0402DOI Listing
June 2016
-->