Evaluating the effects of giraffe skin disease and wire snare wounds on the gaits of free-ranging Nubian giraffe.

Giraffe skin disease (GSD), a condition that results in superficial lesions in certain giraffe (Giraffa spp.) populations, has emerged as a potential conservation threat. Preliminary findings suggested that individuals with GSD lesions move with greater difficulty which may in turn reduce their foraging efficiency or make them more vulnerable to predation. A current known threat to some giraffe populations is their mortality associated with entrapment in wire snares, and the morbidity and potential locomotor deficiencies associated with wounds acquired from snares. The goal of our study was to quantify the locomotor kinematics of free-ranging Nubian giraffe (G. camelopardalis camelopardalis) in Murchison Falls National Park (MFNP), Uganda, and compare spatiotemporal limb and neck angle kinematics of healthy giraffe to those of giraffe with GSD lesions, snare wounds, and both GSD lesions and snare wounds. The presence of GSD lesions did not significantly affect spatiotemporal limb kinematic parameters. This finding is potentially because lesions were located primarily on the necks of Nubian giraffe in MFNP. The kinematic parameters of individuals with snare wounds differed from those of healthy individuals, resulting in significantly shorter stride lengths, reduced speed, lower limb phase values, and increased gait asymmetry. Neck angle kinematic parameters did not differ among giraffe categories, which suggests that GSD neck lesions do not impair normal neck movements and range of motion during walking. Overall, MFNP giraffe locomotor patterns are largely conservative between healthy individuals and those with GSD, while individuals with snare wounds showed more discernible kinematic adjustments consistent with unilateral limb injuries. Additional studies are recommended to assess spatiotemporal limb kinematics of giraffe at sites where lesions are found predominantly on the limbs to better assess the potential significance of GSD on their locomotion.

The effect of dilution of fusidic acid cream and betamethasone dipropionate cream in complex extemporaneous mixes on formulation performance.

The Aron regimen is an unconventional therapy which entails frequent applications of an extemporaneously prepared three component system (a topical antibiotic, a corticosteroid and an emollient), with the intention of decolonising the skin of S. aureus whilst treating atopic dermatitis. The impact of heavily diluting these topical medicinal products, to differing extents, on formulation performance is not well understood thus was investigated in this study. Following a single application of a range of compounded Aron mixes (fusidic acid and betamethasone dipropionate diluted to varying extents in an emollient base), significant reductions in the expected drug flux across silicone membrane, ex vivo percutaneous absorption and skin retention of both drugs relative to the marketed products were observed. This was attributed to a number of complex formulation effects making such changes difficult to predict in a clinical setting. Further investigations are required to evaluate the impact of frequent applications of the Aron mix to widespread areas on clinical efficacy, antimicrobial resistance and long term side effects.

Correction to: Enhanced Follicular Delivery of Finasteride to Human Scalp Skin Using Heat and Chemical Penetration Enhancers.

The article Enhanced Follicular Delivery of Finasteride to Human Scalp Skin Using Heat and Chemical Penetration Enhancers, written by Farah, Brown, and McAuley was originally published electronically on the publisher's internet portal on 31 May, 2020 without open access.

Enhanced Follicular Delivery of Finasteride to Human Scalp Skin Using Heat and Chemical Penetration Enhancers.

PURPOSE: The aim of this work was to evaluate whether improved topical delivery of finasteride, focussed to the hair follicles of human scalp skin could be achieved with application of short durations of heat and use of specific chemical penetration enhancers. METHODS: Franz cell experiments with human scalp skin were performed with a range of chemical penetration enhancers at 32°C and 45°C to simulate normal and heated conditions. Selected chemical penetration enhancers were taken forward for finite dose Franz cell studies which examined the effect of heat produced by a prototype external heating system that supplied either 20 or 30 min of additional heat over both a 24 h and a 1 h time period. RESULTS: Short durations of externally applied heat significantly increased finasteride penetration into human scalp skin after 24 h. Analysis of drug distribution in the skin after 1 h and 24 h indicated that both heat and chemical penetration enhancer selection influenced drug delivery to the hair follicles. CONCLUSION: The use of short durations of heat in combination with specific chemical penetration enhancers was able to increase the delivery of finasteride to human scalp skin and provide focussed drug delivery to the hair follicles.

Prenatal infection with Mycoplasma pulmonis in rats exaggerates the angiotensin II pressor response in adult offspring.

Exposure to different stressors in utero is linked to adult diseases such as obesity and hypertension. In this study, the impact of prenatal infection (PNI) on adult body weight and cardiovascular function was evaluated using a naturally occurring rodent pathogen, Mycoplasma pulmonis (MP). Pregnant Sprague-Dawley rats were infected with MP on gestationalday 14 and gave birth naturally. Adult PNI offspring weighed more than controls, but resting mean arterial pressure (MAP) was unchanged. Subcutaneous injection of angiotensin II (10 µg/kg) elicited a rise in MAP that was greater in both male and female PNI offspring compared with controls (P < 0.03). The accompanying reflex bradycardia was similar to the controls, suggesting that PNI induced baroreflex dysfunction. Subcutaneous nicotine administration, a potent cardiorespiratory stimulus, also elicited a transient rise in MAP that was generally greater in the PNI group, but the change in MAP from baseline was only significant in the PNI females compared with controls (P < 0.03). Elevated body weight and cardiovascular reactivity in the PNI offspring was associated with an increase in the ratio of hypothalamic corticotrophin-releasing hormone receptors type 1 to type 2 gene expression in both sexes compared with controls. These findings support previous studies demonstrating that PNI induces alterations in cardiovascular function and body weight. Yet, unlike previous studies utilizing other models of PNI (e.g., endotoxin), MP PNI did not induce resting hypertension. Thus, our study provides a foundation for future studies evaluating the cardiovascular risks of offspring exposed to microbial challenges in utero.

Heat Enhanced Follicular Delivery of Isotretinoin to the Skin.

PURPOSE: The aim of this work was to evaluate the use of short durations of externally applied heat with chemical penetration enhancers to improve delivery of isotretinoin to the skin and in particular via the follicular route. METHODS: A range of chemical penetration enhancers were screened for their ability to improve isotretinoin delivery into human skin with heat using infinite dose, Franz cell experiments conducted in a water bath at a higher temperature to simulate heated conditions. Following this a prototype external heating system was developed that provided short durations of heat and its ability to improve delivery of finite doses into the skin and hair follicles was assessed. RESULTS: The magnitude of the effect of heat on drug delivery was influenced by the choice of vehicle with changes in isotretinoin flux across skin ranging from not statistically significant to 25 fold increases with heat in the infinite dose studies. The prototype heating system provided significant increases in the total delivery of isotretinoin into the skin from an optimised vehicle. Drug distribution in the skin revealed significant increases in isotretinoin delivery to the hair follicles, and deeper skin layers, but not to the stratum corneum, providing strong evidence that the enhancement in delivery occurred mainly via the hair follicles. CONCLUSION: These data indicate that the use of short durations of heat combined with chemical penetration enhancers offers a valuable strategy for improving the delivery of drugs such as isotretinoin to the skin via the hair follicles. Graphical Abstract Schematic illustration of the sodium thiosulphate heating system on a Franz diffusion cell and the subsequent impact of a short burst of heat on the delivery of isotretinoin into human skin.

The use of heat and chemical penetration enhancers to increase the follicular delivery of erythromycin to the skin.

The effect of heat on the follicular absorption of drugs into the skin has not previously been investigated. In comparison to drug delivery across the continuous stratum corneum (SC), follicular absorption is known to be relatively rapid and therefore the use of short durations of heat may be particularly useful for enhancing drug delivery to the hair follicles, as well as being practical for patients to use. In this study erythromycin has been used as a model drug and the combined use of heat and chemical penetration enhancers was found to be able to synergistically increase the penetration of erythromycin into human skin via the follicular route. Moreover durations of heat application as short as 10 min in combination with particular enhancer systems were found to be sufficient to significantly increase erythromycin delivery to the skin. Overall the data indicate that the use of heat with chemical penetration enhancers offers a potentially valuable strategy for delivering drugs via the follicular route.

Correction to: Factors associated with short interpregnancy interval among women treated with in vitro fertilization.

The original version of this article unfortunately contained a mistake. The name of an investigator was incorrectly listed as M. B. Morton, instead of M. B. Brown.

Factors associated with short interpregnancy interval among women treated with in vitro fertilization.

PURPOSE: To evaluate factors associated with interpregnancy interval (IPI) among women treated with in vitro fertilization (IVF). METHODS: Women with at least two cycles of IVF between 2004 and 2013 were identified from the SART CORS database and grouped by age at first cycle, infertility diagnosis, IVF treatment parameters, and cycle 1 outcome (singleton or multiple live birth or no live birth, length of gestation, and birthweight). The distributions of IPIs (in months, 0-5, 6-11, 12-17, 18-23, and ≥ 24) were compared across these factors. IPI was fit as a function of these factors by a general linear model, separately for singleton and multiple live births and no live births at cycle 1. RESULTS: The study included 93,546 women with two consecutive IVF cycles where the first cycle resulted in a clinical intrauterine pregnancy or a live birth. Among women with a live birth in cycle 1, there was a general pattern of longer IPI for younger women compared to older women. Women with a multiple birth waited longer before initiating a second cycle than women with a singleton birth. For women with no live birth in the first cycle, nearly three fourths initiated cycle 2 within 6 months, regardless of their age. Short (0-5 months) IPI was associated with preterm delivery, older maternal age, and use of donor oocytes. CONCLUSIONS: Age of the mother, outcome of the first pregnancy, and treatment factors affect the length of the interpregnancy interval. Because short IPI has been associated with poor outcomes, women who are at risk for short IPI should be counseled about these outcome risks.

Rationalising polymer selection for supersaturated film forming systems produced by an aerosol spray for the transdermal delivery of methylphenidate.

Film forming systems offer a number of advantages for topical and transdermal drug delivery, in particular enabling production of a supersaturated state which can greatly improve drug absorption and bioavailability. However the suitability of individual film forming polymers to stabilise the supersaturated state and optimise delivery of drugs is not well understood. This study reports the use of differential scanning calorimetry (DSC) to measure the solubility of methylphenidate both as the free base and as the hydrochloride salt in two polymethacrylate copolymers, Eudragit RS (EuRS) and Eudragit E (EuE) and relates this to the ability of films formed using these polymers to deliver methylphenidate across a model membrane. EuRS provided greater methylphenidate delivery when the drug was formulated as the free base in comparison EuE because the lower solubility of the drug in EuRS provided a higher degree of drug saturation in the polymeric film. In contrast EuE provided greater delivery of methylphenidate hydrochloride as EuRS could not prevent its crystallisation from a supersaturated state. Methylphenidate flux across the membrane could be directly related to degree of saturation of the drug in the film formulation as estimated by the drug solubility in the individual polymers demonstrating the importance of drug solubility in the polymer included in film forming systems for topical/transdermal drug delivery. In addition DSC has been demonstrated to be a useful tool for determining the solubility of drugs in polymers used in film forming systems and the approaches outlined here are likely to be useful for predicting the suitability of polymers for particular drugs in film forming transdermal drug delivery systems.

Design, synthesis and characterization of linear unnatural amino acids for skin moisturization.

OBJECTIVES: This work aimed to design, synthesize and characterize replacement natural moisturizing factor (NMF) composed of modified hygroscopic linear amino acids to pre-empt or repair skin barrier dysfunction. METHODS: Following synthesis and characterization, thermo-gravimetric analysis and quantum mechanics molecular modelling quantified and depicted water binding to the new compounds. Deliquescence relative humidity demonstrated the water-scavenging ability of the compounds, whereas snake skin moisturizing studies showed they increased water uptake into snake skin. RESULTS: From thermal analysis, N-hydroxyglycine showed greatest water-holding capacity followed by N-hydroxyserine, l-homoserine and α-hydroxyglycine; coupled with quantum mechanics molecular modelling, between 8 and 12 molecules of water could associate with each molecule of either N-hydroxyglycine, N-hydroxyserine or l-homoserine. All of our modified amino acids were efficacious and induced similar or greater water uptake compared with the established moisturizing compounds hyaluronic acid, glycerine and urea in snake skin. Incorporated at 10% in Oilatum, N-hydroxyserine induced >200% greater moisture uptake into dry snake skin compared to treatment with water alone, with efficacy related to the molecule structure and ability to bind to 12 water molecules. Oilatum cream spiked with all our unnatural amino acid hydrotropes increased water uptake into snake skin compared with Oilatum alone. The compound series was designed to elucidate some structure - efficacy relationships. Amino acid chirality did not affect the water-holding capacity but did affect uptake into skin. Compounds with high melting points and bond energies tended to decrease water-holding capacity. With isosteric replacement, the more electronegative atoms gave greater water-holding capacities. CONCLUSIONS: This work demonstrates the potential of unnatural amino acid hydrotropes as skin moisturizers and has developed some predictive 'rules' for further design and refinement of chemical structures.

An investigation of how fungal infection influences drug penetration through onychomycosis patient's nail plates.

The treatment of onychomycosis remains problematic even though there are several potent antifungal agents available for patient use. The aim of this investigation was to understand whether the structural modifications that arise when a patient's nail become infected plates influences the permeation of drugs into the nail following topical application. It was hoped that through improving understanding of the nail barrier in the diseased state, the development of more effective topical treatments for onychomycosis could be facilitated. The permeation of three compounds with differing hydrophobicities, caffeine, terbinafine and amorolfine (clogD at pH 7.4 of -0.55, 3.72 and 4.49 respectively), was assessed across both healthy and onychomycosis infected, full thickness, human nail plate sections. Transonychial water loss (TOWL) measurements performed on the healthy and diseased nails supported previous observations that the nail behaves like a porous barrier given the lack of correlation between TOWL values with the thicker, diseased nails. The flux of the more hydrophilic caffeine was twofold greater across diseased in comparison with the healthy nails, whilst the hydrophobic molecules terbinafine and amorolfine showed no statistically significant change in their nail penetration rates. Caffeine flux across the nail was found to correlate with the TOWL measurements, though no correlation existed for the more hydrophobic drugs. These data supported the notion that the nail pores, opened up by the infection, facilitated the passage of hydrophilic molecules, whilst the keratin binding of hydrophobic molecules meant that their transport through the nail plate was unchanged. Therefore, in order to exploit the structural changes induced by nail fungal infection it would be beneficial to develop a small molecular weight, hydrophilic antifungal agent, which exhibits low levels of keratin binding.

Localized Epidermal Drug Delivery Induced by Supramolecular Solvent Structuring.

The preferential localization of drug molecules in the epidermis of human skin is considered advantageous for a number of agents, but achieving such a delivery profile can be problematic. The aim of the present study was to assess if the manipulation of solvent supramolecular structuring in the skin could be used to promote drug residence in the epidermal tissue. Skin deposition studies showed that a 175-fold increase in the epidermal loading of a model drug diclofenac (138.65 ± 11.67 µg·cm(-2)), compared to a control (0.81 ± 0.13 µg·cm(-2)), could be achieved by colocalizing the drug with a high concentration of propylene glycol (PG) in the tissue. For such a system at 1 h postdose application, the PG flux into the skin was 9.3 mg·cm(2)·h(-1) and the PG-water ratio in the epidermis was 76:24 (v/v). At this solvent ratio infrared spectroscopy indicated that PG rich supramolecular structures, which displayed a relatively strong physical affinity for the drug, were formed. Encouraging the production of the PG-rich supermolecular structures in the epidermis by applying diclofenac to the skin using a high PG loading dose (240 µg·cm(-2)) produced an epidermal-transdermal drug distribution of 6.8:1. However, generating water-rich solvent supermolecular structures in the epidermis by applying diclofenac using a low PG loading dose (2.2 µg·cm(-2)) led to a loss of preferential epidermal localization of diclofenac in the tissue (0.7:1 epidermal-transdermal drug distribution). This change in diclofenac skin deposition profile in response to PG variations and the accompanying FTIR data supported the notion that supramolecular solvent structures could control drug accumulation in the human epidermis.

Human nail plate modifications induced by onychomycosis: implications for topical therapy.

PURPOSE: Through the characterisation of the human onchomycotic nail plate this study aimed to inform the design of new topical ungual formulations. METHODS: The mechanical properties of the human nail were characterised using a Lloyd tensile strength tester. The nail's density was determined via pycnometry and the nail's ultrastructure by electron microscopy. Raman spectroscopy analysed the keratin disulphide bonds within the nail and its permeability properties were assessed by quantifying water and rhodamine uptake. RESULTS: Chronic in vivo nail plate infection increased human nailplate thickness (healthy 0.49 ± 0.15 mm; diseased 1.20 ± 0.67 mm), but reduced its tensile strength (healthy 63.7 ± 13.4 MPa; diseased 41.7 ± 5.0 MPa) and density (healthy 1.34 ± 0.01 g/cm(3); diseased 1.29 ± 0.00 g/cm(3)). Onchomycosis caused cell-cell separation, without disrupting the nail disulfide bonds or desmosomes. The diseased and healthy nails showed equivalent water uptake profiles, but the rhodamine penetration was 4-fold higher in the diseased nails using a PBS vehicle and 3 -fold higher in an ethanol/PBS vehicle. CONCLUSIONS: Onchomycotic nails presented a thicker but more porous barrier, and its eroded intracellular matrix rendered the tissue more permeable to topically applied chemicals when an aqueous vehicle was used.

Meaningful patient representation informing Canada's cancer drug funding decisions: views of patient representatives on the Pan-Canadian Oncology Drug Review.

In this interview with the patient representatives on the Expert Review Committee (perc) of the Pan-Canadian Oncology Drug Review (pcodr), those representatives offer their views about how to be a valuable contributing member of Canada's national cancer drug funding recommendation committee. The article seeks to inform readers, and especially clinicians, about pcodr from the perspective of the patient representatives.

Effects of triple antioxidant therapy on measures of cardiovascular autonomic neuropathy and on myocardial blood flow in type 1 diabetes: a randomised controlled trial.

AIMS/HYPOTHESIS: We evaluated the effects of a combination triple antioxidant therapy on measures of cardiovascular autonomic neuropathy (CAN) and myocardial blood flow (MBF) in patients with type 1 diabetes. METHODS: This was a randomised, parallel, placebo-controlled trial. Participants were allocated to interventions by sequentially numbered, opaque, sealed envelopes provided to the research pharmacist. All participants and examiners were masked to treatment allocation. Participants were evaluated by cardiovascular autonomic reflex testing, positron emission tomography with [(11)C]meta-hydroxyephedrine ([(11)C]HED) and [(13)N]ammonia, and adenosine stress testing. Markers of oxidative stress included 24 h urinary F2-isoprostanes. Diabetic peripheral neuropathy (DPN) was evaluated by symptoms, signs, electrophysiology and intra-epidermal nerve fibre density. Randomised participants included 44 eligible adults with type 1 diabetes and mild-to-moderate CAN, who were aged 46 ± 11 years and had HbA1c 58 ± 5 mmol/mol (7.5 ± 1.0%), with no evidence of ischaemic heart disease. Participants underwent a 24-month intervention, consisting of antioxidant treatment with allopurinol, α-lipoic acid and nicotinamide, or placebo. The main outcome was change in the global [(11)C]HED retention index (RI) at 24 months in participants on the active drug compared with those on placebo. RESULTS: We analysed data from 44 participants (22 per group). After adjusting for age, sex and in-trial HbA1c, the antioxidant regimen was associated with a slight, but significant worsening of the global [(11)C]HED left ventricle RI (-0.010 [95% CI -0.020, -0.001] p = 0.045) compared with placebo. There were no significant differences at follow-up between antioxidant treatment and placebo in the global MBF, coronary flow reserve, or in measures of DPN and markers of oxidative stress. The majority of adverse events were of mild-to-moderate severity and did not differ between groups CONCLUSIONS/INTERPRETATION: In this cohort of type 1 diabetes patients with mild-to-moderate CAN, a combination antioxidant treatment regimen did not prevent progression of CAN, had no beneficial effects on myocardial perfusion or DPN, and may have been detrimental. However, a larger study is necessary to assess the underlying causes of these findings.

Fluctuating viability selection on morphology of cliff swallows is driven by climate.

The extent to which fluctuating selection can maintain evolutionary stasis in most populations remains an unresolved question in evolutionary biology. Climate has been hypothesized to drive reversals in the direction of selection among different time periods and may also be responsible for intense episodic selection caused by rare weather events. We measured viability selection associated with morphological traits in cliff swallows (Petrochelidon pyrrhonota) in western Nebraska, USA, over a 14-year period following a rare climatic event. We used mark-recapture to estimate the annual apparent survival of over 26 000 individuals whose wing, tail, tarsus and bill had been measured. The fitness functions associated with tarsus length and bill dimensions fluctuated depending on annual climate conditions on the birds' breeding grounds. The oscillating yearly patterns may have slowed and occasionally reversed directional change in trait trajectories, although there was a trend over time for all traits except tarsus to increase in size. The net positive directional selection on some traits, despite periodic climate-associated fluctuations, suggests that cliff swallow morphology in the population is likely to keep changing and supports recent work contending that selection in general does not fluctuate enough to be an effective driver of stasis.

The influence of self-assembling supramolecular structures on the passive membrane transport of ion-paired molecules.

Weak ion-ion interactions, such as those associated with ion-pair formation, are difficult to isolate and characterise in the liquid state, but they have the potential to alter significantly the physicochemical behaviour of molecules in solution. The aim of this work was to gain a better understanding of how ion-ion interactions influenced passive membrane transport. The test system was composed of propylene (PG) glycol, water and diclofenac diethylamine (DDEA). Infrared spectroscopy was employed to determine the nature of the DDEA ion-pair interactions and the drug-vehicle association. Passive transport was assessed using homogeneous synthetic membranes. Solution-state analysis demonstrated that the ion-pair was unperturbed by vehicle composition changes, but the solvent-DDEA interactions were modified. DDEA-PG/water hydrogen bonding influenced the ion-pair solubility (X(dev)) and the solvent interactions slowed transport rate in PG-rich vehicles (0.84±0.05 µg cm(-2) h(-1), at ln(X(dev))=0.57). In water-rich co-solvents, the presence of strong water structuring facilitated a significant increase (p<0.05) in transmembrane penetration rate (e.g. 4.33±0.92 µg cm(-2) h(-1), at ln(X(dev))=-0.13). The data demonstrates that weak ion-ion interactions can result in the embedding of polar entities within a stable solvent complex and spontaneous supramolecular assembly should be considered when interpreting transmembrane transport processes of ionic molecules.

Triggered in situ drug supersaturation and hydrophilic matrix self-assembly.

PURPOSE: To understand in situ drug thermodynamic activity when embedded in a supramolecular structured hydrophilic matrix that simultaneously self-assembled during drug supersaturation. METHODS: A propylene glycol (PG)/water, hydroxypropyl methyl cellulose matrix containing ethanol was used to support diclofenac supersaturation. Phase behaviour, thermodynamics and drug transport were assessed through the determination of evaporation kinetics, supersaturation kinetics and transmembrane penetration. RESULTS: Initial ethanol evaporation from the drug loaded matrix (2.9 ± 0.4 mg.min(-1).cm(-2)) was comparable to that of the pure solvent (ca. 3 mg.min(-1).cm(-2)). When 25% w/w of the total ethanol from the applied phase was lost (ethanol/water/PG molar ratio of 7:5:1.2), an inflection point in the evaporation profile and a sudden decrease in drug solubility demonstrated that a defined supramolecular structure was formed. The 55-fold decrease in drug solubility observed over the subsequent 8 h drove in situ supersaturation, the rate of which was a function of the drug load in the matrix (y = 0.0078x, R(2) < 0.99). CONCLUSION: The self-assembling supramolecular matrix prevented drug re-crystallisation for >24 h, but did not hinder mobility and this allowed the thermodynamic activity of the drug to be directly translated into highly efficient transmembrane penetration.

Discriminating the molecular identity and function of discrete supramolecular structures in topical pharmaceutical formulations.

There is a need to understand how solvent structuring influences drug presentation in pharmaceutical preparations, and the aim of this study was to characterize the properties of propylene glycol (PG)/water supramolecular structures such that their functional consequences on drug delivery could be assessed. Shifts to higher wavenumbers in the C-H and C-O infrared stretching vibrations of PG (up to 8.6 and 11 cm(-1), respectively) implied that water supramolecular structures were being formed as a consequence of hydrophobic hydration. However, unlike analogous binary solvent systems, water structuring was not enhanced by the presence of the cosolvent. Two discrete populations of supramolecular structures were evident from the infrared spectroscopy: water-rich structures, predominant below a PG volume fraction (f(PG)) of 0.4 (unmoving water bending vibration at 1211 cm(-1)) and PG-rich structures, predominant above 0.4 f(PG) (both C-H and water peaks moved to lower wavenumbers). The un-ionized diclofenac log-linear solubility and transmembrane transport altered dramatically when f(PG) > 0.55 (a 10-fold increase in transport from 0.28 ± 0.06 µg·cm(-2)·h(-1) at 0.2 f(PG) to 2.81 ± 0.16 µg·cm(-2)·h(-1) at 0.9 f(PG)), and this demonstrated the ability of the PG rich supramolecular structures, formed in the PG/water solvent, to specifically modify the behavior of un-ionized diclofenac.