Medium-Chain Triacylglycerols (MCTs) and Their Fractions in Drug Delivery Systems : A Systematic Review.

Medium-chain triacylglycerol (MCT) is a type of triacylglycerol that has six or seven to twelve carbon chains. It consists of three molecules of fatty acids attached to one molecule of glycerol. Drug delivery system (DDS) is defined as a formulation to distribute drugs into the human body. The unique properties of MCTs have garnered interest in using them as excipients in DDS. Even though there are many significant effects attributed to the use of MCTs, especially in modulating the rate of drug delivery in various DDS, they are all limited and intermittent. This warrants a detailed summary of the previous studies on the use of MCTs in various DDS. Therefore, this review focuses on presenting a systematic review of previous studies on the use of MCTs in the last six years and explores the types and effects of MCTs on DDS that employ various types of delivery routes. A systematic search through PubMed, Science Direct and Scopus was performed. Keywords like "medium-chain triglycerides", "medium-chain fatty acids", "medium-chain triglycerides and their fractions", "medium-chain fatty acids and their fractions", "MCTs", "MCFA", "in drug delivery", "in drug delivery system" and their combinations were used. The synonyms of the words were also used to extend the search. A total of 17 articles that met the inclusion criteria were identified. Findings from this review have identified the several MCTs and their fractions used in DDS that employed the oral/enteral, topical, transdermal, parenteral, and pulmonary routes of drug delivery. The review also highlights that the usage of MCTs in DDS results in a better transportation of drugs into the human body.

Nanostructured Lipid Carriers for the Delivery of Natural Bioactive Compounds.

Natural products contain bioactive compounds that are produced naturally via synthetic or semisynthetic processes. These bioactive compounds play significant biological roles, especially for growth as well as in defense mechanisms against pathogens. Bioactive compounds in natural products have been extensively studied in recent decades for their pharmacological activities, such as anticancer, wound healing, anti-microbial, anti-inflammatory, and anti-oxidative properties. However, their pharmaceutical significance has always been hindered by their low bioavailability and instability with variations in pH, temperature, and exposure to light. Nanotechnology paves the way for the development of drug delivery systems by enhancing therapeutic efficacy. Nanostructured lipid carriers, a lipidbased drug delivery system, are recently being studied to improve the biocompatibility, biodegradability, bioavailability, solubility, permeability, and shelf life of bioactive compounds in the pharmaceutical industry. The ideal component and preparation method for bioactive compounds in nanostructured lipid carrier development is necessary for their physicochemical properties and therapeutic efficiency. Therefore, this review seeks to highlight recent developments, preparation, and application of nanostructured lipid carriers as carriers for natural bioactive compounds in improving their therapeutic potential in drug delivery systems.

Cetyltrimethylammonium bromide-nanocrystalline cellulose (CTAB-NCC) based microemulsions for enhancement of topical delivery of curcumin.

Low bioavailability and poor water solubility have limited the utilization of curcumin in conventional dosing methods. As an alternative, microemulsions as drug carrier can improve curcumin delivery. A cetyltrimethylammonium bromide-nanocrystalline cellulose (CTAB-NCC)-based microemulsion was developed and its potential use as a topical delivery method for curcumin was investigated. The effect of microemulsion's particle size and its microstructure as well as the presence of the CTAB-NCC nanoparticle on the topical delivery of curcumin was studied. In vitro permeation studies showed higher penetration rate of curcumin from the oil-in-water type-microemulsions. The skin permeation profile of curcumin followed Higuchi release kinetics. Furthermore, use of the (CTAB-NCC)-based microemulsion enhanced curcumin accumulation in the skin and these system showed non cytotoxicity effect on L929 cell line. These results showed the potential of (CTAB-NCC)-based microemulsions as controlled-release topical systems for the delivery of curcumin and potentially other lipophilic drugs.

Development, characterization and pharmacokinetics of mupirocin-loaded nanostructured lipid carriers (NLCs) for intravascular administration.

Mupirocin is a promising broad-spectrum antibiotic that is effective in treating MRSA infections. However, due to its rapid elimination and hydrolysis following injection and high protein binding, current therapeutic use is limited to topical administration. Nanotechnology-driven innovations provide hope for patients and practitioners in overcoming the problem of drug degradation by encapsulation. The objective of this research is to develop and characterize Mupirocin-Loaded Nanostructured Lipid Carriers (M-NLC) for intravascular administration. The MNLC was produced by a combination of high shear homogenization and high pressure homogenization of solid (cetyl palmitate) and liquid (caprylic/caprylic acid) biocompatible lipids in 5 different ratios. The mean particle size, polydispersity index (PDI) and the zeta potential (ZP) of the MNLC formulations were between 99.8 and 235 nm, PDI lower than 0.164, ZP from -25.96 to -19.53 and pH ranging from 6.28-6.49. The MNLC formulation also enhances the anti-bacterial activity of mupirocin. All formulation showed sustained drug release and good physical characteristics for three months storage under 25 °C. It also revealed that the MNLC 1 is safe at 250 mg/kg dose in rats. The MNLC 1 also showed a significant increase in plasma concentration in rabbits following IV administration thus, demonstrating an enhancement on its pharmacokinetic profile as compared to free mupirocin.

Influence of omega fatty acids on skin permeation of a coenzyme Q10 nanoemulsion cream formulation: characterization, in silico and ex vivo determination.

Objective: The aim of this study was to develop a coenzyme Q10 nanoemulsion cream, characterize and to determine the influence of omega fatty acids on the delivery of coenzyme Q10 across model skin membrane via ex vivo and in silico techniques. Methods: Coenzyme Q10 nanoemulsion creams were prepared using natural edible oils such as linseed, evening primrose, and olive oil. Their mechanical features and ability to deliver CoQ10 across rat skin were characterized. Computational docking analysis was performed for in silico evaluation of CoQ10 and omega fatty acid interactions. Results: Linseed, evening primrose, and olive oils each produced nano-sized emulsion creams (343.93-409.86 nm) and exhibited excellent rheological features. The computerized docking studies showed favorable interactions between CoQ10 and omega fatty acids that could improve skin permeation. The three edible-oil nanoemulsion creams displayed higher ex vivo skin permeation and drug flux compared to the liquid-paraffin control cream. The linseed oil formulation displayed the highest skin permeation (3.97 ± 0.91 mg/cm2) and drug flux (0.19 ± 0.05 mg/cm2/h). Conclusion: CoQ10 loaded-linseed oil nanoemulsion cream displayed the highest skin permeation. The highest permeation showed by linseed oil nanoemulsion cream may be due to the presence of omega-3, -6, and -9 fatty acids which might serve as permeation enhancers. This indicated that the edible oil nanoemulsion creams have potential as drug vehicles that enhance CoQ10 delivery across skin.

A new alternative for intravenous lipid emulsion 20% w/w from superolein oil and its effect on lipid and liver profiles in an animal model.

PURPOSE: Intravenous lipid emulsion (IVLE) was first used to prevent essential fatty acids deficiency. IVLE with α-tocopherol was reported to provide protection against parenteral nutrition-associated liver disease. This study aims to determine the optimal parameters and conditions in developing a physically stable IVLE from superolein palm oil (SoLE 20%) and its effect on lipid and liver profiles in an animal model. METHODS: SoLE 20% was prepared using superolein oil and MCT oil (1:1), stabilized with egg lecithin and homogenized using a high pressure homogenizer. Mean droplet size was used as the response variable and was measured using laser diffraction and dynamic light scattering method. Physical stability at 4 °C, 25 °C and 40 °C storage temperatures were determined based on particle size and distribution, polydispersity index, zeta potential, viscosity, vitamin E contents and pH. Sterility and pyrogenicity were also investigated. Rabbits were administered with 1.0 g/kg SoLE 20% for 5 h and repeated daily for 3 days to investigate its effect on blood lipid and liver enzymes profile. RESULTS: SoLE 20% was succesfully prepared using the optimized parameters of 800 psi, 7 cycles and 1.2 g lecithin. The IVLE prepared had a particle size of 252.60 ± 4.88 nm and was physically stable for 4 weeks at different storage temperatures. SoLE 20% had a high content of natural vitamin E, remained sterile and pyrogen free. It was also safe for intravenous administration and did not alter the blood lipid (p > 0.05) and liver enzymes profiles (p > 0.05) of the rabbits. CONCLUSION: The optimal parameters to develop a stable superolein based IVLE are 800 psi homogenization pressure, 7 homogenization cycles and using 1.2 g lecithin as the emulsifier. SoLE 20% is safe for intravenous administration and does not significantly alter lipid and liver enzymes profiles of the rabbits.

Potential treatment of atopic dermatitis: tolerability and safety of cream containing nanoparticles loaded with hydrocortisone and hydroxytyrosol in human subjects.

Hydrocortisone (HC), topical glucocorticoid along with hydroxytyrosol (HT), and anti-microbial- and anti-oxidant-loaded chitosan nanoparticles (CSNPs) were prepared in large scale and analyzed for their adverse effects on healthy human skin followed by repeated applications. Ten subjects were randomized to receive test (HC-HT CSNPs) and vehicle samples (aqueous (AQ) cream). They were applied on the arms for 28 days, and transepidermal water loss (TEWL), erythema intensity, and irritation score were measured. Blood samples were analyzed for blood hematology, blood biochemistry, and adrenal cortico-thyroid hormone (ACTH) levels. Skin biopsy was obtained to assess histopathological changes in the skin. HC-HT CSNP AQ cream was stored at 4, 25, and 45 °C for a period of 1 year, and its stability was assessed by monitoring their physical appearances, particle size, and pH. Spherical-shaped NPs were successfully upscaled using spinning-disc technology, with insignificant changes in particle size, zeta potential, and incorporation of drugs as compared to the well-established laboratory method. Particle size of HC-HT CSNPs was < 250 nm, and HC-HT CSNPs AQ cream remained stable when stored at 25 °C. TEWL and erythema intensity for 28-day application did not indicate any signs of local irritation, redness, and toxicity, which were confirmed by normal Draize skin irritation scoring system and skin hematoxylin and eosin (H&E) staining results. Comparative results of blood hematology, blood biochemistry, and adrenal cortico-thyroid hormone level at day 0 and day 28 were not significant, indicating non-systemic toxicity. In conclusion, HC-HT CSNP AQ cream is safe, well-tolerated, and non-toxic, which may be useful in treating atopic dermatitis.

Topical application of omega-3-, omega-6-, and omega-9-rich oil emulsions for cutaneous wound healing in rats.

Wound healing is a physiological event that generates reconstitution and restoration of granulation tissue that ends with scar formation. As omega fatty acids are part of membrane phospholipids and participate in the inflammatory response, we investigated the effects of omega-3, omega-6, and omega-9 fatty acids in the form of oils on wound healing. Linseed (LO), evening primrose (EPO), and olive oils (OO) rich in omega-3, omega-6, and omega-9 fatty acids were formulated into emulsions and were topically applied on rats with excision wounds. All omega-3-, omega-6-, and omega-9-rich oil formulations were found to accelerate wound closure compared to untreated, with significant improvement (p < 0.05) being observed at day 14. EPO induced early deposition of collagen as evaluated by Masson trichrome staining that correlated well with the hydroxyproline content assay, with the highest level at days 3 and 7. Vascular endothelial growth factor (VEGF) showed greater amount of new microvasculature formed in the EPO-treated group, while moderate improvement occurs in the LO and OO groups. EPO increased both the expression of proinflammatory cytokines and growth factors in the early stage of healing and declined at the later stage of healing. LO modulates the proinflammatory cytokines and chemokine but did not affect the growth factors. In contrast, OO induced the expression of growth factors rather than proinflammatory cytokines. These data suggest that LO, EPO, and OO emulsions promote wound healing but they accomplish this by different mechanisms.

Coenzyme Q10-Loaded Fish Oil-Based Bigel System: Probing the Delivery Across Porcine Skin and Possible Interaction with Fish Oil Fatty Acids.

Coenzyme Q10 (CoQ10) is a vitamin-like oil-soluble molecule that has anti-oxidant and anti-ageing effects. To determine the most optimal CoQ10 delivery vehicle, CoQ10 was solubilised in both water and fish oil, and formulated into hydrogel, oleogel and bigel. Permeability of CoQ10 from each formulation across porcine ear skin was then evaluated. Furthermore, the effects of the omega-3 fatty eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids from fish oil on skin permeation were investigated by means of nuclear magnetic resonance (NMR) and computerised molecular modelling docking experiments. The highest drug permeation was achieved with the bigel formulation that proved to be the most effective vehicle in delivering CoQ10 across the skin membrane due to a combination of its adhesive, viscous and lipophilic properties. Furthermore, the interactions between CoQ10 and fatty acids revealed by NMR and molecular modelling experiments likely accounted for skin permeability of CoQ10. NMR data showed dose-dependent changes in proton chemical shifts in EPA and DHA. Molecular modelling revealed complex formation and large binding energies between fatty acids and CoQ10. This study advances the knowledge about bigels as drug delivery vehicles and highlights the use of NMR and molecular docking studies for the prediction of the influence of drug-excipient relationships at the molecular level.

Novel Fish Oil-based Bigel System for Controlled Drug Delivery and its Influence on Immunomodulatory Activity of Imiquimod Against Skin Cancer.

PURPOSE: To characterize bigel system as a topical drug delivery vehicle and to establish the immunomodulatory role of imiquimod-fish oil combination against skin cancer and inflammation resulting from chemical carcinogenesis. METHODS: Imiquimod-loaded fish oil bigel colloidal system was prepared using a blend of carbopol hydrogel and fish oil oleogel. Bigels were first characterized for their mechanical properties and compared to conventional gel systems. Ex vivo permeation studies were performed on murine skin to analyze the ability of the bigels to transport drug across skin and to predict the release mechanism via mathematical modelling. Furthermore, to analyze pharmacological effectiveness in skin cancer and controlling imiquimod-induced inflammatory side effects, imiquimod-fish oil combination was tested in vitro on epidermoid carcinoma cells and in vivo in Swiss albino mice cancer model. RESULTS: Imiquimod-loaded fish oil bigels exhibited higher drug availability inside the skin as compared to individual imiquimod hydrogel and oleogel controls through quasi-Fickian diffusion mechanism. Imiquimod-fish oil combination in bigel enhanced the antitumor effects and significantly reduced serum pro-inflammatory cytokine levels such as tumor necrosis factor-alpha and interleukin-6, and reducing tumor progression via inhibition of vascular endothelial growth factor. Imiquimod-fish oil combination also resulted in increased expression of interleukin-10, an anti-inflammatory cytokine, which could also aid anti-tumor activity against skin cancer. CONCLUSION: Imiquimod administration through a bigel vehicle along with fish oil could be beneficial for controlling imiquimod-induced inflammatory side effects and in the treatment of skin cancer.

In vivo response of GsdmA3(Dfl)/+ mice to topically applied fish oil - effects on cellular markers and macrophages.

Psoriasis is an incurable autoimmune disease characterized by patches of abnormal red, itchy and scaly skin. This work examined the modulation of inflammation, hyperproliferation and immune cell markers following topical application of fish oil (FO) in comparison to the antipsoriatic agents, betamethasone dipropionate (BD) and salicylic acid (SA), to GsdmA3(Dfl)/+ mice, a hair loss mutant which also exhibits epidermal hyperproliferation akin to psoriasis. The mice were dosed with 100 mg of the test formulation and after 10 days, the mice were sacrificed, skin sections excised and subjected to immunohistochemical determination of COX-2, K17 and MAC-1; and immunofluorescence of Ki-67. Unchanged expression of the proinflammatory enzyme COX-2 was observed in all treatments, suggesting the noninvolvement of COX-2 in the aetiology of cutaneous aberration seen in GsdmA3(Dfl)/+ mice. Intense staining of K17 and MAC-1 in the FO-treated group mirrored the epidermal thickening seen observed in live mice by optical coherence tomography (OCT). The ratio of Ki-67-positive nuclei per 100 basal cells indicated that hyperproliferation of keratinocytes occurred in FO-treated mice and the opposite was true for BD-treated mice. There was a positive correlation (R (2) 0.995) between Ki-67 and the epidermal thickness data observed previously. In all immunochemical procedures, the combined BD, SA and FO formulation did not show any significant difference with the control group, reflecting observations seen previously. In conclusion, the epidermal changes observed following topical FO treatment on GsdmA3(Dfl)/+ mice involves an increase in cellular proliferation and macrophages, although COX-2 does not appear to play an important role.

In-vivo dermal pharmacokinetics, efficacy, and safety of skin targeting nanoparticles for corticosteroid treatment of atopic dermatitis.

The objective of this study was to investigate the in-vivo behavior of topically applied cationic polymeric chitosan nanoparticles (CSNPs) loaded with anti-inflammatory (hydrocortisone, HC) and antimicrobial (hydroxytyrosol, HT) drugs, to elucidate their skin targeting potential for the treatment of atopic dermatitis (AD). Compared to the commercial formulation, the HC-HT loaded CSNPs showed significantly improved drug penetration into the epidermal and dermal layers of albino Wistar rat skin without saturation. Dermal pharmacokinetic of CSNPs with a size of 228.5±7nm and +39±5mV charges revealed that they penetrated 2.46-fold deeper than the commercial formulation did, and had greater affinity at the skin target site without spreading to the surrounding tissues, thereby providing substantial safety benefits. In repeated dermal application toxicity studies, the HC-HT CSNPs showed no evidence of toxicity compared to the commercial formulation, which induced skin atrophy and higher liver enzyme levels. In conclusion, the positively charged HC-HT CSNP formulation exhibited promising local delivery and virtually no treatment-related toxicities, suggesting it may be an efficient and viable alternative for commercially available AD treatments.

Immunomodulatory Effectiveness of Fish Oil and omega-3 Fatty Acids in Human Non-melanoma Skin Carcinoma Cells.

Fish oil is composed of various fatty acids among which omega-3 fatty acids are considered as most beneficial. The effects of fish oil on the activity of a topical anticancer drug, imiquimod, and the immunomodulatory activity of omega-3 fatty acids was investigated in human basal and squamous cell carcinoma cell lines. Imiquimod-fish oil mixture exhibited higher carcinoma cell growth inhibition and immunomodulatory activity than imiquimod alone, especially against squamous cell carcinoma cells. Omega-3 fatty acids exhibited growth inhibition of both basal cell and squamous cell carcinoma cell lines and modulated the immune response. Omega-3 fatty acids of fish oil serve as inducers of interleukin-10, an anti-inflammatory cytokine, and as suppressors of interleukin-6 and tumor necrosis factor-alpha, which not only depress tumor growth but also adequately control the inflammatory side effects of imiquimod. Thus, imiquimod administration with fish oil could be beneficial for inhibition of non-melanoma skin carcinoma cells but further in vivo studies are needed to understand their role in skin cancer.

Minimization of Local and Systemic Adverse Effects of Topical Glucocorticoids by Nanoencapsulation: In Vivo Safety of Hydrocortisone-Hydroxytyrosol Loaded Chitosan Nanoparticles.

Hydrocortisone (HC) is a topical glucocorticoid for the treatment of atopic dermatitis (AD); the local as well as systemic side effects limit its use. Hydroxytyrosol (HT) is a polyphenol present in olive oil that has strong antimicrobial and antioxidant activities. HC-HT coloaded chitosan nanoparticles (HC-HT CSNPs) were therefore developed to improve the efficacy against AD. In this study, HC-HT CSNPs of 235 ± 9 nm in size and with zeta potential +39.2 ± 1.6 mV were incorporated into aqueous cream (vehicle) and investigated for acute dermal toxicity, dermal irritation, and repeated dose toxicity using albino Wistar rats. HC-HT CSNPs exhibited LD50 > 125 mg/body surface area of active, which is 100-fold higher than the normal human dose of HC. Compared with the commercial formulation, 0.5 g of HC-HT CSNPs did not cause skin irritation, as measured by Tewameter®, Mexameter®, and as observed visually. Moreover, no-observed-adverse-effect level was observed with respect to body weight, organ weight, feed consumption, blood hematological and biochemical, urinalysis, and histopathological parameters at a dose of 1000 mg/body surface area per day of HC-HT CSNPs for 28 days. This in vivo study demonstrated that nanoencapsulation significantly reduced the toxic effects of HC and this should allow further clinical investigations.

Probing the effects of fish oil on the delivery and inflammation-inducing potential of imiquimod.

Imiquimod is a chemotherapeutic agent for many skin-associated diseases, but it has also been associated with inflammatory side effects. The aim of this study was to prevent the inflammatory effect of commercial imiquimod (Aldara(®)) by controlled release of imiquimod through a hydrogel/oleogel colloidal mixture (CA bigel) containing fish oil as an anti-inflammatory agent. Imiquimod permeability from Aldara® cream and bigel through mice skin was evaluated, and the drug content residing in the skin via the tape stripping technique was quantified. The fish oil fatty acid content in skin along with its lipophilic environment was also determined. An inflammation study was conducted using animal models, and Aldara(®) cream was found to potentially cause psoriasis-like inflammation, which could be owing to prolonged application and excessive drug permeation. Controlled release of imiquimod along with fish oil through CA bigel may have caused reduced imiquimod inflammation. NMR studies and computerized molecular modeling were also conducted to observe whether the fish oil and imiquimod formed a complex that was responsible for improving imiquimod transport and reducing its side effects. NMR spectra showed dose-dependent chemical shifts and molecular modeling revealed π-σ interaction between EPA and imiquimod, which could help reduce imiquimod inflammation.

Development and physical characterization of polymer-fish oil bigel (hydrogel/oleogel) system as a transdermal drug delivery vehicle.

Polymer-Fish oil bigel (hydrogel/oleogel colloidal mixture) was developed by using fish oil and natural (sodium alginate) and synthetic (hydroxypropyl methylcellulose) polymer for pharmaceutical purposes. The bigels were closely monitored and thermal, rheological and mechanical properties were compared with the conventional hydrogels for their potential use as an effective transdermal drug delivery vehicle. Stability of the fish oil fatty acids (especially eicosapentanoic acid, EPA and docosahexanoic acid, DHA) was determined by gas chromatography and the drug content (imiquimod) was assessed with liquid chromatography. Furthermore, in vitro permeation study was conducted to determine the capability of the fish oil-bigels as transdermal drug delivery vehicle. The bigels showed pseudoplastic rheological features, with excellent mechanical properties (adhesiveness, peak stress and hardness), which indicated their excellent spreadability for application on the skin. Bigels prepared with mixture of sodium alginate and fish oil (SB1 and SB2), and the bigels prepared with the mixture of hydroxypropyl methylcellulose and fish oil (HB1-HB3) showed high cumulative permeation and drug flux compared to hydrogels. Addition of fish oil proved to be beneficial in increasing the drug permeation and the results were statistically significant (p < 0.05, one-way Anova, SPSS 20.0). Thus, it can be concluded that bigel formulations could be used as an effective topical and transdermal drug delivery vehicle for pharmaceutical purposes.

Recent advances in gel technologies for topical and transdermal drug delivery.

Transdermal drug delivery systems are a constant source of interest because of the benefits that they afford in overcoming many drawbacks associated with other modes of drug delivery (i.e. oral, intravenous). Because of the impermeable nature of the skin, designing a suitable drug delivery vehicle that penetrates the skin barrier is challenging. Gels are semisolid formulations, which have an external solvent phase, may be hydrophobic or hydrophilic in nature, and are immobilized within the spaces of a three-dimensional network structure. Gels have a broad range of applications in food, cosmetics, biotechnology, pharmatechnology, etc. Typically, gels can be distinguished according to the nature of the liquid phase, for example, organogels (oleogels) contain an organic solvent, and hydrogels contain water. Recent studies have reported other types of gels for dermal drug application, such as proniosomal gels, emulgels, bigels and aerogels. This review aims to introduce the latest trends in transdermal drug delivery via traditional hydrogels and organogels and to provide insight into the latest gel types (proniosomal gels, emulgels, bigels and aerogels) as well as recent technologies for topical and transdermal drug delivery.

The effects of betamethasone dipropionate and fish oil on HaCaT proliferation and apoptosis.

The current work examined the effect of fish oil (FO) and betamethasone dipropionate (BD) on the growth of immortalized HaCaT keratinocytes. HaCaT cells were grown and treated with FO and/or BD, and proliferation determined using the MTT method. The cells were further probed by immunocytochemistry (ICC) techniques for apoptosis using Cleaved Caspase-3 Asp175, and inflammatory processes using cyclooxygenase-2 (COX-2). The addition of FO increased the inhibition of HaCaT cells by 27.2%, from 43.15% to 70.35% compared to BD alone (p 0.034). FO alone appeared to induce expression of Asp175 and the effect was greater in combination with BD. The net effect, however, were less than BD alone. Similar observations were seen with regards to COX-2 inhibition. The added benefits of FO to the effect of BD on the inhibition of cell growth, induction of apoptosis and inhibition of inflammation have now been demonstrated on a cellular level. Each of these activities supports beneficial effects in hyperproliferative skin disorders, such as psoriasis.

Alginate based bilayer hydrocolloid films as potential slow-release modern wound dressing.

The aims of this research were to develop a novel bilayer hydrocolloid film based on alginate and to investigate its potential as slow-release wound healing vehicle. The bilayer is composed of an upper layer impregnated with model drug (ibuprofen) and a drug-free lower layer, which acted as a rate-controlling membrane. The thickness uniformity, solvent loss, moisture vapour transmission rate (MVTR), hydration rate, morphology, rheology, mechanical properties, in vitro drug release and in vivo wound healing profiles were investigated. A smooth bilayer film with two homogenous distinct layers was produced. The characterisation results showed that bilayer has superior mechanical and rheological properties than the single layer films. The bilayers also showed low MVTR, slower hydration rate and lower drug flux in vitro compared to single layer inferring that bilayer may be useful for treating low suppurating wounds and suitable for slow release application on wound surfaces. The bilayers also provided a significant higher healing rate in vivo, with well-formed epidermis with faster granulation tissue formation when compared to the controls. In conclusions, a novel alginate-based bilayer hydrocolloid film was developed and results suggested that they can be exploited as slow-release wound dressings.

In vivo response of GsdmA3Dfl/+ mice to topically applied anti-psoriatic agents: effects on epidermal thickness, as determined by optical coherence tomography and H&E staining.

This study evaluated in vivo the potential of optical coherence tomography (OCT) to determine changes in thickness of the epidermis in response to the topically applied anti-psoriatics betamethasone dipropionate (BD), salicylic acid (SA) and also fish oil (FO). GsdmA3Dfl/+ mice have an inflammatory hair loss phenotype that includes hyperproliferation and epidermal thickening, hence a potential psoriasis model. Changes in epidermal thickness were evaluated over a period of 10 days, with the mice treated with combined BD + SA, FO + SA and BD + FO + SA. The data were validated with conventional measurement using H&E staining coupled with microscopy. Initial baseline measurement revealed an average epidermal thickness of 26.92 ± 1.17 µm. After 10 days of treatment with BD, the average epidermal thickness was reduced by 38.8% (P = 0.0001), and inversely, treatment with FO resulted in an unexpected 105% increase (P = 0.0001) in epidermal thickness. Combined BD + FO treatment did not cause any significant change (P = 0.3755) and may further indicate opposing effects on keratinocyte proliferation. The data obtained using OCT were statistically the same as those obtained by H&E/microscopy (P = 0.4325), supporting a greater role for OCT in dermatological studies, while also allowing a reduction in the number of animals used in such studies as sacrifice at individual timepoints is not necessary.