Choline-based ionic liquids enhance the dermal delivery of cyclosporine a for potential treatment of psoriasis.

Psoriasis is a prevalent chronic disease affecting 2-3% of the global population. Cyclosporine A (CyA) has been widely used with great promise in the treatment of moderate to severe psoriasis despite various side effects associated with its systemic administration. Topical administration of CyA circumvents systemic side effects; however, the poor water solubility and large molecular weight of CyA pose challenges for dermal delivery. In this study, choline-based ionic liquids (ILs) were used to enhance the dermal delivery of CyA for the potential treatment of psoriasis. All four ILs tested significantly improved the solubility of CyA, which was greater than that of the control group with dimethyl sulfoxide (DMSO) as a solubilizer (20%, w/w). The saturated solubility of CyA in two of the ILs, choline geranate ([Ch][Ge]) and choline ricinoleate ([Ch][Ra]), reached more than 90 mg/mL, and the solubilization capability of the ILs except [Ch][Ci] was resistant to water dilution. The negligible change in CyA content determined by high-performance liquid chromatography and the secondary structure detected by circular dichroism spectroscopy confirmed the stability of CyA in the ILs. At 4 h in the in vitro penetration test, the amount of CyA retained in the skin in the IL groups was slightly greater than that in the control group (20% DMSO). The water content of the ILs significantly affected their penetration ability. When the water content increased from 10 to 70%, the dermal delivery of CyA first increased, peaked at a water content of 30%, and then decreased. The dermal delivery ability of [Ch][Ge] and [Ch][Ra] with a water content of 70% was still comparable to that of 20% DMSO. Moreover, CyA-loaded ILs (0.5%, w/w) significantly relieved the symptoms of psoriasis in an imiquimod (IMQ)-induced mouse model, and the levels of inflammatory factors, including tumor necrosis factor α, interleukin 22 and interleukin 17, in the affected area were reduced by 71.7%, 75.6%, and 89.3%, respectively. The IL tested, choline sorbate ([Ch][So]), showed low cytotoxicity to human immortalized epidermal cells (HaCaT). After 7 days of consecutive application, [Ch][So] did not cause significant irritation. In conclusion, ILs demonstrate promising potential for the dermal delivery of CyA for the treatment of psoriasis.

Impact of solvent dry down, phase change, vehicle pH and slowly reversible keratin binding on skin penetration of cosmetic relevant compounds: II. Solids.

We extended a mechanistic, physics-based framework of the dry down process, previously developed for liquids and electrolytes, to solids and coded it into the latest UB/UC/P&G skin permeation model, herein renamed DigiSkin. The framework accounts for the phase change of the permeant from dissolved in a solvent (liquid) to precipitated on the skin surface (solid). The evaporation rate for the solid is reduced due to lower vapor pressure for the solid state versus subcooled liquid. These vapor pressures may differ by two orders of magnitude. The solid may gradually redissolve and penetrate the skin. The framework was tested by simulating the in vitro human skin permeation of the 38 cosmetically relevant solid compounds reported by Hewitt et al., J. Appl. Toxicol. 2019, 1-13. The more detailed handling of the evaporation process greatly improved DigiSkin evaporation predictions (r2 = 0.89). Further, we developed a model reliability prediction score classification using diverse protein reactivity data and identified that 15 of 38 compounds are out of model scope. Dermal delivery predictions for the remaining chemicals have excellent agreement with experimental data. The analysis highlighted the sensitivity of water solubility and equilibrium vapor pressure values on the DigiSkin predictions outcomes influencing agreement with the experimental observations.

Design and Biocompatibility of Biodegradable Poly(octamethylene suberate) Nanoparticles to Treat Skin Diseases.

Biodegradable aliphatic polyester formulations as carriers for topical drug delivery show the potential to encapsulate structurally different therapeutic compounds. Poly(octamethylene suberate) (POS) nanoparticles (POS-NPs) were used as a matrix to encapsulate four therapeutic molecules used to treat skin disorders: caffeine (CF), quercetin (QR), hydrocortisone (HC), and adapalene (AD). Hydrophobicity and chemical structure of bioactive compounds (BCs) influenced the physicochemical stability of drug-loaded nanoparticles. The particle size of drug-loaded nanoparticles was between 254.9 nm for the CF-POS-NP and 1291.3 for QR-POS-NP. Particles had a negative charge from -27.6 mV (QR) to -49.2 mV (HC). Drug loading content for all BC-POS-NPs varies between 36.11 ± 1.48% (CF-POS-NP) and 66.66 ± 4.87% (AD-POS-NP), and their entrapment efficiency is relatively high (28.30 ± 1.81% and 99.95 ± 0.04%, respectively). Calorimetric analysis showed the appearance of polymorphism for AD- and HC-loaded systems and the drug's complete solubilisation into all nanoparticle formulations. FTIR and NMR spectra showed apparent drug incorporation into the polymer matrix of NPs. The encapsulation of BCs enhanced the antioxidative effect. The prepared POS nanoparticles' cytotoxicity was studied using two dermal cell lines, keratinocyte (HaCaT) cells and fibroblasts (HDFn). The nanoparticle cytotoxic effect was more substantial on HaCaT cell lines. A reconstructed human epidermis (RHE) was successfully used to investigate the penetration of polymeric NPs. Based on permeation and histology studies, HC-POS-NPs and CF-POS-NPs were shown not to be suitable for dermal applications with the explored drug concentrations. AD presents a high permeation rate and no toxic impact on RHE.

Formulation and dermal delivery of a new active pharmaceutical ingredient in an in vitro wound model for the treatment of chronic ulcers.

The aim of this study was to investigate dermal delivery of the new active pharmaceutical ingredient (API) TOP-N53 into diabetic foot ulcer using an in vitro wound model consisting of pig ear dermis and elucidate the impact of drug formulation and wound dressing taking into consideration clinical relevance in the home care setting and possible bacterial infection. Different formulation approaches for the poorly water-soluble API including colloidal solubilization, drug micro-suspension and cosolvent addition were investigated; moreover, the effect of (micro-)viscosity of hydrogels used as primary wound dressing on delivery was assessed. Addition of Transcutol® P as cosolvent to water improved solubility and was significantly superior to all other approaches providing a sustained three-day delivery that reached therapeutic drug levels in the tissue. Solubilization in micelles or liposomes, on the contrary, did not boost delivery while micro-suspensions exhibited sedimentation on the tissue surface. Microbial contamination was responsible for considerable metabolism of the drug leading to tissue penetration of metabolites which may be relevant for therapeutic effect. Use of hydrogels under semi-occlusive conditions significantly reduced drug delivery in a viscosity-dependent fashion. Micro-rheologic analysis of the gels using diffusive wave spectroscopy confirmed the restricted diffusion of drug particles in the gel lattice which correlated with the obtained tissue delivery results. Hence, the advantages of hydrogel dressings from the applicatory characteristic point of view must be weighed against their adverse effect on drug delivery. The employed in vitro wound model was useful for the assessment of drug delivery and the development of a drug therapy concept for chronic diabetic foot ulcer. Mechanistic insights about formulation and dressing performance may be applied to drug delivery in other skin conditions such as digital ulcer.

Niacinamide: a review on dermal delivery strategies and clinical evidence.

Niacinamide, an active form of vitamin B3, is recognised for its significant dermal benefits including skin brightening, anti-ageing properties and the protection of the skin barrier. Its widespread incorporation into cosmetic products, ranging from cleansers to serums, is attributed to its safety profile and proven efficacy. Recently, topical niacinamide has also been explored for other pharmaceutical applications, including skin cancers. Therefore, a fundamental understanding of the skin permeation behaviour of niacinamide becomes crucial for formulation design. Given the paucity of a comprehensive review on this aspect, we provide insights into the mechanisms of action of topically applied niacinamide and share the current strategies used to enhance its skin permeation. This review also consolidates clinical evidence of topical niacinamide for its cosmeceutical uses and as treatment for some skin disorders, including dermatitis, acne vulgaris and actinic keratosis. We also emphasise the current exploration and perspectives on the delivery designs of topical niacinamide, highlighting the potential development of formulations focused on enhancing skin permeation, particularly for clinical benefits.

Microemulsions and Nanoemulsions for Topical Delivery of Tripeptide-3: From Design of Experiment to Anti-Sebum Efficacy on Facial Skin.

The targeted delivery of a hydrophilic Tripeptide-3 to the skin using microemulsions or nanoemulsions for facial oil reduction was the focus of this study. The impact factors affecting oil/water transparent dispersion formation, such as the surfactant system, HLB value, and co-solvent, were identified through the water titration method and pseudoternary phase diagram plots. The interfacial tension between caprylic/capric triglyceride (CCT oil) and water was significantly reduced by the surfactant/co-surfactant combination (Smix) of Cremophore® RH40 and a double-tails co-surfactant, polyglycerol-3-diisostearate, at an HLB of 13 together with a water-to-co-solvent (PG) ratio of 1:1. A two-level full factorial design of experiment (FFD-DoE) emphasized the independent variables of the HLB value, co-solvent, and CCT oil contents affecting the optimal compositions for micro- or nanoemulsion formation. The low-energy spontaneous emulsification of the optimized combination at a low Smix content (10%) yielded the translucent oil-in-water Tripeptide-3 nanoemulsions with an internal droplet size of 25.7 ± 1.20 nm, a narrow polydispersity index of 0.237 ± 0.129, and 70.6 ± 0.58% transmittance. The in vitro skin permeation study revealed a significantly higher skin penetration and retention of the Tripeptide-3 nanoemulsions compared to the high surfactant microemulsions and coarse emulsions. Skin irritation and oil control efficacy were evaluated in healthy volunteers before and after product application for 28 days. The obtained nanoemulsions not only decreased sebum production but also enhanced skin moisture levels. In conclusion, the meticulously designed nanoemulsions, incorporating suitable excipients, show a promising delivery system for hydrophilic peptides to control sebum overproduction in oily facial skin.

Spanlastic-laden nanogel as a plausible platform for dermal delivery of bimatoprost with superior cutaneous deposition and hair regrowth efficiency in androgenic alopecia.

Bimatoprost (BIM) is a prostaglandin F2α analogs originally approved for the treatment of glaucoma and ocular hypertension. Recent studies have highlighted its potential to boost hair growth. The objective of this investigation is to challenge the potential of spanlastics (SLs) as a surfactant-based vesicular system for promoting the cutaneous delivery of BIM for the management of alopecia. BIM-loaded spanlastics (BIM-SLs), composed of Span as the main vesicle component and Tween as the edge activator, were fabricated by ethanol injection method. The formulated BIM-SLs were optimized by 23 full factorial design. The optimized formula (F1) was characterized for entrapment efficiency, surface charge, vesicle size, and drug release after 12 h (Q12h). The optimized formula (F1) exhibited high drug entrapment efficiency (83.1 ± 2.1%), appropriate zeta potential (-19.9 ± 2.1 mV), Q12h of 71.3 ± 5.3%, and a vesicle size of 364.2 ± 15.8 nm, which favored their cutaneous accumulation. In addition, ex-vivo skin deposition studies revealed that entrapping BIM within spanlastic-based nanogel (BIM-SLG) augmented the dermal deposition of BIM, compared to naïve BIM gel. Furthermore, in vivo studies verified the efficacy of spanlastic vesicles to boost the cutaneous accumulation of BIM compared to naive BIM gel; the AUC0-12h of BIM-SLG was 888.05 ± 72.31 µg/mL.h, which was twice as high as that of naïve BIM gel (AUC0-12h 382.86 ± 41.12 µg/mL.h). Intriguingly, BIM-SLG outperforms both naïve BIM gel and commercial minoxidil formulations in stimulating hair regrowth in an androgenetic alopecia mouse model. Collectively, spanlastic vesicles might be a potential platform for promoting the dermal delivery of BIM in managing alopecia.

Minoxidil Nanosuspension-Loaded Dissolved Microneedles for Hair Regrowth.

Minoxidil (MIN) is used topically to treat alopecia. However, its low absorption limits its use, warranting a new strategy to enhance its delivery into skin layers. The objective of this study was to evaluate the dermal delivery of MIN by utilizing dissolved microneedles (MNs) loaded with MIN nanosuspension (MIN-NS) for hair regrowth. MIN-NS was prepared by the solvent-antisolvent precipitation technique. The particle size of MIN-NS was 226.7 ± 9.3 nm with a polydispersity index of 0.29 ± 0.17 and a zeta potential of -29.97 ± 1.23 mV. An optimized formulation of MIN-NS was selected, freeze-dried, and loaded into MNs fabricated with sodium carboxymethyl cellulose (Na CMC) polymeric solutions (MIN-NS-loaded MNs). MNs were evaluated for morphology, dissolution rate, skin insertion, drug content, mechanical properties, ex vivo permeation, in vivo, and stability studies. MNs, prepared with 14% Na CMC, were able to withstand a compression force of 32 N for 30 s, penetrate Parafilm M® sheet at a depth of 374-504 µm, and dissolve completely in the skin within 30 min with MIN %recovery of 95.1 ± 6.5%. The release of MIN from MIN-NS-loaded MNs was controlled for 24 h. MIN-NS-loaded MNs were able to maintain their mechanical properties and chemical stability for 4 weeks, when kept at different storage conditions. The in vivo study of the freeze-dried MIN-NS and MIN-NS-loaded MNs proved hair regrowth on rat skin after 11 and 7 days, respectively. These results showed that MIN-NS-loaded MNs could potentially improve the dermal delivery of MIN through the skin to treat alopecia.

Imiquimod nanocrystal-loaded dissolving microneedles prepared by DLP printing.

The utilization of 3D printing- digital light processing (DLP) technique, for the direct fabrication of microneedles encounters the problem of drug solubility in printing resin, especially if it is predominantly composed of water. The possible solution how to ensure ideal belonging of drug and water-based printing resin is its pre-formulation in nanosuspension such as nanocrystals. This study investigates the feasibility of this approach on a resin containing nanocrystals of imiquimod (IMQ), an active used in (pre)cancerous skin conditions, well known for its problematic solubility and bioavailability. The resin blend of polyethylene glycol diacrylate and N-vinylpyrrolidone, and lithium phenyl-2,4,6-trimethylbenzoylphosphinate as a photoinitiator, was used, mixed with IMQ nanocrystals in water. The final microneedle-patches had 36 cylindrical microneedles arranged in a square grid, measuring approximately 600 µm in height and 500 µm in diameter. They contained 5wt% IMQ, which is equivalent to a commercially available cream. The homogeneity of IMQ distribution in the matrix was higher for nanocrystals compared to usual crystalline form. The release of IMQ from the patches was determined ex vivo in natural skin and revealed a 48% increase in efficacy for nanocrystal formulations compared to the crystalline form of IMQ.

Formulation and Optimization of Solid Lipid Nanoparticle-based Gel for Dermal Delivery of Linezolid using Taguchi Design.

BACKGROUND: Linezolid (LNZ) is a synthetic oxazolidinone antibiotic approved for the treatment of uncomplicated and complicated skin and soft tissue infections caused by gram-positive bacteria. Typically, LNZ is administered orally or intravenously in most cases. However, prolonged therapy is associated with various side effects and lifethreatening complications. Cutaneous application of LNZ will assist in reducing the dose, hence minimizing the unwanted side/adverse effects associated with oral administration. Dermal delivery provides an alternative route of administration, facilitating a local and sustained concentration of the antimicrobial at the site of infection. OBJECTIVE: The current research work aimed to formulate solid lipid nanoparticles (SLNs) based gel for dermal delivery of LNZ in the management of uncomplicated skin and soft tissue infections to maximise its benefits and minimise the side effects. METHODS: SLNs were prepared by high-shear homogenisation and ultrasound method using Dynasan 114 as solid lipid and Pluronic F-68 as surfactant. The effect of surfactant concentration, drug-to-lipid ratio, and sonication time was investigated on particle size, zeta potential, and entrapment efficiency using the Taguchi design. The main effect plot of means and signal-to-noise ratio were generated to determine the optimized formulation. The optimized batch was formulated into a gel, and ex vivo permeation study, in vitro and in vivo antibacterial activity were conducted. RESULTS: The optimised process parameters to achieve results were 2% surfactant concentration, a drug-to-lipid ratio of 1:2, and 360 s of sonication time. The optimized batch was 206.3± 0.17nm in size with a surface charge of -24.4± 4.67mV and entrapment efficiency of 80.90 ± 0.45%. SLN-based gel demonstrated anomalous transport with an 85.43% in vitro drug release. The gel showed a 5.03 ± 0.15 cm zone of inhibition while evaluated for in vitro antibacterial activity against Staphylococcus aureus. Ex vivo skin permeation studies demonstrated 20.308% drug permeation and 54.96% cutaneous deposition. In-vivo results showed a significant reduction in colony-forming units in the group treated with LNZ SLN-based gel. CONCLUSION: Ex vivo studies ascertain the presence of the drug at the desired site and improve therapy. In vivo results demonstrated the ability of SLN-based gel to significantly reduce the number of bacteria in the stripped infection model. The utilization of SLN as an LNZ carrier holds significant promise in dermal delivery.

Enhancing Skin Delivery and Stability of Vanillic and Ferulic Acids in Aqueous Enzymatically Extracted Glutinous Rice Husk by Nanostructured Lipid Carriers.

The present study aimed to develop nanostructured lipid carriers (NLCs) and evaluate their effectiveness in enhancing the delivery and stability of vanillic and ferulic acid in the aqueous enzymatic extract of glutinous rice husk using a 0.5% w/w cellulase solution (CE0.5). NLCs were developed using a high-pressure homogenization technique and characterized for their particle size, polydispersity index, and zeta potential. The entrapment efficiency, physical and chemical stability, release profile, skin permeation, and skin retention of the NLCs loaded with CE0.5 were evaluated. It was observed that NLCs with high entrapment efficiencies efficiently encapsulate and protect both vanillic and ferulic acid, in contrast to a solution. The controlled and sustained release profile of vanillic acid and ferulic acid from NLCs suggests their potential for prolonged and targeted delivery. The findings also demonstrate the superior skin retention capabilities of NLCs without permeation compared to the solution. Notably, NLC2 exhibited the highest delivery into the skin layer, which can be attributed to its smaller particle size (107.3 ± 1.3 nm), enabling enhanced skin penetration. This research highlights the promising application of NLCs in enhancing the delivery and stability of bioactive compounds in cosmetic formulations and related fields.

Bentonite- and Palygorskite-Based Gels for Topical Drug Delivery Applications.

Bentonite or palygorskite-based hydrogels have recently been suggested as a strategy to increase bioavailability and control the retention and release of therapeutic candidates. In this work, clay-based hydrogels loaded with diclofenac acid nanocrystals have been successfully designed and developed. The aim was to improve diclofenac solubility, its dissolution rate and to enhance its local bioavailability after topical application. For this purpose, diclofenac acid nanocrystals were prepared by wet media milling technology and then loaded into inorganic hydrogels based on bentonite and/or palygorskite. Diclofenac acid nanocrystals were characterized by morphology, size, and zeta potential. Moreover, rheological behavior, morphology, solid state, release studies, and in vitro skin penetration/permeation of diclofenac acid nanocrystals-loaded hydrogels were performed. The hydrogels were characterized by a crystalline structure, and demonstrated that the inclusion of diclofenac in clay-based hydrogels resulted in an increased thermal stability. The presence of both palygorskite and bentonite reduced nanocrystal mobility, and consequently its release and penetration into the skin. On the other hand, bentonite- or palygorskite-based hydrogels revealed great potential as an alternative strategy to enhance topical bioavailability of DCF nanocrystals, enhancing their penetration to the deeper skin layers.

Altered Skin Permeation of Finasteride Using Clove Oil, Urea, and Lyophilized Powder of Grape Seed Extract.

Purpose: Finasteride is a 5-alpha reductase inhibitor used to treat hair loss and acne. The skin permeation of finasteride is one of the main challenges associated with dermal drug delivery. One way to overcome the skin barrier is to use penetration enhancers. The purpose of this study was to investigate the effect of some penetration enhancers on finasteride permeability on the skin, as well as the effect of pretreatment time on their efficacy. Methods: In order to determine the effect of penetration enhancers on the skin permeability of finasteride, the skin was exposed to clove oil, urea, and lyophilized powder of grape seed extract (LPGSE) at different pretreatment times (2, 4 h), and then the permeability parameters were determined by passing the drug through the skin. Results: The results of this study showed that clove oil, urea, and LPGSE increased the transfer of finasteride from the skin. The highest rate of permeation was observed with clove oil (4 h), and the least permeability was observed with urea (4 h). Conclusion: Increasing the pretreatment time with clove oil and LPGSE increases the permeability of finasteride. Meanwhile, the increase in pretreatment time with urea reduces the penetration of finasteride from the skin due to reversible effects.

Cannabidiol-Loaded Nanostructured Lipid Carriers (NLCs) for Dermal Delivery: Enhancement of Photostability, Cell Viability, and Anti-Inflammatory Activity.

The aim of this study was to encapsulate cannabidiol (CBD) extract in nanostructured lipid carriers (NLCs) to improve the chemical stability and anti-inflammatory activity of CBD for dermal delivery. CBD-loaded NLCs (CBD-NLCs) were prepared using cetyl palmitate (CP) as a solid lipid and stabilized with Tego® Care 450 (TG450) or poloxamer 188 (P188) by high-pressure homogenization (HPH). The CBD extract was loaded at 1% w/w. Three different oils were employed to produce CBD-NLCs, including Transcutol® P, medium-chain triglycerides (MCT), and oleic acid (OA). CBD-NLCs were successfully prepared with an entrapment efficiency (E.E.) of 100%. All formulations showed particle sizes between 160 and 200 nm with PDIs less than 0.10. The type of surfactant and oil used affected the particle sizes, zeta potential, and crystallinity of the CBD-NLCs. CBD-NLCs stabilized with TG450 showed higher crystallinity after production and storage at 30 °C for 30 days as compared to those with P188. Encapsulation of the CBD extract in NLCs enhanced its chemical stability after exposure to simulated sunlight (1000 kJ/m2) compared to that of the CBD extract in ethanolic solution. The CBD-NLCs prepared from MCT and OA showed slower CBD release compared with that from Transcutol® P, and the kinetic data for release of CBD from CBD-NLCs followed Higuchi's release model with a high coefficient of determination (>0.95). The extent of CBD permeation through Strat-M® depended on the oil type. The cytotoxicity of the CBD extract on HaCaT and HDF cells was reduced by encapsulation in the NLCs. The anti-inflammatory activity of the CBD extract in RAW264.7 cell macrophages was enhanced by encapsulation in CBD-NLCs prepared from MCT and OA.

Current Advances in Lipid Nanosystems Intended for Topical and Transdermal Drug Delivery Applications.

Skin delivery is an exciting and challenging field. It is a promising approach for effective drug delivery due to its ease of administration, ease of handling, high flexibility, controlled release, prolonged therapeutic effect, adaptability, and many other advantages. The main associated challenge, however, is low skin permeability. The skin is a healthy barrier that serves as the body's primary defence mechanism against foreign particles. New advances in skin delivery (both topical and transdermal) depend on overcoming the challenges associated with drug molecule permeation and skin irritation. These limitations can be overcome by employing new approaches such as lipid nanosystems. Due to their advantages (such as easy scaling, low cost, and remarkable stability) these systems have attracted interest from the scientific community. However, for a successful formulation, several factors including particle size, surface charge, components, etc. have to be understood and controlled. This review provided a brief overview of the structure of the skin as well as the different pathways of nanoparticle penetration. In addition, the main factors influencing the penetration of nanoparticles have been highlighted. Applications of lipid nanosystems for dermal and transdermal delivery, as well as regulatory aspects, were critically discussed.

Development of SEDDS formulation containing caffeine for dermal delivery.

OBJECTIVE: The objective of this work was to develop a self-emulsifying drug delivery system (SEDDS) containing caffeine for the treatment of cellulite. METHODS: SEDDS were prepared using the solution method. 0.5% (w/v) caffeine was added to the previously selected excipients. The system was characterized by droplet size, zeta potential, emulsification time and long-term stability. In vitro release and skin permeation were investigated using Franz-type diffusion cells. The cytotoxicity was evaluated on normal human keratinocytes. RESULTS: Caffeine SEDDS were thermodynamically stable, with a zeta potential less than - 22 mV and droplet size around 30 nm, and were long-term stable. The permeation study showed that the formulation promoted caffeine accumulation in the skin layers, suggesting an increase in local circulation. Cytotoxicity studies on HaCaT cells were not conclusive as the surfactant used indicated false-positive results due to its high molar mass. CONCLUSION: It was possible to obtain a stable SEDDS that could cause an increase in blood flow in the applied area, resulting in cellulite reduction.

OBJECTIF: L'objectif de ce travail était de développer un système d'administration de médicaments auto-émulsifiants (SEDDS) contenant de la caféine pour le traitement de la cellulite. MÉTHODES: Les SEDDS ont été préparés par la méthode en solution. 0,5 % (p/v) de caféine a été ajouté aux excipients préalablement sélectionnés. Le système a été caractérisé par la taille des gouttelettes, le potentiel zêta, le temps d'émulsification et la stabilité à long terme. La libération in vitro et la perméation cutanée ont été étudiées dans des cellules de diffusion de type Franz. La cytotoxicité était évaluée sur des kératinocytes humains normaux. RÉSULTATS: Les SEDDS de caféine étaient thermodynamiquement stables, avec un potentiel Zeta inférieur à -22 mV et une taille de gouttelettes d'environ 30 nm, et stables à long terme. L'étude de perméation a montré que les formulations favorisent l'accumulation de caféine dans les couches de la peau, suggérant une augmentation de la circulation locale. Les études de cytotoxicité sur les cellules HaCaT n'ont pas été concluantes car le surfactant utilisé indique des résultats faussement positifs dus à une masse molaire élevée. CONCLUSION: Il a été possible d'obtenir un SEDDS stable qui peut provoquer une augmentation du flux sanguin dans la zone appliquée, entraînant une réduction de la cellulite.

Formulation and development of novel lipid-based combinatorial advanced nanoformulation for effective treatment of non-melanoma skin cancer.

Non-melanoma skin cancer is one of the most common malignancies reported with high number of morbidities, demanding an advanced treatment option with superior chemotherapeutic effects. Due to high degree of drug resistance, conventional therapy fails to meet the desired therapeutic efficacy. To break the bottleneck, nanoparticles have been used as next generation vehicles that facilitate the efficient interaction with the cancer cells. Here, we developed combined therapy of 5-fluorouracil (5-FU) and cannabidiol (CBD)-loaded nanostructured lipid carrier gel (FU-CBD-NLCs gel). The NLCs were optimized using central composite design that showed an average particle size of 206 nm and a zeta potential of -34 mV. In addition, in vitro and ex vivo drug permeations studies demonstrated the effective delivery of both drugs in the skin layers via lipid structured nanocarriers. Also, the prepared FU-CBD-NLCs showed promising effect in-vitro cell studies including MTT assays, wound healing and cell cycle as compared to the conventional formulation. Moreover, dermatokinetic studies shows there was superior deposition of drugs at epidermal and the dermal layer when treated with FU-CBD-NLCs. In the end, overall study offered a novel combinatorial chemotherapy that could be an option for the treatment of non-melanoma skin cancer.

Efficacy of mesenchymal stem cell-delivery using perpendicular multi-needle injections to the skin: Evaluation of post-ejection cellular health and dermal delivery.

AIM: Mesenchymal stem cell (MSC)-therapy is increasingly being evaluated in clinical trials. Dermal delivery is not only time consuming but also unreliable, potentially hampering the therapeutic result. Therefore, qualification of cell delivery protocols is essential. This study evaluated a clinically relevant automated multi-needle injection method for cutaneous MSC-therapy, allowing the skin to be readily and timely treated, by assessing both the cellular health post-ejection and dermal delivery. METHODS: Following dispensation through the injector (31 G needles: 9- or 5-pin) the cellular health and potency (perceived- and long-term (12 h) viability, recovery, metabolism, adherence, proliferation and IDO1-expression) of adipose-derived stem cells (10-20-50 ×106 cells/ml) were assessed in vitro in addition to dermal delivery of solution in human skin. RESULTS: No significant detrimental effect on the perceived cell viability, recovery, metabolism, adherence or IDO1-expression of either cell concentration was observed. However, the overall long-term viability and proliferation decreased significantly regardless of cell concentration, nonetheless marginally. An injection depth above 1.0 mm resulted in all needles piercing the skin with dermal delivery from up to 89% needles and minimal reflux to the skin surface, and the results were confirmed by ultrasound and histology. CONCLUSION: The automated injector is capable of delivering dermal cell-doses with an acceptable cell quality.

Full factorial design, physicochemical characterization, ex vivo investigation, and biological assessment of glutathione-loaded solid lipid nanoparticles for topical application.

l-Glutathione (GSH) has exceptional antioxidant activities against UVA irradiation-induced oxidative stress and is used widely for combatting skin ageing. However, topical administration of GSH is challenging due to its inability to penetrate the stratum corneum (SC). This study aims to evaluate the solid lipid nanoparticles (SLNs) carrier system for improving the skin penetration and stability of GSH. The GSH-loaded SLNs (GSH-SLNs) were prepared by the double emulsion technique and were optimized by a full factorial design. The optimized GSH-SLNs formulation had a mean particle size of 305 ± 0.6 nm and a zeta potential of + 20.1 ± 9.5 mV, suitable for topical delivery. The ex-vivo penetration study using human skin demonstrated a 3.7-fold improvement of GSH penetration across SC with GSH-SLNs when compared with aqueous GSH. GSH-SLNs prolonged antioxidant activity on UVA irradiated fibroblast cells when compared to GSH solution, preventing UVA-induced cell death and promoting cell growth for times over 48 h. This research has illustrated that as a carrier system, SLNs were able to enhance the physicochemical stability, skin penetration, and drug deposition in the viable epidermis and dermis layers of the skin for GSH, while also maintaining the ability to protect human skin fibroblast cells against oxidative stress caused by UVA irradiation. This delivery system shows future promise as a topical delivery platform for the topical delivery of GSH and other chemically similar bioactive compounds for improving skin health.