Newer Therapies in Dermatophytosis.

With the advent of newer drugs and formulations, the armamentarium to combat dermatophytosis is ever-expanding. However, we must be rational and scientific when choosing the drugs. This review is an attempt to summarise the recently approved and upcoming therapeutic options for dermatophytosis.

A study on the applicability of one-step vortex extraction and purification combined with gas chromatography-tandem mass spectrometry for analysis of four skin penetration enhancers in cosmetics.

Based on one-step vortex extraction and purification combined with gas chromatography-tandem mass spectrometry (GC-MS/MS), we established a simple, rapid, and efficient method for the simultaneous determination of four skin penetration enhancers in cosmetics, including isosorbide dimethyl ether, isopropyl myristate, N-butylsaccharin and Azone. The extraction procedure was performed in a centrifuge tube, allowing extraction and purification in a single step. The cosmetic sample was extracted by n-hexane-ethyl acetate (1:1, V/V), purified by silica gel and anhydrous magnesium sulfate as the solid phase purification agent, separated on a TG-5 ms column (30.0 m × 0.25 mm × 0.25 µ m), confirmed and detected by GC-MS/MS in the selected reaction monitoring (SRM) mode, and quantified by the internal standard method with Di-n­butyl phthalate-D4(DBP-D4) as the internal standard. The selections of a column, extraction solvent, and solid phase purification agent were optimized. Under the optimized conditions, the four skin penetration enhancers showed good linearities in the range of 0.02∼0.50 mg L - 1. The correlation coefficients (r) were 0.992 ∼ 0.997, exceeding the specifications requirements (r ≥ 0.990); The detection (LODs, S/N = 3) and quantification limits (LOQs, S/N = 10) of the method were 0.08 ∼ 0.12 mg kg-1 and 0.25 ∼ 0.40 mg kg-1, respectively. According to the cosmetic matrix in different formulation systems, the spiked recovery tests were carried out at three levels, i.e., low, medium, and high. The average recoveries of the analytes were 85.3% ∼ 95.6%, and the relative standard deviations (RSDs, n = 6) were 2.1% ∼ 7.8%. The established method was also employed to analyze cosmetics in the market. Azone, isosorbide dimethyl ether, and isopropyl myristate resulted as the most widely used skin penetration enhancers in cosmetics. The method established in this study has the advantages of operational simplicity, high sensitivity, good reproducibility, and low consumption of samples and solvents. Moreover, it can be used to determine skin penetration enhancers in cosmetics.

Control of cell penetration enhancer shielding and endosomal escape-kinetics crucial for efficient and biocompatible siRNA delivery.

Although cationic liposomes are efficient carriers for nucleic acid delivery, their toxicity often hampers the clinical translation. Polyethylene glycol (PEG) coating has been largely used to improve their stability and reduce toxicity. Nevertheless, it has been found to decrease the transfection process. In order to exploit the advantages of cationic liposomes and PEG decoration for nucleic acid delivery, liposomes decorated with tetraArg-[G-1]-distearoyl glycerol (Arg4-DAG) dendronic oligo-cationic lipid enhancer (OCE) and PEG-lipid have been investigated. Non decorated or OCE-decorated lipoplexes (OCEfree-LPX and OCE-LPX, respectively) were obtained by lipid film hydration using oligonucleotide (ON) solutions. PEG and OCE/PEG decorated lipoplexes (PEG-OCEfree-LPX and PEG-OCE-LPX, respectively) were obtained by post-insertion of 2 or 5 kDa PEG-DSPE on preformed lipoplexes. The OCE decoration yielded lipoplexes with size of about 240 nm, 84% loading efficiency at 10 N/P ratio, ten times higher than OCEfree-LPX, and prevented the ON release when incubated with physiological heparin concentration or with plasma. The PEG decoration reduced the zeta potential, enhanced the lipoplex stability in serum and decreased both hemolysis and cytotoxicity, while it did not affect the lipoplex size and ON loading. With respect to OCEfree-LPX, the OCE-LPX remarkably associated with cells and were taken up by different cancer cell lines (HeLa and MDA-MB-231). Interestingly, 2 or 5 kDa PEG decoration did not reduce either the cell interaction or the cell up-take of the cationic lipoplexes. With siRNA as a payload, OCE enabled efficient internalization, but endosomal release was hampered. Post-transfection treatment with the lysosomotropic drug chloroquine allowed to identify the optimal time point for endosomal escape. Chloroquine treatment after 12 to 20 h of LPX pre-incubation enabled siRNA mediated target knockdown indicating that this is the time window of endo-lysosomal processing. This indicates that OCE can protect siRNA from lysosomal degradation for up to 20 h, as shown by these rescue experiments.

Improving the efficacy of photodynamic therapy for actinic keratosis: A comprehensive review of pharmacological pretreatment strategies.

BACKGROUND: Photodynamic therapy (PDT) is approved for treatment of actinic keratoses (AKs) and field-cancerisation. Pretreatment with pharmacological compounds holds potential to improve PDT efficacy, through direct interaction with PpIX formation or through an independent response, both of which may improve PDT treatment. OBJECTIVE: To present the currently available clinical evidence of pharmacological pretreatments prior to PDT and to associate potential clinical benefits with the pharmacological mechanisms of action of the individual compounds. METHODS: A comprehensive search on the Embase, MEDLINE, and Web of Science databases was performed. RESULTS: In total, 16 studies investigated 6 pretreatment compounds: 5-fluorouracil (5-FU), diclofenac, retinoids, salicylic acid, urea, and vitamin D. Two of these, 5-FU and vitamin D, robustly increased the efficacy of PDT across multiple studies, illustrated by mean increases in clearance rates of 21.88% and 12.4%, respectively. Regarding their mechanisms, 5-FU and vitamin D both increased PpIX accumulation, while 5-FU also induced a separate anticarcinogenic response. Pretreatment with diclofenac for four weeks improved the clearance rate in one study (24.9%), administration of retinoids had a significant effect in one of two studies (16.25%), while salicylic acid and urea did not lead to improved PDT efficacy. Diclofenac and retinoids demonstrated independent cytotoxic responses, whereas salicylic acid and urea acted as penetration enhancers to increase PpIX formation. CONCLUSION: 5-FU and vitamin D are well-tested, promising candidates for pharmacological pretreatment prior to PDT. Both compounds affect the haem biosynthesis, providing a target for potential pretreatment candidates. KEY WORDS: Photodynamic Therapy, Actinic Keratosis,Pre-tretment,Review,enhancement.

Localized Drug Delivery Systems: An Update on Treatment Options for Head and Neck Squamous Cell Carcinomas.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers in the world, with surgery, radiotherapy, chemotherapy, and immunotherapy being the primary treatment modalities. The treatment for HNSCC has evolved over time, due to which the prognosis has improved drastically. Despite the varied treatment options, major challenges persist. HNSCC chemotherapeutic and immunotherapeutic drugs are usually administered systemically, which could affect the patient's quality of life due to the associated side effects. Moreover, the systemic administration of salivary stimulating agents for the treatment of radiation-induced xerostomia is associated with toxicities. Localized drug delivery systems (LDDS) are gaining importance, as they have the potential to provide non-invasive, patient-friendly alternatives to cancer therapy with reduced dose-limiting toxicities. LDDSs involve directly delivering a drug to the tissue or organ affected by the disease. Some of the common localized routes of administration include the transdermal and transmucosal drug delivery system (DDSs). This review will attempt to explore the different treatment options using LDDSs for the treatment of HNSCC and radiotherapy-induced damage and their potential to provide a better experience for patients, as well as the obstacles that need to be addressed to render them successful.

Natural Ingredients of Transdermal Drug Delivery Systems as Permeation Enhancers of Active Substances through the Stratum Corneum.

In recent years, significant progress has been made in transdermal drug delivery systems, but there is still a search for enhancers that can improve the absorption of active substances through the stratum corneum. Although permeation enhancers have been described in the scientific literature, the use of naturally occurring substances in this role is still of particular interest, because they can offer a high level of safety of use, with a low risk of skin irritation, and high efficiency. In addition, these ingredients are biodegradable, easily available, and widely accepted by consumers due to the growing trust in natural compounds. This article provides information on the role of naturally derived compounds in transdermal drug delivery systems that help them penetrate the skin. The work focuses on the components found in the stratum corneum such as sterols, ceramides, oleic acid, and urea. Penetration enhancers found in nature, mainly in plants, such as terpenes, polysaccharides, and fatty acids have also been described. The mechanism of action of permeation enhancers in the stratum corneum is discussed, and information on the methods of assessing their penetration efficiency is provided. Our review mainly covers original papers from 2017 to 2022, supplemented with review papers, and then older publications used to supplement or verify the data. The use of natural penetration enhancers has been shown to increase the transport of active ingredients through the stratum corneum and can compete with synthetic counterparts.

Biomaterial-based delivery platforms for transdermal immunotherapy.

Nowadays, immunotherapy is one of the most essential treatments for various diseases and a broad spectrum of disorders are assumed to be treated by altering the function of the immune system. For this reason, immunotherapy has attracted a great deal of attention and numerous studies on different approaches for immunotherapies have been investigated, using multiple biomaterials and carriers, from nanoparticles (NPs) to microneedles (MNs). In this review, the immunotherapy strategies, biomaterials, devices, and diseases supposed to be treated by immunotherapeutic strategies are reviewed. Several transdermal therapeutic methods, including semisolids, skin patches, chemical, and physical skin penetration enhancers, are discussed. MNs are the most frequent devices implemented in transdermal immunotherapy of cancers (e.g., melanoma, squamous cell carcinoma, cervical, and breast cancer), infectious (e.g., COVID-19), allergic and autoimmune disorders (e.g., Duchenne's muscular dystrophy and Pollinosis). The biomaterials used in transdermal immunotherapy vary in shape, size, and sensitivity to external stimuli (e.g., magnetic field, photo, redox, pH, thermal, and even multi-stimuli-responsive) were reported. Correspondingly, vesicle-based NPs, including niosomes, transferosomes, ethosomes, microemulsions, transfersomes, and exosomes, are also discussed. In addition, transdermal immunotherapy using vaccines has been reviewed for Ebola, Neisseria gonorrhoeae, Hepatitis B virus, Influenza virus, respiratory syncytial virus, Hand-foot-and-mouth disease, and Tetanus.

Development and Evaluation of an FDM Printed Nasal Device for CPZ Solid Nanoparticles.

Nasal drug delivery has been a focus of scientific interest for decades. A number of drug delivery systems and devices are available and have been highly successful in providing better and more comfortable therapy. The benefits of nasal drug delivery are not in question. The nasal surface provides an excellent context for the targeted delivery of active substances. In addition to the large nasal surface area and intensive absorption, the active substances delivered through the nose overcome the blood-brain barrier and can be delivered directly to the central nervous system. Formulations for nasal administration are typically solutions or liquid dispersed systems such as emulsions or suspensions. Formulation techniques for nanostructures have recently undergone intensive development. Solid-phase heterogeneous dispersed systems represent a new direction in pharmaceutical formulations. The wide range of possible examples and the variety of excipients allow for the delivery of a wide range of active ingredients. The aim of our experimental work was to develop a solid drug delivery system that possesses all of the above-mentioned advantageous properties. In developing solid nanosystems, we not only exploited the advantages of size but also the adhesive and penetration-enhancing properties of excipients. During formulation, several amphiphilic compounds with adhesion properties and penetration enhancing effects were incorporated. We used chlorpromazine (CPZ), which is mainly used in the treatment of psychotic disorders such as schizophrenia and bipolar disorder. Chlorpromazine has been previously investigated by our team in other projects. With the availability of previous methods, the analytical characterization of the drug was carried out effectively. Due to the frequent and severe side effects of the drug, the need for therapeutic dose reduction is indisputable. In this series of experiments, we succeeded in constructing drug delivery systems. Finely divided Na nanoparticles were formed using a Büchi B90 nanospray dryer. An important step in the development of the drug carrier was the selection of suitable inert carrier compounds. Particle size determination and particle size distribution analysis were performed to characterize the prepared nanostructures. As safety is the most important aspect of any drug formulation, all components and systems were tested with different biocompatibility assays. The tests performed demonstrated the safe applicability of our systems. The bioavailability of chlorpromazine was studied as a function of the ratio of the active ingredient administered nasally and intravenously. As described above, most nasal formulations are liquids, but our system is solid, so there is currently no tool available to accurately target this system. As a supplement of the project, a nasal dosing device was developed, corresponding to the anatomical structure; a prototype of the device was made using 3D FDM technology. Our results lay the foundation for the design and industrial scaling of a new approach to the design and production of a high-bioavailability nasal medicinal product.

Transdermal Delivery of Insulin Using Combination of Iontophoresis and Deep Eutectic Solvents as Chemical Penetration Enhancers: In Vitro and in Vivo Evaluations.

A serious challenge in transdermal iontophoresis (IP) delivery of insulin (INS) is the low permeability of the drug across the skin. In this paper, we introduced deep eutectic solvent (DESs) as novel chemical penetration enhancers (CPEs) for transdermal IP of INS across rat skin, both in vitro and in vivo. Three different DESs based on choline chloride (ChCl), namely, ChCl/UR (ChCl and urea), ChCl/GLY (ChCl and glycerol), and ChCl/EG (ChCl and ethylene glycol) in the 1:2 molar ratios have been prepared. To evaluate the capability of studied DESs as CPEs for IP delivery of INS, the rat skin sample was treated with each DES. The effects of different experimental parameters (current density, formulation pH, INS concentration, NaCl concentration, and treatment time) on the in vitro transdermal iontophoretic delivery of INS were investigated. The in vitro permeation studies exhibited that INS was easily delivered employing ChCl/EG, and ChCl/GLY treatments, compared with ChCl/UR: the cumulative amount of permeated INS at the end of the experiment (Q24h) was found to be 131.0, 89.4, and 29.6 µg cm-2 in the presence of ChCl/EG, ChCl/GLY, and ChCl/UR, respectively. The differences in Q24h values of INS are due to the different capabilities of the studied DESs to treat the epidermis layer of skin. In vivo experiments revealed that the blood glucose level in diabetic rats could be decreased using ChCl/EG, and ChCl/GLY as novel CPEs in the IP delivery of INS. The presented work will open new doors towards searching for novel CPEs in the development of transdermal IP of INS.

Enhanced skin penetration of Finasteride loaded DMSO-liposomes for the treatment of androgenic alopecia: comparison with conventional liposomes.

Long-term treatment with finasteride (FIN) for androgenic alopecia is restricted due to its systemic side effects. To address this problem, DMSO-modified liposomes were prepared in the present study to improve the topical delivery of FIN. DMSO-liposomes were prepared by a modification of the ethanol injection method. It was hypothesized that the permeation-enhancing property of DMSO could promote drug delivery to deeper skin layer where hair follicles are present. Liposomes were optimized by quality by design (QbD) approach and biologically evaluated in a rat model of testosterone-induced alopecia. Optimized DMSO-liposomes were spherical and had mean vesicle size, zeta potential, and entrapment efficiency of 330.1 ± 1.5, -14.52 ± 1.32, and 59.02 ± 1.12%, respectively. Biological evaluation on testosterone-induced alopecia and skin histology shows that follicular density and anagen/telogen (A/T) ratio were increased in rats treated with DMSO-liposomes as compared to FIN-liposomes without DMSO and an alcoholic solution of FIN applied topically. DMSO-liposomes could be promising skin delivery vehicles for FIN or similar drugs.

Biopolymers in Mucoadhesive Eye Drops for Treatment of Dry Eye and Allergic Conditions: Application and Perspectives.

Dry eye syndrome and allergic conjunctivitis are the most common inflammatory disorders of the eye surface. Although eye drops are the most usual prescribed dosage form, they are characterized by low ocular availability due to numerous barrier mechanisms of the eye. The use of biopolymers in liquid ophthalmic preparations has numerous advantages, such as increasing the viscosity of the tear film, exhibiting bioadhesive properties, and resisting the drainage system, leading to prolonged retention of the preparation at the site of application, and improvement of the therapeutic effect. Some mucoadhesive polymers are multifunctional excipients, so they act by different mechanisms on increasing the permeability of the cornea. Additionally, many hydrophilic biopolymers can also represent the active substances in artificial tear preparations, due to their lubrication and moisturizing effect. With the modification of conventional ophthalmic preparations, there is a need for development of new methods for their characterization. Numerous methods for the assessment of mucoadhesiveness have been suggested by the literature. This review gives an overview related to the development of mucoadhesive liquid ophthalmic formulations for the treatment of dry eye and allergic conditions.

Evaluating the Skin Interactions and Permeation of Alginate/Fucoidan Hydrogels Per Se and Associated with Different Essential Oils.

Marine polysaccharides are recognized for their biological properties and their application in the drug delivery field, favoring hydrogel-forming capacities for cutaneous application towards several dermatological conditions. Essential oils have been widely used in skin, not only for their remarkable biological properties, but also for their capacity to enhance permeation through the skin layers and to confer a pleasant scent to the formulation. In this study, menthol, L-linalool, bergamot oil, and ß-pinene were incorporated in alginate/fucoidan hydrogels to evaluate their skin permeation enhancement profile and assess their influence on the skin organization. The combinations of different essential oils with the marine-based fucoidan/alginate hydrogel matrix were characterized, resulting in formulations with pseudoplastic rheological properties favorable for a uniform application in the skin. The ex vivo Franz diffusion permeation assays revealed that calcein loaded in bergamot-alginate/fucoidan hydrogel permeated more than 15 mg out of the initial 75 mg than when in linalool-alginate/fucoidan, alginate/fucoidan or hydrogel without any incorporated oil. Skin calcein retention for menthol- and pinene-alginate/fucoidan hydrogels was 15% higher than in the other conditions. Infrared micro-spectroscopic analysis through synchrotron-based Fourier Transform Infrared Microspectroscopy evidenced a symmetric shift in CH3 groups towards higher wavenumber, indicating lipids' fluidization and less lateral packing, characterized by a band at 1468 cm-1, with the bergamot-alginate/fucoidan, which contributes to enhancing skin permeation. The study highlights the effect of the composition in the design of formulations for topical or transdermal delivery systems.

Tailoring surface properties of liposomes for dexamethasone intraocular administration.

Diseases of the posterior eye segment are often characterized by intraocular inflammation, which causes, in the long term, severe impairment of eye functions and, ultimately, vision loss. Aimed at enhancing the delivery of anti-inflammatory drugs to the posterior eye segment upon intravitreal administration, we developed liposomes with an engineered surface to control their diffusivity in the vitreous and retina association. Hydrogenated soybean phosphatidylcholine (HSPC)/cholesterol liposomes were coated with (agmatinyl)6-maltotriosyl-acetamido-N-(octadec-9-en-1-yl)hexanamide (Agm6-M-Oleate), a synthetic non-peptidic cell penetration enhancer (CPE), and/or 5% of mPEG2kDa-DSPE. The zeta potential of liposomes increased, and the mobility in bovine vitreous and colloidal stability decreased with the Agm6-M-Oleate coating concentration. Oppositely, mPEG2kDa-DSPE decreased the zeta potential of liposomes and restored both the diffusivity and the stability in vitreous. Liposomes with 5 mol% Agm6-M-Oleate coating were well tolerated by ARPE-19 retina cells either with or without mPEG2kDa-DSPE, while 10 mol% Agm6-M-Oleate showed cytotoxicity. Agm6-M-Oleate promoted the association of liposomes to ARPE-19 cells with respect to plain liposomes, while mPEG2kDa-DSPE slightly reduced the cell interaction. Dexamethasone hemisuccinate (DH) was remotely loaded into liposomes with a loading capacity of ∼10 wt/wt%. Interestingly, mPEG2kDa-DSPE coating reduced the rate of DH release and enhanced the disposition of Agm6-M-Oleate coated liposomes in the ARPE-19 cell cytosol resulting in a more efficient anti-inflammatory effect. Finally, mPEG2kDa-DSPE enhanced the association of DH-loaded Agm6-M-Oleate coated liposomes to explanted rat retina, which reflected in higher viability of inner and outer nuclear layer cells.

Formulation and Evaluation of Transdermal Patches Containing BGP-15.

BGP-15 is an active ingredient with many advantages, e.g., beneficial cardiovascular and anti-inflammatory effects. The transdermal administration of BGP-15 has great potential, which has not been investigated yet, despite the fact that it is a non-invasive and safe form of treatment. The aim of our study was to formulate transdermal patches containing BGP-15 and optimize the production with the Box-Behnken design of experiment. The most optimal formulation was further combined with penetration enhancers to improve bioavailability of the active ingredient, and the in vitro drug release and in vitro permeation of BGP-15 from the patches were investigated. FTIR spectra of BGP-15, the formulations and the components were also studied. The most optimal formulation based on the tested parameters was dried for 24 h, with 67% polyvinyl alcohol (PVA) content and low ethanol content. The selected penetration enhancer excipients were not cytotoxic on HaCaT cells. The FTIR measurements and SEM photography proved the compatibility of the active substance and the vehicle; BGP-15 was present in the polymer matrix in dissolved form. The bioavailability of BGP-15 was most significantly enhanced by the combination of Transcutol and Labrasol. The in vitro permeation study confirmed that the formulated patches successfully enabled the transdermal administration of BGP-15.

Skin Penetration Enhancer-Incorporated Lipid Nanovesicles (SPE-LNV) for Skin Brightening and Wrinkle Treatment.

In this work, we utilize skin penetration enhancers (SPEs) such as ceramide and fatty acids in lipid nanovesicles to promote the transdermal delivery of active ingredients. These SPE-incorporated lipid nanovesicles (SPE-LNV) interact with the constituents of skin's outermost stratum corneum (SC) layer, enabling even niacinamide and adenosine with high water solubility to effectively permeate through, leading to enhanced skin efficacy. We demonstrate by both in vitro and in vivo skin permeation studies that the SPE-LNV formulation containing both ceramide and fatty acids (LNV-CF) exhibits deeper penetration depth and faster permeation rate compared to conventional lipid nanovesicles (LNV) without SPE as well as LNV-C with only ceramide. Moreover, in vivo clinical trials were also performed to confirm that LNV-CF most effectively mediates the delivery of niacinamide and adenosine, resulting in a substantial decrease in melanin index as well as skin wrinkle compared to the control groups. We envision that the strategy of incorporating both ceramide and fatty acids in lipid nanovesicles offers a simple and convenient route for the rapid and effective delivery of water-soluble active ingredients across the skin barrier layer.

Sorbitan Monolaurate-Containing Liposomes Enhance Skin Cancer Cell Cytotoxicity and in Association with Microneedling Increase the Skin Penetration of 5-Fluorouracil.

Squamous cell carcinoma (SCC) represents 20% of cases of non-melanoma skin cancer, and the most common treatment is the removal of the tumor, which can leave large scars. 5-Fluorouracil (5FU) is a drug used in the treatment of SCC, but it is highly hydrophilic, resulting in poor skin penetration in topical treatment. Some strategies can be used to increase the cutaneous penetration of the drug, such as the combination of liposomes containing penetration enhancers, for instance, surfactants, associated with the use of microneedling. Thus, the present work addresses the development of liposomes with penetration enhancers, such as sorbtitan monolaurate, span 20, for topical application of 5-FU and associated or not with the use of microneedling for skin delivery. Liposomes were developed using the lipid film hydration, resulting in particle size, polydispersity index, zeta potential, and 5-FU encapsulation efficiency of 88.08 nm, 0.169, -12.3 mV, and 50.20%, respectively. The presence of span 20 in liposomes potentiated the in vitro release of 5-FU. MTT assay was employed for cytotoxicity evaluation and the IC50 values were 0.62, 30.52, and 24.65 µM for liposomes with and without span 20 and 5-FU solution, respectively after 72-h treatment. Flow cytometry and confocal microscopy analysis evidenced high cell uptake for the formulations. In skin penetration studies, a higher concentration of 5-FU was observed in the epidermis + dermis, corresponding to 1997.71, 1842.20, and 2585.49 ng/cm2 in the passive penetration and 3214.07, 2342.84, and 5018.05 ng/cm2 after pretreatment with microneedles, for solution, liposome without and with span 20, respectively. Therefore, herein, we developed a nanoformulation for 5-FU delivery, with suitable physicochemical characteristics, potent skin cancer cytotoxicity, and cellular uptake. Span 20-based liposomes increased the skin penetration of 5-FU in association of microneedling. Altogether, the results shown herein evidenced the potential of the liposome containing span 20 for topical delivery of 5-FU.

Chemical vs. Physical Methods to Improve Dermal Drug Delivery: A Case Study with Nanoemulsions and Iontophoresis.

So far, various approaches have been proposed to improve dermal drug delivery. The use of chemical penetration enhancers has a long history of application, while methods based on the electrical current (such as iontophoresis) stand out as promising "active" techniques. Aiming to evaluate the contribution of different approaches to dermal delivery, in this work curcumin-loaded nanoemulsions with and without monoterpenes (eucalyptol or pinene) as chemical penetration enhancers, and a custom-made adhesive dermal delivery system based on iontophoresis were designed and assessed. In an in vivo study applying skin bioengineering techniques, their safety profile was proven. Three examined iontophoresis protocols, with total skin exposure time of 15 min (continuous flow for 15 min (15-0); 3 min of continuous flow and 2 min pause (3-2; 5 cycles) and 5 min of continuous flow and 1 min pause (5-1; 3 cycles) were equally efficient in terms of the total amount of curcumin that penetrated through the superficial skin layers (in vivo tape stripping) (Q3-2 = 7.04 ± 3.21 µg/cm2; Q5-1 = 6.66 ± 2.11 µg/cm2; Q15-0 = 6.96 ± 3.21 µg/cm2), significantly more efficient compared to the referent nanoemulsion and monoterpene-containing nanoemulsions. Further improvement of an efficient mobile adhesive system for iontophoresis would be a practical contribution in the field of dermal drug application.

Topical Dosage Formulation of Lyophilized Philadelphus coronarius L. Leaf and Flower: Antimicrobial, Antioxidant and Anti-Inflammatory Assessment of the Plant.

Philadelphus coronarius is a versatile plant and its use in folk medicine has a long tradition; however, scientifically, the medical utilization of the herb is a less explored research field. The aim of our study was to identify and determine the quantity of the bioactive compounds of both the leaf and the flower and prepare a lyophilized product of them, from which medical ointments were formulated, since the topical application of P. coronarius has also not been studied. In vitro drug release, texture analysis and biocompatibility experiments were carried out, as well as the investigation of microbiological, antioxidant and anti-inflammatory properties. According to our results the composition and the selected excipients of the ointments have a great impact on the drug release, texture and bioavailability of the preparation. During the microbiological testing, the P. coronarius leaf was effective against Escherichia coli and Staphylococcus aureus, but it did not significantly decrease IL-4 production when it was tested on HaCaT cells. P. coronarius is a promising herb, and its topical application in antimicrobial therapy can be a useful addition to modern medical therapy.

Formulation and Evaluation of Transdermal Gel Containing Tacrolimus-Loaded Spanlastics: In Vitro, Ex Vivo and In Vivo Studies.

Our goal was to prepare Span 60-based elastic nanovesicles (spanlastics (SPLs)) of tacrolimus (TCR) using the adapted ethanol injection method, characterize them, and evaluate their ability to improve the transdermal permeation of the active substance. The impact of two different concentrations of penetration enhancers, namely, propylene glycol and oleic acid, on the entrapment efficiency, vesicle size, and zeta potential was assessed. Moreover, in vitro release through a semipermeable membrane and ex vivo penetration through hairless rat skin were performed. Morphological examination and pharmacokinetics were performed for one selected formulation (F3OA1). TCR-loaded SPLs were effectively formulated with two different concentrations of permeation enhancers, and the effect of these enhancers on their physicochemical properties differed in accordance with the concentration and kind of enhancer used. The results of in vitro release displayed a considerable (p < 0.05) enhancement compared to the suspension of the pure drug, and there was a correlation between the in vitro and ex vivo results. The selected TCR-loaded nanovesicles incorporated into a gel base showed appreciable advantages over the oral drug suspension and the TCR-loaded gel. Additionally, the pharmacokinetic parameters were significantly (p < 0.05) improved based on our findings. Moreover, the AUC0−7 ng·h/mL form F3 OA1 was 3.36-fold higher than that after the administration of the TCR oral suspension.

Influence of Vehicles and Penetration Enhancers on the Permeation of Cinnarizine Through the Skin

Objectives: The aim of this study was to determine the influence of vehicles and penetration enhancers on the penetration and permeation of cinnarizine (CNZ) through the skin. Materials and Methods: Topical formulations based on hydrogel, o/w emulsion and oleaginous cream were prepared. After determination of physical properties of formulations, the penetration and permeation of CNZ through the stratum corneum and full-thickness skin was investigated by an ex vivo study. Results: The cumulative amount of CNZ permeated from the base hydrogel formulation was about 5 times higher than the base o/w emulsion and base oleaginous cream formulations. The incorporation of penetration enhancers to the base hydrogel and o/w emulsion formulations generally increased CNZ penetration through the skin. Transcutol® was confirmed to provide the highest penetration in the hydrogel formulation. Propylene glycol was found to be the most suitable penetration enhancer for CNZ in the oleaginous cream. Glycerol and oleic acid displayed the highest effect in the o/w emulsion. Conclusion: It was concluded that the hydrogel containing Transcutol® provided the highest penetration through the skin among all formulations and this formulation could be an alternative to the oral route in the treatment of Ménière's disease and motion sickness. Thus, the risk of systemic side effects caused by oral medication can be reduced or eliminated.