UNASSIGNED: Famciclovir, the drug of choice for cold sores and recurrent genital herpes, has poor oral bioavailability and is associated with numerous side effects. The study aimed to explore the possibility of transdermal application of famciclovir through a transferosome-loaded gelling system to localize the drug at the site of application with improved penetrability, therapeutic effects, and comfort.
UNASSIGNED: Transferosomes of famciclovir were prepared using tween 80, phospholipid, and cholesterol. To optimize drug entrapment and the vesicular size of the transferosomes, a central composite design was employed. The optimized formulation was evaluated for physicochemical characteristics, surface morphology, and degree of deformability. The optimized product was included in the Carbopol 940 gelling system. The gel was evaluated for ex vivo permeation, skin irritation, drug deposition at various skin layers, and histopathological analysis.
UNASSIGNED: The design optimization yielded an optimized product (FAMOPT) of nanosized (339 nm) stable vesicles of the transferosome of famciclovir. The surface morphology analysis revealed the formation of nanovesicles without aggregation. Compatibility between the drug and excipients was established. The elasticity of the vesicles demonstrated resistance to leakage. The permeation of the drug was enhanced by 2.8 times. The gel was found to be non-irritating and non-sensitizing to the animal skin. The drug deposition at various skin layers was remarkably improved, indicating effective drug penetration. The histopathological examination further demonstrated the penetration of nano-vesiculate drugs through deeper layers of the skin.
UNASSIGNED: Hence, nano-vesicular famciclovir delivery is a promising alternative to conventional famciclovir delivery with enhanced local and systemic action for herpes treatment.

Nanoemulsions have carved their position in topical delivery owing to their peculiar features of forming a uniform film on the skin and conquering stratum corneum barrier and hence fostering dermal penetration and retention. The present work developed syringic acid nanoemulsion (SA-NE) by spontaneous emulsification as an anti-psoriatic remedy via the dermal route. SA-NE were prepared with either lauroglycol90, limonene or their combination (oil phase) and tween80 (surfactant) with variable concentrations. The physicochemical characteristics of SA-NE were assessed together with Ex-vivo skin deposition and dermal toxicity. The effectiveness of optimal formula in psoriatic animal model and psoriatic patients was investigated using PASI scoring and dermoscope examination. Results showed that, SA-NE containing mixture of lauroglycol 90, limonene and 10 % tween80 (F5), was selected as the optimal formula presenting stable nanoemulsion for 2-month period, showing droplet size of 177.6 ± 13.23 nm, polydispersity index of 0.16 ± 0.06, zeta potential of -21.23 ± 0.41 mV. High SA% in different skin strata and no dermal irritation was noticed with limonene-based SA-NE also it showed high in-vitro anti- inflammatory potential compared to the blank and control formulations. A preclinical study demonstrated that limonene-based SA-NE is effective in alleviating psoriasis-like skin lesions against imiquimod-induced psoriasis in rats. Clinically, promising anti-psoriatic potential was asserted as all patients receiving F5 experienced better clinical improvement and response to therapy, achieving ≥ 50 % reduction in PASI scores versus only 35 % responders in the Dermovate® cream group. Collectively, the practical feasibility of limonene-based SA-NE topical delivery can boost curative functionality in the treatment of psoriatic lesions.

To investigate the effect of retinoids, such as retinol (ROL), retinal (RAL), and retinyl palmitate (RP), on epidermal integrity, skin deposition, and bioconversion to retinoic acid (RA). 3-D human skin equivalent model (EpiDermFT™) was used. Epidermal cellular integrity measured by TEER values was significantly higher for a topical treatment of ROL and RAL than RP (p < 0.05). The skin deposition (μM) of ROL and RAL was approximately 269.54 ± 73.94 and 211.35 ± 20.96, respectively, greater than that of RP (63.70 ± 37.97) over 2 h incubation. Spectral changes were revealed that the CO maximum absorbance occurred between 1600∼1800 cm-1 and was greater from ROL than that from RAL and RP, indicating conjugation of R-OH to R-CHO or R-COOH could strongly occur after ROL treatment. Subsequently, a metabolite from the bioconversion of ROL and RAL was identified as RA, which has a product ion of m/z 283.06, by using liquid a chromatography-mass spectrometry (LC-MS) - total ion chromatogram (TIC). The amount of bioconversion from ROL and RAL to RA in artificial skin was 0.68 ± 0.13 and 0.70 ± 0.10 μM at 2 h and 0.60 ± 0.04 and 0.57 ± 0.06 μM at 24 h, respectively. RA was not detected in the skin and the receiver compartment after RP treatment. ROL could be a useful dermatological ingredient to maintain epidermal integrity more effectively, more stably deposit on the skin, and more steadily metabolize to RA than other retinoids such as RAL and RP.

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.

The purposes of current study were to investigate the effect of ginsenosides from BIOGF1K enriched in compound K (CK) and compound Y (CY) on the skin barrier function, the deposition in in vitro 3-D human tissue model (EpiDermFT™ Full Thickness 400), and to identify and quantify kinetic bioconversion of the ginsenosides in artificial skin by utilizing the Fourier transform infrared spectroscopy (FT-IR) and liquid chromatography mass spectrometry (LC-MS), respectively. Epidermal barrier integrity evaluated using transepithelial electrical resistance (TEER) was significantly higher in the BIOGF1K treatment than the CY or CK individual treatment throughout incubation (p < 0.05). Skin deposition (%) of CY and CK from BIOGF1K treatment was approximately 4 and 2 times higher than the CY and CK single component treatment, respectively. Total amount of CK found in human skin by deposition and bioconversion was approximately 1087.3, 528.82, and 867.76 μM after topical treatment of BIOGF1K, CK, and CY. Results from the current study reveal that topical treatment of BIOGF1K more effectively induced CK deposition as well as bioconversion of CY to CK than that of a single treatment of CY or CK, suggesting that BIOGF1K could be a useful cosmetic preparation for enhancing skin function.

A hydrogel topical patch of neomycin was developed by using sodium alginate (SA) and hydroxyethylcellulose (HEC) as polymers. Free radical polymerization in an aqueous medium was initiated by using acrylic acid (AA) and N,N\'-methylenebisacrylamide (MBA). Prepared hydrogels were characterized for pH sensitivity and sol-gel analysis. In addition, the effect of reactant contents on the developed formulation was evaluated by swelling behavior. SEM assay showed the rough structure of the hydrogel-based polymeric matrix, which directly enhances the ability to uptake fluid. FTIR spectra revealed the formation of a new polymeric network between reactant contents. TGA and DSC verified that fabricated polymeric patches were more thermodynamically stable than pure components. Gel fractions increased with increases in polymer, monomer, and cross-linker contents. The swelling study showed the pH-dependent swelling behavior of patches at pH 5.5, 6.5, and 7.4. The release pattern of the drug followed zero-order kinetics, with diffusion-controlled drug release patterns according to the Korsmeyer-Peppas (KP) model. Ex vivo studies across excised rabbit skin verified the drug retention in the skin layers. The hydrogel patch effectively healed the wounds produced on the rabbit skin, whereas the formulation showed no sign of irritation on intact skin. Therefore, neomycin hydrogel patches can be a potential candidate for controlled delivery for efficient wound healing.

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.

The largest organ of the body provides the main challenge for the transdermal delivery of lipophilic or high molecular weight drugs. To cross the main barrier of the skin, the stratum corneum, many techniques have been developed and improved. In the last 20 years, the association of microneedles with nanostructured systems has gained prominence for its versatility and for enabling targeted drug delivery. Currently, the combination of these mechanisms is pointed to as an emerging technology; however, some gaps need to be answered to transcend the development of these devices from the laboratory scale to the pharmaceutical market. It is known that the lack of regulatory guidelines for quality control is a hindrance to market conquest. In this context, this study undertakes a scoping review of original papers concerning methods applied to evaluate both the quality and drug/protein delivery of dissolving and hydrogel-forming microneedles developed in association with nanostructured systems.

Some chemicals have been reported to cause metabolite-related phototoxicity, and this study aimed to verify the applicability of photosafety assessment based on photochemical and pharmacokinetic properties to evaluate the metabolite-related phototoxicity risk. The phototoxic risk of imipramine (IMI) and its metabolite, desipramine (DMI), was evaluated by photochemical and pharmacokinetic analyses. IMI and DMI were found to have similar photoreactivities based on the generation of reactive oxygen species. The skin concentrations of IMI and DMI reached maximal levels at approximately 1 and 4 h, respectively, after oral administration of IMI (10 mg/kg), and DMI showed high skin deposition compared with IMI. According to the results, DMI was identified as a contributor to phototoxicity induced by orally-taken IMI. In in vivo phototoxicity testing, ultraviolet A irradiation from 3 to 6 h after oral administration of IMI (100 mg/kg) caused more potent phototoxic reactions compared with that from 0 to 3 h, and DMI yielded by metabolism of IMI would be associated with phototoxic reactions caused by orally-administered IMI. In addition to the data on IMI, a parent chemical, photochemical and pharmacokinetic profiling of its metabolite, DMI, led to reliable phototoxicity prediction of orally-administered IMI. Thus, characterization of the photosafety of metabolites would generate reliable information on the phototoxicity risk of parent chemicals, and the proposed strategy may facilitate comprehensive photosafety assessment of drug candidates in pharmaceutical development.

Introduction: Oleuropein is a promising nutraceutical found in abundance in olive leaf, with reported antioxidant and anti-inflammatory properties, and hence could be a valuable treatment for dermatological diseases such as psoriasis.Areas covered: In order to overcome the poor skin penetration of oleuropein, it was formulated in a microemulsion nanocarrier. The selected microemulsion formulation displayed a particle size of 30.25 ± 4.8 nm, zeta potential 0.15 ± 0.08 mV and polydispersity index 0.3 ± 0.08, with storage stability for 1 year in room temperature and total deposition in skin layers amounting to 95.67%. Upon clinical examination in psoriatic patients, the oleuropein microemulsion formulation was proven superior to the marketed Dermovate cream composed of clobetasol propionate, in terms of reduction of Psoriasis Area and Severity Index (PASI) scores, as well dermoscopic imaging and morphometric analysis of the psoriasis lesions, in which oleuropein microemulsion exhibited marked improvement in the clinical manifestations of psoriasis.Expert opinion: The findings of this study further prove the promising role of nutraceuticals, as well as nanoparticles in enhancing the therapeutic outcome of treatments, and open new era of applications in a variety of diseases.