A novel anti-pruritic: Topical co-administration of high molecular weight hyaluronan (HMWH) with protamine, a transdermal transport enhancer.

Pruritis, the sensation of itch, is produced by multiple substances, exogenous and endogenous, that sensitizes specialized sensory neurons (pruriceptors and pruri-nociceptors). Unfortunately, many patients with acute and chronic pruritis obtain only partial relief when treated with currently available treatment modalities. We recently demonstrated that the topical application of high molecular weight hyaluronan (HMWH), when combined with vehicles containing transdermal transport enhancers, produce potent long-lasting reversal of nociceptor sensitization associated with inflammatory and neuropathic pain. In the present experiments we tested the hypothesis that the topical formulation of HMWH with protamine, a transdermal transport enhancer, can also attenuate pruritis. We report that this topical formulation of HMWH markedly attenuates scratching behavior at the nape of the neck induced by serotonin (5-hydroxytryptamine, 5-HT), in male and female rats. Our results support the hypothesis that topical HMWH in a transdermal transport enhancer vehicle is a strong anti-pruritic.

Topical Prescription Management.

With recent advances in topical therapies for atopic dermatitis (AD), steroid-sparing options like calcineurin inhibitors, Janus kinase (JAK) inhibitors, and phosphodiesterase-4 (PDE-4) inhibitors are becoming mainstays in therapy, underscoring the importance of careful selection and usage of topical corticosteroids (TCSs) to minimize side effects. Alongside the necessity of emollient use, these steroid-sparing alternatives offer rapid itch relief and efficacy in improving disease severity. While TCSs still hold a prominent role in AD management, promising novel topical treatments like tapinarof and live biotherapeutics to modulate the skin microbiome are also discussed. Overall, the recent addition of novel topical therapies offers diverse options for AD management and underscores the importance of topical treatments in the management of AD.

Rapid and sustained improvements in itch and quality of life with upadacitinib plus topical corticosteroids in adults and adolescents with atopic dermatitis: 52-week outcomes from the phase 3 AD Up study.

Purpose: Atopic dermatitis (AD) adversely impacts quality of life (QoL). We evaluated the effect of upadacitinib, an oral selective Janus kinase inhibitor approved for moderate-to-severe AD, plus topical corticosteroids (+TCS) on patient-reported outcomes (PROs) over 52 weeks.Materials and methods: In the phase 3 AD Up study (NCT03568318), adults and adolescents with moderate-to-severe AD were randomized 1:1:1 to once-daily upadacitinib 15 mg, 30 mg, or placebo + TCS. Itch, skin pain/symptoms, sleep, QoL, daily activities, emotional state, mental health, and patient impressions of disease severity/improvement/treatment satisfaction were assessed.Results: This analysis included 901 patients. Within 1-2 weeks, PRO improvements were greater with both upadacitinib doses than with placebo (p <.05). Improvements increased through weeks 4-8; rates were generally maintained through week 52. At week 52, the proportion of patients with clinically meaningful improvements in itch (Worst Pruritus Numerical Rating Scale improvement ≥4), skin pain (AD Symptom Scale Skin Pain improvement ≥4), sleep (AD Impact Scale [ADerm-IS] Sleep improvement ≥12), daily activities (ADerm-IS Daily Activities improvement ≥14), and emotional state (ADerm-IS Emotional State improvement ≥11) ranged from 62.1%-77.7% with upadacitinib 15 mg + TCS and 71.3%-83.6% with upadacitinib 30 mg + TCS.Conclusions: Upadacitinib + TCS results in rapid, sustained improvements in burdensome AD symptoms and QoL.

Propellant Free Pressurized Spray System of Etodolac to Manage Acute Pain Conditions: In Vitro and In Vivo Evaluation.

This study aimed to develop a propellant-free topical spray formulation of Etodolac (BCS-II), a potent NSAID, which could be beneficial in the medical field for the effective treatment of pain and inflammation conditions. The developed novel propellant-free spray formulation is user-friendly, cost-effective, propellant-free, eco-friendly, enhances the penetration of Etodolac through the skin, and has a quick onset of action. Various formulations were developed by adjusting the concentrations of different components, including lecithin, buffering agents, film-forming agents, plasticizers, and permeation enhancers. The prepared propellant-free spray formulations were then extensively characterized and evaluated through various in vitro, ex vivo, and in vivo parameters. The optimized formulation exhibits an average shot weight of 0.24 ± 0.30 ml and an average drug content or content uniformity of 87.3 ± 1.01% per spray. Additionally, the optimized formulation exhibits an evaporation time of 3 ± 0.24 min. The skin permeation study demonstrated that the permeability coefficients of the optimized spray formulation were 21.42 cm/h for rat skin, 13.64 cm/h for mice skin, and 18.97 cm/h for the Strat-M membrane. When assessing its potential for drug deposition using rat skin, mice skin, and the Strat-M membrane, the enhancement ratios for the optimized formulation were 1.88, 2.46, and 1.92, respectively against pure drug solution. The findings from our study suggest that the propellant-free Etodolac spray is a reliable and safe topical formulation. It demonstrates enhanced skin deposition, and improved effectiveness, and is free from any skin irritation concerns.

Topical Tacrolimus Ointment Alone versus in Combination with Microneedling for Refractory Stable Vitiligo.

OBJECTIVE: To assess the efficacy of microneedling in combination with topical tacrolimus ointment 0.1% versus topical tacrolimus ointment 0.1% for treatment of refractory stable vitiligo. STUDY DESIGN: Comparative cross-sectional study. Place and Duration of the Study: Department of Dermatology, PNS Shifa, Karachi, Pakistan, from December 2022 to May 2023. METHODOLOGY: The study included 30 clinically diagnosed individuals of either gender who had refractory symptoms and aged between 20 and 60 years. For every patient, two comparable lesions on two comparable limb regions were selected. Group A (right side) received treatment with both topical tacrolimus ointment 0.1% twice daily in addition to microneedling every two weeks, whereas, Group B (left side) was treated with topical tacrolimus ointment 0.1% only. Every lesion was investigated as a separate entity. Both groups were subsequently observed for a further six months. RESULTS: When topical tacrolimus ointment 0.1% was combined with microneedling, the total re-pigmentation rate was substantially higher than the usage of tacrolimus ointment 0.1% alone. Fifty-three percent of lesions treated with topical tacrolimus ointment 0.1% alone and 76.7% of lesions treated with microneedling in conjunction with it showed a good-to-excellent response. No adverse negative effects were noted. During the follow-up period, no problems or recurrences were noted. CONCLUSION: Tacrolimus ointment combined with microneedling is a successful treatment for refractory stable vitiligo. KEY WORDS: Dermapen, Depigmentation, Microneedling, Tacrolimus ointment, Vitiligo.

Photodynamic Skincare: A Prospective Single-Center Study.

BACKGROUND: Peer-reviewed, clinical studies measuring the efficacy and usability of skin care products enhance their integrity and may guide experts in the field in providing recommendations. A single-blind, prospective clinical study was designed to assess the subject satisfaction, clinical benefit, and safety of three photodynamic topical formulations referred to as MMSRepose (MMSRep), MMSRevive (MMSRev), and MMSBalance (MMSB).  Methods: Thirteen male and female patients (mean age 49 +/- 17.8 years) applied one of the three topical serums twice daily over a period of 12 weeks. Subjects returned for photography, and blinded investigator evaluation of rhytides (fine lines) and dyspigmentation were measured on a 6- and 4-point scale, respectively. Patient-perceived efficacy of multiple clinical outcomes was measured on a 5-point scale.  Results: 100% of subjects reported at least a 1-grade improvement in global aesthetic at the conclusion of the study. Investigator assessment revealed an overall 53.3% decrease in rhytides, correlating to a mean point reduction from 1.65 +/- 0.77 to 0.77 +/- 0.53 (P<0.001) from baseline to week 12. Investigator assessment of dyspigmentation revealed a 62.7% decrease, correlating to a mean point reduction of 1.85 +/- 0.68 from week 1 to 0.69 +/- 0.48 at week 12 (P<0.001). CONCLUSION: Photodynamic serums demonstrate clinical efficacy in skin rejuvenation and high user satisfaction. There were no serious adverse events. This study is limited by the inability to randomize to placebo due to the small sample size, as subject retention was heavily impacted by the SARS-CoV-2 pandemic. Future studies may be indicated to undergo comparison with a larger cohort.  J Drugs Dermatol. 2024;23(5):332-337. doi:10.36849/JDD.7167.

Patient- and Clinician-Reported Outcomes for Tirbanibulin in Actinic Keratosis in Clinical Practice Across the United States (PROAK).

BACKGROUND: The Patient-Reported Outcomes in Actinic Keratosis (PROAK) study evaluated patient- and clinician-reported outcomes (PRO; ClinRO) during 24 weeks of follow-up among adult patients with actinic keratosis (AK) on the face or scalp who were administered tirbanibulin 1% ointment in real-world community practices in the United States.  Methods: Quality of life (QoL) was assessed by Skindex-16 at week (W) 8. Additionally, effectiveness (Investigator Global Assessment [IGA]), PRO and ClinRO (Treatment Satisfaction Questionnaire for Medication and Expert Panel Questionnaire), safety, and tolerability were assessed at W8 and W24. RESULTS: The safety population included 300 patients; the full analysis set included 290 patients (278 patients at W24). At W8, a statistically significant difference (P<0.03) was observed for Skindex-16 domains in all assessed subgroups. Clinicians and patients reported high global satisfaction (mean [SD] scores of 74.9 [23.9] and 72.0 [24.6], respectively) at W24. Overall skin appearance improved from baseline to W24 (83.6% clinicians; 78.5% patients). IGA success (IGA score of 0-1) was achieved by 71.9% of patients at W24 with a similar % at W8 (73.8%) suggesting a stable effectiveness over time. About 5% of patients reported at least one adverse event, 4% reported at least one serious adverse event and no patients reported serious adverse drug reactions. At W8, the most frequently reported local skin reactions were mild/moderate erythema (47.6%) and flaking/scaling (49.6%). CONCLUSIONS: Treatment with tirbanibulin demonstrated effectiveness in the management of AK lesions and a favorable safety and tolerability profile. Furthermore, QoL was improved as early as W8, and both patients and clinicians reported high levels of treatment satisfaction, independently of patients' characteristics. J Drugs Dermatol. 2024;23(5):338-346. doi:10.36849/JDD.8264.

Ruxolitinib 1.5% Topical Cream for the Treatment of Pediatric Alopecia Areata.

Alopecia areata (AA) is a common autoimmune disorder. Although its pathogenesis is not fully understood, AA involves CD8 T cell-mediated destruction of the hair follicle. Several treatment options exist; however, there is minimal evidence in the pediatric population. Currently, there are no curative treatments for AA. The literature suggests that Janus kinase (JAK) inhibitors may be an effective treat-ment for AA, but evidence in pediatric patients is limited. Here, we report a case of severe pediatric AA treated with topical ruxolitinib, a JAK inhibitor. J Drugs Dermatol. 2024;23(5):378-379. doi:10.36849/JDD.7782.

An Over-the-Counter Healing Ointment: Benefits in Dry Skin and Wound Healing.

BACKGROUND: The use of ointments can be beneficial for dry, chapped, or cracked skin and also for supporting wound healing. We describe the results of 2 studies with an over-the-counter healing ointment (HO) to evaluate the effects on skin hydration and in the setting of wound healing after dermatologic procedures.  Methods: Study 1 was a single-center, in-use study using HO on qualified areas at least once daily for 4 weeks in subjects with dry, cracked body skin and self-perceived sensitive skin. Study 2 was a multi-center study of wound healing in subjects using HO on a daily basis after having dermatologic surgical procedures.  Results: In Study 1, there was a significant reduction in skin dryness after 1 and 4 weeks of HO use (P<0.05). Image analysis of the skin revealed a significant increase in skin smoothness after the first application of HO in 100% of subjects (P<0.05). Tolerability and safety were excellent, and HO was well-perceived by subjects throughout the study. In Study 2, HO improved clinical assessments at all time points compared with baseline with a decrease in erythema, edema, scabbing/crusting, and an improvement in overall wound appearance (P<0.05). There was no worsening or significant increase in measures for tolerability parameters at any study visits. Additionally, HO achieved a favorable perception by study subjects.  Conclusions: HO has a well-established safety profile and has been shown to improve both skin hydration and the overall wound healing process after dermatologic surgical procedures. J Drugs Dermatol. 2024;23(5):360-365. doi:10.36849/JDD.8224.

Transdermal Delivery of Niacin Through Polysaccharide Films Ameliorates Cutaneous Flushing in Experimental Wistar Rats.

BACKGROUND: Niacin, an established therapeutic for dyslipidemia, is hindered by its propensity to induce significant cutaneous flushing when administered orally in its unmodified state, thereby constraining its clinical utility. OBJECTIVE: This study aimed to fabricate, characterize, and assess the in-vitro and in-vivo effectiveness of niacin-loaded polymeric films (NLPFs) comprised of carboxymethyl tamarind seed polysaccharide. The primary objective was to mitigate the flushing-related side effects associated with oral niacin administration. METHODS: NLPFs were synthesized using the solvent casting method and subsequently subjected to characterization, including assessments of tensile strength, moisture uptake, thickness, and folding endurance. Surface characteristics were analyzed using a surface profiler and scanning electron microscopy (SEM). Potential interactions between niacin and the polysaccharide core were investigated through X-ray diffraction experiments (XRD) and Fourier transform infrared spectroscopy (FTIR). The viscoelastic properties of the films were explored using a Rheometer. In-vitro assessments included drug release studies, swelling behavior assays, and antioxidant assays. In-vivo efficacy was evaluated through skin permeation assays, skin irritation assays, and histopathological analyses. RESULTS: NLPFs exhibited a smooth texture with favorable tensile strength and moisture absorption capabilities. Niacin demonstrated interaction with the polysaccharide core, rendering the films amorphous. The films displayed slow and sustained drug release, exceptional antioxidant properties, optimal swelling behavior, and viscoelastic characteristics. Furthermore, the films exhibited biocompatibility and non-toxicity towards skin cells. CONCLUSION: NLPFs emerged as promising carrier systems for the therapeutic transdermal delivery of niacin, effectively mitigating its flushing-associated adverse effects.

The role of vitamins and nutrients in rosacea.

Rosacea is a common inflammatory skin condition displaying symptoms like flushing, erythema, papules, and pustules. Oral antibiotics, despite long-term adverse effects, are often used due to topical treatment limitations, underscoring the need for cost-effective choices like dietary modifications. Our review investigates the role of vitamins and minerals in rosacea, and provides evidence-based recommendations for supplementation and topical treatment of these nutrients for rosacea. An online search was performed on PubMed, Web of Science, Science Direct, Google Scholar, and ClinicalTrials.gov from 1998 to 2023. Included studies were summarized and assessed for quality and relevance in rosacea management. Varied outcomes emerged concerning the impact of essential vitamins and minerals on rosacea treatment. Vitamin A derivatives, specifically oral isotretinoin, demonstrated significant efficacy, with a 90% reduction in lesions, complete remission in 24% of patients, and marked improvement in 57% of patients. Vitamin B3 derivatives, such as topical 1-methylnicotinamide 0.25% and NADH 1%, improved symptoms in 76.4% (26/34) and 80% of patients, respectively. Outcomes for vitamin D, vitamin C, and zinc supplementation varied across studies. However, zinc sulfate solution 5% significantly reduced acne rosacea severity for patients with 40% and 60% exhibiting a moderate or good response, respectively. Omega-3 fatty acids showed significant improvement in alleviating xerophthalmia in 64% of patients with ocular rosacea. Vitamins and minerals hold potential in managing rosacea symptoms, offering a safe and cost-effective alternative or adjunctive treatment option. Currently, there are no established recommendations regarding their supplementation for rosacea. Studies assessing serum levels of vitamins and minerals in relation to rosacea are warranted, as this avenue holds potential for future advancements in the field.

[Development of Transdermal Formulation Based on Nanotechnology and Elucidation of Its Drug Delivery Pathways].

Transdermal drug delivery is a formulation in which the drug is absorbed through the skin for systemic action. Its advantages include avoidance of first-pass effects, sustained drug supply, and ease of administration and discontinuation. Drugs administered transdermally transfer into the blood circulation through the stratum corneum, epidermis, and dermis. The stratum corneum on the skin surface plays a barrier function in skin absorption. Therefore, developing of transdermal drug delivery systems requires innovations that overcome the barrier function of the stratum corneum and improve skin permeation. This review examines the usefulness of transdermal formulations based on solid nanoparticles using raloxifene. Milled raloxifene was gelled with (mRal-NPs) or without menthol (Ral-NPs) using Carbopol. The drug release and transdermal penetration were measured using a Franz diffusion cell, and the therapeutic evaluation of osteoporosis was determined in an ovariectomized rat model. Although the raloxifene released from Ral-NPs remained in the nanoparticle state, the skin penetration of raloxifene nanoparticles was prevented by the stratum corneum in rat. The inclusion of menthol in the formulation attenuated the barrier function of the stratum corneum and permitted raloxifene nanoparticles to penetrate through the skin. Moreover, macropinocytosis relates to the formulation's skin penetration, including menthol (mRal-NPs). Applying mRal-NPs attenuated the decreases in calcium level and stiffness of bones of ovariectomized rats. This information can support future studies aimed at designing novel transdermal formulations.

Nanosuspension-Loaded Dissolving Microneedle Patches for Enhanced Transdermal Delivery of a Highly Lipophilic Cannabidiol.

Purpose: Transdermal Drug Delivery System (TDDS) offers a promising alternative for delivering poorly soluble drugs, challenged by the stratum corneum's barrier effect, which restricts the pool of drug candidates suitable for TDDS. This study aims to establish a delivery platform specifically for highly lipophilic drugs requiring high doses (log P > 5, dose > 10 mg/kg/d), to improve their intradermal delivery and enhance solubility. Methods: Cannabidiol (CBD, log P = 5.91) served as the model drug. A CBD nanosuspension (CBD-NS) was prepared using a bottom-up method. The particle size, polydispersity index (PDI), zeta potential, and concentration of the CBD-NS were characterized. Subsequently, CBD-NS was incorporated into dissolving microneedles (DMNs) through a one-step manufacturing process. The intradermal dissolution abilities, physicochemical properties, mechanical strength, insertion depth, and release behavior of the DMNs were evaluated. Sprague-Dawley (SD) rats were utilized to assess the efficacy of the DMN patch in treating knee synovitis and to analyze its skin permeation kinetics and pharmacokinetic performance. Results: The CBD-NS, stabilized with Tween 80, exhibited a particle size of 166.83 ± 3.33 nm, a PDI of 0.21 ± 0.07, and a concentration of 46.11 ± 0.52 mg/mL. The DMN loaded with CBD-NS demonstrated favorable intradermal dissolution and mechanical properties. It effectively increased the delivery of CBD into the skin, extended the action's duration in vivo, and enhanced bioavailability. CBD-NS DMN exhibited superior therapeutic efficacy and safety in a rat model of knee synovitis, significantly inhibiting TNF-α and IL-1ß compared with the methotrexate subcutaneous injection method. Conclusion: NS technology effectively enhances the solubility of the poorly soluble drug CBD, while DMN facilitates penetration, extends the duration of action in vivo, and improves bioavailability. Furthermore, CBD has shown promising therapeutic outcomes in treating knee synovitis. This innovative drug delivery system is expected to offer a more efficient solution for the administration of highly lipophilic drugs akin to CBD, thereby facilitating high-dose administration.

Formulation and evaluation of miconazole lipogel for enhanced drug permeation.

Hydrophilic drugs could be incorporated into the skin surface by manes of Lipogel. This study aimed to prepare miconazole lipogel with natural ingredients to enhance drug permeability using dimethyl Sulfoxide (DMSO). The miconazole lipogels, A1 (without DMSO) and A2 (with DMSO) were formulated and evaluated for organoleptic evaluation, pH, viscosity, stability studies, freeze-thawing, drug release profile and drug permeation enhancement. Results had stated that prepared lipogel's pH falls within the acceptable range required for topical delivery (4 to 6) while both formulations show good results in organoleptic evaluation. The A2 formulation containing DMSO shows better permeation of miconazole (84.76%) on the artificial skin membrane as compared to A1 lipogel formulation (50.64%). In in-vitro drug release studies, A2 for-mulation showed 87.48% drug release while A1 showed just 60.1% drug release from lipogel. Stability studies were performed on model formulations under environmental conditions and both showed good spreadibility, stable pH, free of grittiness and good consistency in formulation. The results concluded that A2 formulation containing DMSO shows better results as compared to DMSO-free drug lipogel.

Rapid Correction of the Hypoglycemia State in Nonhuman Primates Using a Glucagon Long-Dissolving Microneedle Patch.

The timely administration of glucagon is a standard clinical practice for the treatment of severe hypoglycemia. However, the process involves cumbersome steps, including the reconstitution of labile glucagon and filling of the syringe, which cause considerable delays in emergency situations. Moreover, multiple dosages are often required to prevent the recurrence of the hypoglycemic episode because of the short half-life of glucagon in plasma. Herein, we develop a glucagon-loaded long-dissolving microneedle (GLMN) patch that exhibits the properties of fast onset and sustained activity for the effective treatment of severe hypoglycemia. Three types of MN patches were fabricated with different dimensions (long, medium, and short). The longer MN patch packaged a higher dosage of glucagon and exhibited supreme mechanical strength compared to the shorter one. Additionally, the longer MN patch could insert more deeply into the skin, resulting in higher permeability of glucagon across the skin tissue and more rapid systemic absorption as compared with the shorter MN patch. The GLMN patch was observed to reverse the effects of hypoglycemia within 15 min of application in animal models (specifically, rat and rhesus monkey models) and maintained long-term glycemic control, owing to highly efficient drug permeation and the drug reservoir effect of the MN base. The current study presents a promising strategy for the rapid reversal of severe hypoglycemia that exhibits the desirable properties of easy use, high efficiency, and sustained action.

Nanodiamond-based berberine aquasomes for enhancing penetration across epidermis to treat psoriasis.

The use of berberine hydrochloride (BCS class III) has limited application in psoriasis, when given as topical drug delivery systems, due to low permeability in the skin layer. Hence, berberine hydrochloride-loaded aquasome nanocarriers were developed for skin targeting, particularly epidermis (primary site of psoriasis pathophysiology) and enhance the skin permeability of berberine hydrochloride. Aquasomes were formulated using the adsorption method and characterized by structural morphology TEM, % drug adsorption, drug release profile (in-vitro and ex-vivo), in-vivo efficacy study and stability study. The reduced particle size and higher surface charge of SKF3 formulation (263.57 ± 27.78 nm and -21.0 ± 0.43 mV) showed improved stability of aquasomes because of the development of higher surface resistance to formation of aggregates. The adsorption of hydrophilic berberine and the non-lipidic nature of aquasomes resulted in % adsorption efficiency (%AE) of 94.46 ± 0.39 %. The controlled first-order release behavior of aquasomes was reported to be 52.647 ± 14.63 and 32.08 ± 12.78 % in in-vitro and ex-vivo studies, respectively. In-vivo studies demonstrated that topical application of berberine hydrochloride loaded aquasomes significantly alleviated psoriasis symptoms like hyperkeratosis, scaling and inflammation, due to the reduction in the inflammatory cytokines (IL-17 and IL-23). Therefore, aquasome formulation exhibits an innovative approach for targeted application of berberine hydrochloride in the management of psoriasis.

[Rapamycin and HPPH Co-Loaded Nanodrug Delivered via Dissolvable Microneedles to Treat Port-Wine Stains]. / å ±è½½é›·å¸•éœ‰ç´ å’Œå ‰å ‹æ´›çš„çº³ç±³è¯ç‰©å¤åˆå¯æº¶è§£å¾®é’ˆæ²»ç–—é²œçº¢æ–‘ç—£çš„å®žéªŒç ”ç©¶.

Objective: Port-wine stains are a kind of dermatological disease of congenital capillary malformation. Based on the biological characteristics of port-wine stains and the advantages of microneedle transdermal administration, we intend to construct a nanodrug co-loaded with rapamycin (RPM), an anti-angiogenesis drug, and photochlor (HPPH), a photosensitizer, and integrate the nanodrug with dissolvable microneedles (MN) to achieve anti-angiogenesis and photodynamic combination therapy for port-wine stains. Methods: First, RPM and HPPH co-loaded nanoparticles (RPM-HPPH NP) were prepared by the emulsification solvent-volatilization method, and its ability to generate reactive oxygen species (ROS) was investigated under 660 nm laser irradiation. Mouse hemangioendothelioma endothelial cells (EOMA) were used as the subjects of the study. The cellular uptake behaviors were examined by fluorescence microscopy and flow cytometry. The cytotoxicity effects of RPM-HPPH NP with or without 660 nm laser irradiation on EOMA cells were examined by MTT assays (with free RPM serving as the control). Then, hyaluronic acid (HA) dissolvable microneedles loaded with RPM-HPPH NP (RPM-HPPH NP@HA MN) were obtained by compounding the nanodrug with HA dissolvable microneedle system through the molding method. The morphological characteristics and mechanical properties of RPM-HPPH NP@HA MN were investigated by scanning electron microscope and electronic universal testing machine. The penetration ability of RPM-HPPH NP@HA MN on the skin of nude mice was evaluated by trypan blue staining and H&E staining experiment. Results: The RPM-HPPH NP prepared in the study had a particle size of 150 nm and generated large amounts of ROS under laser irradiation. At the cellular level, RPM-HPPH NP was taken up by EOMA cells in a time-dependent manner. The cytotoxicity of RPM-HPPH NP was higher than that of free RPM with or without laser irradiation. Under laser irradiation, RPM-HPPH NP exhibited stronger cytotoxic effects and the difference was statistically significant (P<0.05). The height of the needle tip of RPM-HPPH NP@HA MN was 600 µm and the mechanical property of a single needle was 0.75048 N. Trypan blue staining and HE staining showed that pressing on the microneedles could produce pores on the skin surface and penetration of the stratum corneum. Conclusion: RPM-HPPH NP@HA MN can deliver RPM-HPPH NP percutaneously to the lesion tissue and realize the synergistic treatment of port-wine stains with anti-angiogenic therapy and photodynamic therapy, providing a new strategy for the construction of nanodrug-loaded microneedle delivery system and the clinical treatment of port-wine stains.

Eugenol-Loaded Transethosomal Gel for Improved Skin Delivery and Treatment of Atopic Dermatitis.

Atopic dermatitis is a skin condition characterized by lichenification (thickening and increased skin marking), eczematous lesions, dry skin, itching, and pruritus. Eugenol is an aromatic polyphenolic compound that has attracted the attention of researchers due to its anti-inflammatory, anti-oxidant, and anti-cancer properties. The primary goal of the present study was to develop and evaluate eugenol-loaded transethosomes for the treatment of AD. Eugenol-loaded transethosomes were formulated using the ethanol injection method and subsequently subjected to particle size analysis, zeta potential, entrapment efficiency, deformability index, and HRTEM analysis. Transethosomal gel was prepared by direct-dispersion method by using Carbopol 940®. Results showed transethosomes to be lipid bilayer structures with acceptable size, and high entrapment efficiency. Transethosomal formulation showed shear-thinning behavior. Eugenol-loaded transethosomal gel was significantly able to enhance the retention of the drug in the skin. Transethosomal gel was significantly able to reduce Ear thickness, DLC, TLC, and IL-6 levels in mice model of AD. These results indicate that the eugenol-loaded transethosomal gel could be a promising carrier for the topical administration of eugenol for the treatment of AD.

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.