Microneedle Transdermal Delivery of Compound Betamethasone in Alopecia Areata - A Randomized Controlled Trial.

BACKGROUND: Alopecia areata (AA) places a considerable burden on patients. While intralesional glucocorticoid injection is an important therapy, it can cause severe pain. OBJECTIVE: To compare the efficacy and pain levels of microneedle transdermal delivery of compound betamethasone versus traditional intralesional injection in mild-to-moderate AA. METHODS: We conducted a randomized controlled trial in AA patients with a SALT score < 50. Both groups received monthly compound betamethasone injections: Group A via intralesional injections, and Group B via transdermal microneedle delivery. The primary outcome was the reduction in SALT score after three months. RESULTS: With 80 patients enrolled, baseline SALT scores were similar between group A (9.250±5.300) and group B (10.65±9.445). After 3 months, the mean SALT reduction was 7.000±4.5017 in group A and 8.075±8.014 in group B, with no statistical difference. Remission rates for SALT30/50/75/90 were 92.50/90.00/57.50/42.50% in group A and 95.00/87.50/72.50/40% in group B, with no significant difference. Group B had a significantly lower Visual Analog Scale (VAS) pain score than group A (4.000±1.174 vs. 5.281±2.098, p=0.0047). LIMITATIONS: The study focused on mild-to-moderate patchy AA, limiting insights into severe cases. CONCLUSION: Microneedle transdermal delivery of compound betamethasone in mild-to-moderate patchy AA demonstrates efficacy comparable to traditional intralesional injection, with reduced pain.

Luteolin-loaded Invasomes Gel for Transdermal Delivery: Development, Optimization, in-vitro, and Preclinical Evaluation.

Luteolin (LN), is an herbal bioactive flavone and exhibits many pharmacological activities. However, the bioavailability of LN is limited due to its inadequate solubility and significant first-pass metabolism. The present study developed transdermal LN-loaded invasomes (IVM) gel to improve the therapeutic efficacy. The LN-IVM was prepared and optimized by 2 3 factorial designs. LN-IVM was characterized for physicochemical parameters. The optimized LN-IVM (LN-IVMopt) was incorporated into HPMC-K4M gel and evaluated for viscosity, spreadability, and irritation. Further LN-IVM gel was evaluated for drug release, ex-vivo permeation, pharmacokinetic and pharmacodynamics study. LN-IVMopt showed 300.8±2.67 nm of VS, 0.258 of PDI, 89.92±1.29% of EE, and a zeta potential of -18.2 mV. LN-IVM exhibited spherical morphology. FTIR and XRD results demonstrated that LN was encapsulated into IVM matrix. The optimized IVM gel (LN-IVMoptG2) exhibited excellent viscosity, spreadability, and sustained release of LN (91.32±2.95% in 24 h). LN-IVMoptG2 exhibited statistically significant (p < 0.05) higher flux (5.79 µg/h/cm2 ) than LN-gel (2.09 µg/h/cm2 ). The apparent permeability coefficient of plain LN gel and LN- IVMoptG was 1.15×10-5 cm/min and 3.22×10-5 cm/min respectively. LN-IVMoptG2 showed no irritation (score 0.0) throughout the study (60 min). The relative bioavailability of LN from LN-IVMopt-G2 (transdermal) was 2.38±0.19 fold as compared to LN-Sus (oral) and 1.81±0.15-fold than plain LN-gel (transdermal). The LN-IVMoptG2 showed a substantial lessening in the paw volume up to 12 h (17.48±1.94% swelling) than plain LN-gel (44.77±2.82% swelling). The finding concluded that the IVM gel is a novel, effective, and safe approach for the delivery of LN transdermally to improve its therapeutic efficacy.

A wearable iontophoresis enables dual-responsive transdermal delivery for atopic dermatitis treatment.

Atopic dermatitis is a chronic, inflammation skin disease that remains a major public health challenge. The current drug-loading hydrogel dressings offer numerous benefits with enhanced loading capacity and a moist-rich environment. However, their development is still limited by the accessibility of a suitable driven source outside the clinical environment for precise control over transdermal delivery kinetics. Here, we prepare a sulfonated poly(3,4-ethylenedioxythiophene) (PEDOT) polyelectrolyte hydrogel drug reservoir that responds to different stimuli-both endogenous cue (body temperature) and exogenous cue (electrical stimulation), for wearable on-demand transdermal delivery with enhanced efficacy. Functioned as both the drug reservoir and cathode in a Zn battery-powered iontophoresis patch, this dual-responsive hydrogel achieves high drug release efficiency (68.4 %) at 37 °C. Evaluation in hairless mouse skin demonstrates the efficacy of this technology by facilitating transdermal transport of 12.2 µg cm-2 dexamethasone phosphate when discharged with a 103 Ω external resistor for 3 h. The Zn battery-driven iontophoresis results in an effective treatment of atopic dermatitis, displaying reductions in epidermal thickness, mast cell infiltration inhibition, and a decrease in IgE levels. This work provides a new treatment modality for chronic epidermal diseases that require precise drug delivery in a non-invasive way.

In vitro assessment of skin permeation properties of enzymatically derived oil-based fatty acid esters of vitamin C.

Current topical formulations containing vitamin C face limitations in therapeutic effectiveness due to the skin's selective properties that impede drug deposition. Consequently, the widespread use of toxic and irritating chemical permeation enhancers is common. Hereby, we investigated enzymatically derived fatty acid ascorbyl esters (FAAEs) obtained using natural oils for their skin permeation properties using the Strat-M® skin model in a Franz cell diffusion study. By evaluating various cosmetic formulations without added enhancers, we found that emulgel is most suitable for enhancing the cutaneous and transdermal delivery of FAAEs. Furthermore, medium-chain coconut oil-derived FAAEs exhibited faster diffusion rates compared to sunflower oil-based FAAEs with long-side acyl residues, including the commonly applied ascorbyl palmitate. Experimental data were successfully fitted using the Peppas and Sahlin model, which accounted for a lag phase and the combined effect of Fickian diffusion and polymer relaxation. In the case of long-chain esters, the lag phase was prolonged, and the calculated effective diffusion coefficients (Deff) were lower compared to medium-chain FAAEs. Accordingly, the highest Deff value was observed for ascorbyl caprylate, being even 60 times higher than for ascorbyl palmitate. These results suggest the emerging potential of emulgel with incorporated coconut oil-derived FAAEs for efficiently delivering vitamin C into the skin.

Vat-based photopolymerization 3D printing: From materials to topical and transdermal applications.

Three-dimensional (3D) printing is an innovative manufacturing method with the potential to revolutionize topical and transdermal dosage forms. Nowadays, it is established that Vat-based photopolymerization (VP) 3D printing technologies offer superior printing efficiency and versatility compared to other 3D printing technologies available on the market. However, there are some limitations that impair their full application in pharmaceutical contexts, such as the lack of a range of biocompatible materials for topical and transdermal applications. This review article explores all types of VP-based 3D printing and discusses the relevance of implementing this kind of technology. We start with a detailed description of the printing process, focusing on the commercial materials available and lab-made resins proposed by different authors. We also review recent studies in this field, which mainly focus on the fabrication of transdermal devices based on microneedle arrays. In the future, it is expected that the manufacturers of 3D printers invest in modifications to the printing apparatus to allow the simultaneous printing of different resins and/or compound types, which will open frontiers to the personalization of treatment approaches.

Microneedles as a potential platform for improving antibiotic delivery to bacterial infections.

Bacterial infections are mainly managed by the administration of antibiotics, which are either cytotoxic or cytostatic to microbes. In some cases, it is inconvenient to treat infections caused by bacteria using the traditional oral route for antibiotic administration. This can be due to the limited oral bioavailability of antibiotics, their gastrointestinal tract (GIT) adverse effects, and the increased possibility of the appearance of resistant strains. In addition, the fact that many populations are needle-phobic restricts the switch from the oral to the parenteral route. Furthermore, poor drug permeation throughout the stratum corneum of topically applied antibiotics causes low systemic bioavailability. Therefore, microneedles (MNs) have emerged as viable medicinal devices for the delivery of antibiotics, either for local or systemic effects. MNs represent a minimally invasive, painless way of administration that can be self-administered by the patient without the need of medical professionals. This review has specifically focused on MNs as a promising approach for the delivery of antibiotics; it has discussed the different types of MNs, their advantages, and possible limitations for the delivery of antibiotics. Recent studies on the incorporation of antibiotics into various types of MNs, either for topical or transdermal delivery are highlighted, and finally, we present the conclusion and future perspectives.

Ionic liquid combined with cationic liposome co-delivers microphthalmia-associated transcription factor small interfering RNA to regulate melanogenesis.

Suppressing allele-specific genes using small interfering RNAs (siRNAs) can effectively whiten skin by influencing cellular gene and protein expression. Topical delivery of siRNA is a promising alternative to injections for RNA interference. However, the barrier function of the skin hinders the effective penetration of siRNA. Here, we report, a novel approach to achieve the transdermal delivery of effective siRNA doses using a complementary synergistic strategy of an ionic liquid (IL) and cationic liposome (CL). Microphthalmia-associated transcription factor (MITF) siRNA molecules were formed through electrostatic adsorption of the IL and CL to form positively charged nanocomposites, which were named IL-CL/p-siM. IL-CL/p-siM has a particle size of 171.47 nm, ζ-potential of 29.94 mV, high encapsulation rate of 92.11 %, and pH-sensitive release properties. In vitro studies on porcine skin confirmed the additive/synergistic effect of this strategy in enhancing epidermal and dermal penetration. This combination enabled superior transfection efficiency and cell viability while inhibiting melanin synthesis in skin melanocytes by downregulating the expression of genes downstream of MITF, namely tyrosinase-related protein-1, tyrosinase, and tyrosinase-related protein-2, which are associated with the melanocortin 1 receptor. We also conducted clinical studies that demonstrated its potential in treating melasma and its anti-melanotic efficacy. To summarize, IL-CL/p-siM represents a simple, personalized, and scalable platform for effective local delivery of siRNA to treat skin complications.

Enhanced stability and reduced irritation of 4-n-butylresorcinol via nanoemulsion formulation: Implications for skin pigmentation treatment.

4-n-butylresorcinol (4-nBR) is a valuable ingredient to lighten skin and reduce pigmentation, contributing to an even skin tone and a more youthful appearance. However, its poor solubility, low stability, and strong irritation to the skin limit its application. In this study, 4-nBR was prepared into 4-n-butylresorcinol nanoemulsion (4-nBR-NE) for the first time, enhancing the solubility and stability of 4-nBR while greatly reducing its skin irritation. The relationship between the viscosity of nanoemulsion and the formulation process, as well as the impact of surfactant ratio on the formability of 4-nBR-NE were further studied. This led to the successful development of a nanoemulsion with adjustable viscosity (AV-NE) and with a low surfactant content. The particle size of 4-nBR-NE was 13.34 ± 0.16 nm with a PDI of 0.0853 ± 0.0191, indicating a uniform particle size distribution. The encapsulation rate of 4-nBR-NE was determined to be 80.05 ± 0.75 % via UV-Vis spectrophotometry. In addition, 4-nBR-NE demonstrated excellent stability over several months, with negligible changes in particle size. Cellular and transdermal evaluations confirmed that the preparation of 4-nBR-NE effectively reduced the original irritation cause by 4-nBR on cells and skin. Then, 4-nBR-NE was incorporated into an essence. This advancement enhances the applicability of 4-nBR in treating pigmentation disorders such as melasma and freckles, thereby increasing its applicability in pharmaceutical and cosmetic industries.

Fabrication of PLA-Based Nanoneedle Patches Loaded with Transcutol-Modified Chitosan Nanoparticles for the Transdermal Delivery of Levofloxacin.

Current transdermal drug delivery technologies, like patches and ointments, effectively deliver low molecular weight drugs through the skin. However, delivering larger, hydrophilic drugs and macromolecules remains a challenge. In the present study, we developed novel transdermal nanoneedle patches containing levofloxacin-loaded modified chitosan nanoparticles. Chitosan was chemically modified with transcutol in three ratios (1/1, 1/2, 1/3, w/w), and the optimum ratio was used for nanoparticle fabrication via the ionic gelation method. The successful modification was confirmed using ATR-FTIR spectroscopy, while DLS results revealed that only the 1/3 ratio afforded suitably sized particles of 220 nm. After drug encapsulation, the particle size increased to 435 nm, and the final formulations were examined via XRD and an in vitro dissolution test, which suggested that the nanoparticles reach 60% release in a monophasic pattern at 380 h. We then prepared transdermal patches with pyramidal geometry nanoneedles using different poly(lactic acid)/poly(ethylene adipate) (PLA/PEAd) polymer blends of varying ratios, which were characterized in terms of morphology and mechanical compressive strength. The 90/10 blend exhibited the best mechanical properties and was selected for further testing. Ex vivo permeation studies proved that the nanoneedle patches containing drug-loaded nanoparticles achieved the highest levofloxacin permeation (88.1%).

Reconnoitring signaling pathways and exploiting innovative approaches tailoring multifaceted therapies for skin cancer.

Nowadays, skin cancer is widespread just like a varied malignant cancer which can cause serious health issues. Skin cancer, which encompasses malignant melanoma, basal cell carcinoma, and squamous cell carcinoma, is a prevalent form of cancer among humans. Due to its broad prevalence, financial burden, mortality rates, and cosmetic effects, it is a major public health issue. Skin cancer treatment involves surgery, chemotherapy, and radiation. Recently, personalized treatment in the fields of targeted therapies and precision medicine has been shown to diagnose early detection of every individual tumor by knowing their genetic and molecular characteristics. To target the molecular pathways responsible for tumor growth and reduce the damage to healthy tissue, new targeted therapies have emerged for melanoma, basal cell carcinoma, and squamous cell carcinoma. B-raf serine/threonine kinase (BRAF) and mitogen-activated protein kinase (MEK) inhibitors, immune checkpoint inhibitors, and precision medications have strong response rates to improve patient survival. Targeted therapeutics like nanocarriers have shown promising results by reducing skin irritation and protecting encapsulated therapeutics. These formulations have been shown to improve the transdermal permeability of anticancer drugs. The consideration of employing physical techniques to enhance the permeation of nanocarriers warrants attention to augment the dermal permeation of anticancer agents and facilitate targeted drug delivery within neoplastic cells. Targeted therapies face obstacles like resistance mechanisms and treatment strategy monitoring. Taken together, this review delves into the basic mechanisms of skin cancer, current treatment methods, drug resistance processes, and nano-based targeted techniques for cancer treatment. It will also delineate the challenges and perspectives in pre-clinical and clinical contexts.

Mild-photothermal and nanocatalytic therapy for obesity and associated diseases.

Background: Current anti-obesity medications suffer from limited efficacy and side-effects because they act indirectly on either the central nervous system or gastrointestinal system. Herein, this work aims to introduce a transdermal photothermal and nanocatalytic therapy enabled by Prussian blue nanoparticles, which directly act on obese subcutaneous white adipose tissue (sWAT) to induce its beneficial remodeling including stimulation of browning, lipolysis, secretion of adiponectin, as well as reduction of oxidative stress, hypoxia, and inflammation. Methods: Prussian blue nanoparticles were synthesized and incorporated into silk fibroin hydrogel for sustained retention. The efficacy of mild photothermal (808 nm, 0.4 W/cm2, 5 min) and nanocatalytic therapy (mPTT-NCT) was assessed both in vitro (3T3-L1 adipocytes) and in vivo (obese mice). The underlying signaling pathways are carefully revealed. Additionally, biosafety studies were conducted to further validate the potential of this therapy for practical application. Results: On 3T3-L1 adipocytes, mPTT-NCT was able to induce browning, enhance lipolysis, and alleviate oxidative stress. On obese mice model, the synergistic treatment led to not only large mass reduction of the targeted sWAT (53.95%) but also significant improvement of whole-body metabolism as evidenced by the substantial decrease of visceral fat (65.37%), body weight (9.78%), hyperlipidemia, and systemic inflammation, as well as total relief of type 2 diabetes. Conclusions: By directly targeting obese sWAT to induce its beneficial remodeling, this synergistic therapy leads to significant improvements in whole-body metabolism and the alleviation of obesity-related conditions, including type 2 diabetes. The elucidation of underlying signaling pathways provides fundamental insights and shall inspire new strategies to combat obesity and its associated diseases.

Dissolvable microneedle-based wound dressing transdermally and continuously delivers anti-inflammatory and pro-angiogenic exosomes for diabetic wound treatment.

Due to overactive inflammation and hindered angiogenesis, self-healing of diabetic wounds (DW) remains challenging in the clinic. Platelet-derived exosomes (PLT-Exos), a novel exosome capable of anti-inflammation and pro-angiogenesis, show great potential in DW treatment. However, previous administration of exosomes into skin wounds is topical daub or intradermal injection, which cannot intradermally deliver PLT-Exos into the dermis layer, thus impeding its long-term efficacy in anti-inflammation and pro-angiogenesis. Herein, a dissolvable microneedle-based wound dressing (PLT-Exos@ADMMA-MN) was developed for transdermal and long-term delivery of PLT-Exos. Firstly, a photo-crosslinking methacrylated acellular dermal matrix-based hydrogel (ADMMA-GEL), showing physiochemical tailorability, fast-gelling performance, excellent biocompatibility, and pro-angiogenic capacities, was synthesized as a base material of our dressing. For endowing the dressing with anti-inflammation and pro-angiogenesis, PLT-Exos were encapsulated into ADMMA-GEL with a minimum effective concentration determined by our in-vitro experiments. Then, in-vitro results show that this dressing exhibits excellent properties in anti-inflammation and pro-angiogenesis. Lastly, in-vivo experiments showed that this dressing could continuously and transdermally deliver PLT-Exos into skin wounds to switch local macrophage into M2 phenotype while stimulating neovascularization, thus proving a low-inflammatory and pro-angiogenic microenvironment for DW healing. Collectively, this study provides a novel wound dressing capable of suppressing inflammation and stimulating vascularization for DW treatment.

Biological Fate Tracking of Nitric Oxide-Propelled Microneedle Delivery System Using an Aggregation-Caused Quenching Probe.

Nanoparticle-loaded dissolving microneedles (DMNs) have attracted increasing attention due to their ability to provide high drug loading, adjustable drug release behavior, and enhanced therapeutic efficiency. However, such delivery systems still face unsatisfied drug delivery efficiency due to insufficient driving force to promote nanoparticle penetration and the lack of in vivo fate studies to guide formulation design. Herein, an aggregation-caused quenching (ACQ) probe (P4) was encapsulated in l-arginine (l-Arg)-based nanomicelles, which was further formulated into nitric oxide (NO)-propelled nanomicelle-integrated DMNs (P4/l-Arg NMs@DMNs) to investigate their biological fate. The P4 probe could emit intense fluorescence signals in intact nanomicelles, while quenching with the dissociation of nanomicelles, providing a "distinguishable" method for tracking the fate of nanomicelles at a different status. l-Arg was demonstrated to self-generate NO under the tumor microenvironment with excessive reactive oxygen species (ROS), providing a pneumatic force to promote the penetration of nanomicelles in both three-dimensional (3D)-cultured tumor cells and melanoma-bearing mice. Compared with passive microneedles (P4 NMs@DMNs) without a NO propellant, the P4/l-Arg NMs@DMNs possessed a good NO production performance and higher nanoparticle penetration capacity. In conclusion, this study offered an ACQ probe-based biological fate tracking approach to demonstrate the potential of NO-propelled nanoparticle-loaded DMNs in penetration enhancement for topical tumor therapy.

Controlled Transdermal Delivery of Dexamethasone for Pain Management via Photochemically 3D-Printed Bioresorbable Microneedle Arrays.

Microneedle array patches (MAPs) are extensively studied for transdermal drug delivery. Additive manufacturing enables precise control over MAP customization and rapid fabrication. However, the scope of 3D-printable, bioresorbable materials is limited. Dexamethasone (DXM) is widely used to manage inflammation and pain, but its application is limited by systemic side effects. Thus, it is crucial to achieve high local drug concentrations while maintaining low serum levels. Here, poly(propylene fumarate-co-propylene succinate) oligomers are fabricated into DXM-loaded, bioresorbable MAPs via continuous liquid interface production 3D printing. Thiol-ene click chemistry yields MAPs with tailorable mechanical and degradation properties. DXM-loaded MAPs exhibit controlled elution of drug in vitro. Transdermal application of DXM-loaded MAPs in a murine tibial fracture model leads to substantial relief of postoperative pain. Pharmacokinetic analysis shows that MAP administration is able to control pain at a significantly lower dose than intravenous administration. This work expands the material properties of 3D-printed poly(propylene fumarate-co-propylene succinate) copolyesters and their use in drug delivery applications.

Influence of co-solvents on properties of terpene-based eutectic mixtures: Implications for skin delivery.

Terpene-based eutectic mixtures (EMs) are attractive platforms for transdermal delivery due to their solubilizing potential and ability to alter the barrier function of the stratum corneum (SC). Despite this, little is known about the effect of diluting EMs with co-solvents (CSs) on their solubility- and permeation-enhancing properties. Furthermore, insufficient attention has been paid to comparing these platforms with traditional solvents, such as propylene glycol (PG) or ethanol (EtOH). To address this gap, the present study investigates the impact of the CS content in EM:CS blends on the transdermal delivery of clotrimazole (CLOT). Two CSs, PG and EtOH, and two terpene-based EMs, menthol:thymol and thymol:ß-citronellol, were used. Each of the EMs was investigated at two different molar ratios between the terpenes, with one being their eutectic point, to explore its potential benefit for skin permeation. At each step, properties of the blends were compared with those of pure CSs. The EM:CS blends showed a better solubilizing potential for CLOT than EMs or CSs on their own. A higher content of CSs in the blends resulted in a higher skin permeation and retention of CLOT, and a lower degree of disarrangement of the SC structure. Furthermore, the blends of EMs at their EPs led to overall poorer permeation profiles, implying that the permeation rate is more affected by the properties of the individual terpenes than by the specific ratio at the eutectic point between them. In conclusion, addition of CSs to the EMs promotes permeation and retention of CLOT, while reducing the skin impairment caused by the terpenes.

Hansen solubility parameters and quality-by-design oriented optimized cationic nanoemulsion for transdermal drug delivery of tolterodine tartrate.

Tolterodine tartrate (TOT) is a selective anti-muscarinic drug to treat urinary urgency and overactive urinary bladder (OAB) occurring in children, renal disease and elderly patients. Oral delivery is associated with several adverse effects. We addressed HSPiP and QbD (quality by design)-oriented TOT loaded cationic nanoemulsions for transdermal delivery. Hansen solubility parameters (HSP) screened excipients based on theoretical solubility whereas, QbD optimized cationic nanoemulsions (CNE-TOT-6). Formulation characteristic parameters were desirable to execute targeted in vitro drug release and ex vivo permeation profiles. In vitro hemolysis was conducted at varied concentrations whereas, histopathological study supported the safety aspect of CNE-TOT6. A comparative bioavailability was carried out in a rat model. Capmul PG8 (CAP), tween 80, and PEG 400 (polyethylene glycol 400) were screened based on HSP and experimental solubility data. QbD suggested optimized content of CAP, tween 80, and PEG 400 to achieve the lowest value of size (184 nm), maximum % entrapment efficiency (87.2 %), high zeta potential (+32.6 mV), optimum viscosity (47.19 cP), and high extrudability (96 %) as compared to its gel. High gel consistency slowed down the drug release and permeation flux as compared to CNE-TOT6 suspension. Hemocompatible CNE-TOT6 increased pharmacokinetic parameters as compared to the control and gel without causing skin toxicity after application. Thus, HSPiP and QbD oriented cationic nanoemulsions are promising carriers to treat overactive urinary bladder.

Multiple RONS-Loaded Plasma-Activated Ice Microneedle Patches for Transdermal Treatment of Psoriasis.

Cold atmospheric plasma (CAP) is a fledgling therapeutic technique for psoriasis treatment with noninvasiveness, but clinical adoption has been stifled by the insufficient production and delivery of plasma-generated reactive oxygen and nitrogen species (RONS). Herein, patches of air-discharge plasma-activated ice microneedles (PA-IMNs) loaded with multiple RONS are designed for local transdermal delivery to treat psoriasis as an alternative to direct CAP irradiation treatment. By mixing two RONS generated by the air-discharge plasma in the NOx mode and O3 mode, abundant high-valence RONS are produced and incorporated into PA-IMNs via complex gas-gas and gas-liquid reactions. The PA-IMNs abrogate keratinocyte overproliferation by inducing reactive oxygen species (ROS)-mediated loss of the mitochondrial membrane potential and apoptosis of keratinocytes. The in vivo transdermal treatment confirms that PA-IMNs produce significant anti-inflammatory and therapeutic actions for imiquimod (IMQ)-induced psoriasis-like dermatitis in mice by inhibiting the release of associated inflammatory factors while showing no evident systemic toxicity. Therefore, PA-IMNs have a large potential in transdermal delivery platforms as they overcome the limitations of using CAP directly in the clinical treatment of psoriasis.

Comprehensive investigation of niosomal red palm wax gel encapsulating ginger (Zingiber officinale Roscoe): Network pharmacology, molecular docking, In vitro studies and phase 1 clinical trials.

Ginger, a Zingeberaceae family member, is notable for its anti-inflammatory properties. This study explores the pharmaceutical mechanisms of ginger and red palm wax co-extract, developing novel niosomal formulations for enhanced transdermal delivery. Evaluations included physical characteristics, drug loading, in vitro release, network pharmacology, molecular docking, and biocompatibility. The niosomal ginger with red palm wax gel (NGPW) exhibited non-Newtonian fluid properties. The optimized niosome formulation (cholesterol: Tween80: Span60 = 12.5: 20: 5 w/w) showed a high yield (93.23 %), high encapsulation efficiency (54.71 %), and small size (264.33 ± 5.84 nm), prolonging in vitro anti-inflammatory activity. Human skin irritation and biocompatibility tests on 1 % NGPW showed favorable cytotoxicity and hemocompatibility results (ISO10993). Network pharmacology identified potential targets, while molecular docking highlighted high affinities between gingerol and red palm wax compounds with TRPM8 and TRPV1 proteins, suggesting pain inhibition via serotonergic synapse pathways. NGPW presents a promising transdermal pain inhibitory drug delivery strategy.

Fabrication of Hybrid Coated Microneedles with Donepezil Utilizing Digital Light Processing and Semisolid Extrusion Printing for the Management of Alzheimer's Disease.

Microneedle (MN) patches are gaining increasing attention as a cost-effective technology for delivering drugs directly into the skin. In the present study, two different 3D printing processes were utilized to produce coated MNs, namely, digital light processing (DLP) and semisolid extrusion (SSE). Donepezil (DN), a cholinesterase inhibitor administered for the treatment of Alzheimer's disease, was incorporated into the coating material. Physiochemical characterization of the coated MNs confirmed the successful incorporation of donepezil as well as the stability and suitability of the materials for transdermal delivery. Optical microscopy and SEM studies validated the uniform weight distribution and precise dimensions of the MN arrays, while mechanical testing ensured the MNs' robustness, ensuring efficient skin penetration. In vitro studies were conducted to evaluate the produced transdermal patches, indicating their potential use in clinical treatment. Permeation studies revealed a significant increase in DN permeation compared to plain coating material, affirming the effectiveness of the MNs in enhancing transdermal drug delivery. Confocal laser scanning microscopy (CLSM) elucidated the distribution of the API, within skin layers, demonstrating sustained drug release and transcellular transport pathways. Finally, cell studies were also conducted on NIH3T3 fibroblasts to evaluate the biocompatibility and safety of the printed objects for transdermal applications.

Effectiveness, safety, and preference of transdermal insulin compared to subcutaneous insulin in the treatment of diabetes patients: a systematic review of clinical trials.

BACKGROUND: Several studies were performed on transdermal (TD) insulin delivery in vitro and in vivo, and recently, the study groups included a clinical trial in humans. Therefore, this systematic review was conducted to get summary information about the effectiveness, safety, and preferability of TD insulin in comparison with subcutaneous insulin delivery. METHODS: We conducted a thorough search to find studies in the databases Cochrane Library, MEDLINE via PubMed, Web of Science Core Collection, EMBASE, Scopus, Hinari, Medlib, and Magiran until January 2024. We included 18 randomized clinical trials. RESULTS: Although there are various types of TD delivery methods, the TD insulin delivery methods that have undergone clinical trials are the TD patch, micro needle TD insulin delivery, and TD insulin jet injector. Eighteen studies were conducted on TD insulin delivery, which showed either superior or comparable effectiveness, safety, and preferability of TD insulin in comparison with SC insulin. About eleven out of eighteen studies (61.1%) showed more effective blood glucose control than SC delivery, and the remaining seven studies showed comparable effectiveness with SC delivery. Eleven studies (61.1%) showed equal tolerability of TD insulin versus SC insulin, and seven studies (38.9%) showed more tolerability of TD insulin over SC insulin. In most studies, eleven out of eighteen (61.1%) showed a higher preference for TD insulin delivery over traditional SC delivery; sixth out of eighteen (33.3%) showed equal preferability for TD insulin versus SC insulin; and only one study (5.6%) showed that TD insulin delivery was less preferable than SC insulin. CONCLUSION: The review revealed that clinical trials have demonstrated the effectiveness of TD insulin delivery methods such as TD patches, MN-based insulin delivery, and insulin jet injectors compared to traditional SC routes of administration. The studies showed the superior or comparable effectiveness of TD insulin in controlling blood glucose levels. Additionally, TD insulin delivery was found to be equally or more tolerable than SC insulin delivery in all studies. Overall, the majority of studies favored TD insulin delivery over traditional SC delivery methods, highlighting its potential as a preferred option for insulin administration.