Atorvastatin-Loaded Dissolving Microarray Patches for Long-Acting Microdepot Delivery: Comparison of Nanoparticle and Microparticle Drug Formulations.

The increasing popularity of prolonged-release dosage forms, owing to their ability to provide continuous drug release after administration, has significantly improved patient compliance and overall quality of life. However, achieving prolonged release beyond 24 h frequently requires the use of invasive methods, including injections or implants, which may prove challenging for people suffering from needle phobia. This study introduces atorvastatin (ATR) microparticles (MPs) or nanocrystal (NCs) dissolving microarray patches (D-MAPs) as a noninvasive alternative for intradermal drug delivery over a two-week period for the management of hyperlipidemia. The MP-loaded D-MAPs exhibited an average drug loading of 5.15 ± 0.4 mg of ATR per patch, surpassing the 2.4 ± 0.11 mg/patch observed with NC-loaded D-MAPs. Skin deposition studies demonstrated the superior performance of MP D-MAPs, which delivered 2.0 ± 0.33 mg of ATR per 0.75 cm2 patch within 24 h, representing 38.76% of the initial amount of drug loaded. In contrast, NC D-MAPs delivered approximately 0.89 ± 0.12 mg of ATR per 0.75 cm2 patch at 24 h, equivalent to 38.42 ± 5.13% of the initial ATR loaded. Due to their favorable results, MP D-MAPs were chosen for an in vivo study using Sprague-Dawley rats. The findings demonstrated the capacity of D-MAPs to deliver and attain therapeutically relevant ATR concentrations (>20 ng/mL) for 14 days after a single 24-h application. This study is the first to successfully demonstrate the long-acting transdermal delivery of ATR using MP-loaded D-MAPs after a 24-h single-dose application. The innovative D-MAP system, particularly when loaded with MP, arises as a promising, minimally invasive, long-acting substitute for ATR delivery. This technology has the potential to improve patient compliance and therapeutic outcomes while also significantly advancing the field of transdermal drug delivery.

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.

A finasteride patch for the treatment of androgenetic alopecia: A study of promoting permeability strategy using synthetic novel O-acylmenthols combined with ion-pair.

Currently, finasteride (FIN) is approved to treat androgenetic alopecia only orally, and the application of FIN in transdermal drug delivery system (TDDS) has introduced a new approach for treating the disease. This study was aimed to develop a FIN transdermal patch for the treatment of androgenetic alopecia（AGA） by combing ion-pair and O-acylmenthols (AM) as chemical permeation enhancers (CPEs). The formulation of patch was optimized though single-factor investigation and Box-Behnken design. The pharmacokinetics and androgenetic alopecia pharmacodynamics of the patch were evaluated. Additionally, the permeability enhancement mechanisms of ion-pair and AMs were explored at both the patch and skin levels. The effects of ion-pair and AMs on the patch were characterized by rheology study, FTIR, and molecular docking, and the effects on the skin were assessed through ATR-FTIR, Raman study, DSC, CLSM and molecular dynamics. The finalized formulation of FIN patches was consisted of 5 % (w/w) synthetic FIN-CA (Citric Acid), 6 % MT-C6 as CPEs, 25-AAOH as a pressure-sensitive adhesive (PSA), with a patch thickness of 80 ± 5 µm. The final Q24 h is 78.22 ± 5.18 µg/cm2. Based on the high FIN permeability, the pharmacokinetic analysis revealed that the FIN patch group exhibited a slower absorption rate (tmax = 7.3 ± 2.7 h), lower peak plasma concentration and slower metabolic rate (t1/2 = 6.2 ± 0.8 h, MRT0-t = 26.0 ± 7.8 h) compared to the oral group. Moreover, the FIN patch also demonstrated the same effect as the oral group in promoting hair growth in AGA mice. The results indicated that both FIN-CA and AMs could enhance the fluidity of the PSA and weaken the interaction between FIN-CA and PSA, thereby promoting the release of the FIN from the patch. The interaction sites on the skin for ion-pair and the four AMs were found in the stratum corneum (SC) of the skin, disrupting the tight arrangement of stratum corneum lipids. This study serves as a reference for the multi-pathway administration of FIN and the combination of ion-pair with AMs to enhance drug permeation.

Efficacy of Transdermal Buprenorphine Patch in Postoperative Pain Management in Oral and Maxillofacial Surgery.

Aim: To evaluate the therapeutic efficacy of transdermal Buprenorphine patch in postoperative pain management in Major Oral and Maxillofacial surgeries done under general anesthesia. Materials and Method: A total number of 100 subjects, both males and females in the age group of 18-60 years were included in the study. At the screening visit, a brief medical history was recorded for each prospective subject. The subject was selected according to the inclusion and exclusion criteria and consent was taken before placing the patch. For a period of 7 days, 10 mg Buprenorphine patch was placed on the skin of the patient for 3 h before the surgery. Analgesic efficacy was recorded for the next 7 days by using visual analogue scale (hereinafter refered to as "VAS"). If the VAS score was above 5, the rescue analgesia inj. Dynapar I.V was administered to the patient. Results: The mean VAS score in females 4.4, was high when compared to males 3.9, which would suggest that the patch was more effective in males compared to females. Trauma patients showed mean VAS score of 3.9 and pathology patients showed a mean VAS score of 4.1. 36% of the patients required additional analgesics as the VAS score was more than 5. 20% of patients between age group of 20-30 years required additional analgesics, 66.7% in 31-40yrs, 0% of 41-50yrs and 13.3% in 51-60yrs required additional analgesics. 24% of the females patients required 37 additional analgesics compared to the 12% in male patients. 21.6% of patients treated for pathology required additional analgesics compared to the 8.2% in trauma patients. Thus, the sensitivity of this study was 94.1% and specificity was 33.3%. Conclusion: Buprenorphine has high analgesic potential, good safety profile, ease of opioids switches and reversibility by µ- antagonist. Transdermal route is cost effective and has increased patient compliance and ease of handling with less adverse effects. Thus, the efficacy of transdermal buprenorphine in postoperative pain management was good.

Iodine Deficiency as a Risk Factor for Postpartum Depressive Disorder in Women.

Nutritional support is considered as one of the components of disease-modifying therapy for postpartum depressive disorder. Such nutrients include iodine, which is an important trace element in the development and functioning of the central nervous system. The brief review presents updated knowledge about the relationship of iodine deficiency with the development and severity of postpartum depressive disorders in women, based on the analysis and generalization of the results of domestic and international studies.

The molecular design of novel phospholipid-inspired ionic liquid transdermal penetration enhancers: Innovative insights on the action mode and mechanism.

Ionic liquid transdermal penetration enhancers (IL@TPEs) as new enhancement methods have significant advantages in the transdermal drug delivery system. However, the scientific frameworks for the design of efficient IL@TPEs and their applications in transdermal formulations were still lack. So, a series of novel biomimetic phospholipid-inspired IL@TPEs (PIL@TPEs) were designed and synthesized. The developed QSARs proved that enhancement efficacy of PIL@TPEs depended on pKa of drugs and M.W., Polar., and pKa of cations. Surprisingly, the PIL@TPEs dissociated during transdermal process, and skin penetration amounts of acidic drugs was inversely proportional to skin retention amounts of cations, which showed that action modes of PIL@TPEs were different from conventional enhancers. The novel mechanisms of PIL@TPEs were elucidated by quantitative determination of dynamic interaction among cations, anions, drugs, and skins. The PIL@TPEs with high enhancement efficiency owned strong interactions with drugs determined by ATR-FTIR, Raman and NOESY. Moreover, the PIL@TPEs owning better stability in skin ensured the production of strong interactions with lipids and keratins characterized by ATR-FTIR, 1H NMR and CLSM. The good safety of optimized PIL@TPEs was proved by determining cytotoxicity, apoptosis, inflammatory cells, and cytokines. In conclusion, this project will make an important contribution to the design and application of IL@TPEs.

Assessment of basic pharmacokinetic parameters of dapagliflozin in TTS formulations in male minipigs.

Given the extended time over which diabetes treatment is administered, the transdermal delivery system is anticipated to be a more suitable option for older individuals who may experience difficulty swallowing. The continuous delivery of dapagliflozin and more stable plasma levels are anticipated to reduce the incidence of side effects and the frequency of dosing. The objectives of the study were to determine the safety and plasma pharmacokinetics of dapagliflozin in male minipigs following application of the ointment and skin patch. In the initial phase of the study, the potential for transdermal permeation of dapagliflozin from ointment and transdermal patch to blood plasma of 15 male Göttingen minipigs was investigated. In the subsequent phase, the efficacy of utilising patches of varying strengths and sizes was assessed. The LC/MS method was employed to quantify the concentration of the active substance. The transportation of the studied API to the general circulation and accumulation in tissues were confirmed. The maximum drug concentration (122.99 ng/mL) in plasma was observed on the fourth day of application. The highest calculated Cmax was 131.91 ng/mL with a mean AUC0-last of 6620.7 ng h/mL. Following transdermal administration, dapagliflozin is excreted in the urine. The trend between urinary dapagliflozin 3-O-glucuronide levels and urinary glucose excretion was also observed. The transdermal patch has been demonstrated to be an effective drug delivery system for dapagliflozin.

Transdermal Drug Delivery Systems (TDDS): Recent Advances and Failure Modes.

Transdermal drug delivery systems (TDDS), commonly refered to as "patches", present a nonintrusive technique to provide medication without the need for invasive procedures. These products adhere to the skin and gradually release a specific dosage of medicine at a defined rate into the bloodstream. Compared with other methods of drug delivery, TDDS offer benefits such as reduced invasiveness, convenience for patients, and avoidance of the metabolic processes that occur when drugs are orally consumed. Throughout time, TDDS have been used to provide medications for various medical conditions (such as nicotine, fentanyl, nitroglycerin, and clonidine), and their potential for delivering biologics is currently being explored. This review investigates the current literature on the drug delivery efficacy of medical TDDS through the transdermal route. Additionally, the review addresses potential risks and failure modes associated with TDDS design and development as well as strategies for mitigating such risks. A thorough understanding of failure modes provides a blueprint to mitigate failure and produce high-quality efficacious therapeutics.

Polymer homologue-mediated formation of hydrogel microneedles for controllable transdermal drug delivery.

Poly(ethylene glycol) diacrylate (PEGDA) microneedles (MNs) are hydrogel-based devices that achieve controlled drug delivery kinetics by adjusting the crosslinking density. However, the biosafety of many crosslinking agents used to regulate crosslinking density is not ideal. To avoid crosslinking agents and simplify the preparation process, using two types of polymer homologues with different number-average molecular weights, we have successfully developed a series of PEGDA MNs with controllable crosslinking density (abbreviated as TP-X MNs). The research showed that the mechanical properties and drug release behavior of TP-X MNs could be tuned by simply controlling the weight proportion of two different PEGDA components in MNs. Ex vivo drug delivery experiments indicated that all TP-X MNs exhibited a sustained release profile, and their control range of 336-hour accumulative release rates was from 6.24% to 40.93%. Moreover, we prepared a novel dual-layer PEDGA MN, which can customize the drug loading and release rate in each layer of MN. This work demonstrates a new way to develop hydrogel MNs with adjustable crosslink density and broadens the applications of PEGDA MN in the biomedical field.

Reusable and non-invasive TiO2-based photodynamic transdermal patch (RPT) for treating MDR-negative bacteria strain and promote wound healing through a synergistic approach of ROS-induced RNS.

Wound healing is delayed due to the infection and biofilm formation of antibiotic-resistant species of gram-negative bacteria especially Pseudomonas aeruginosa and Escherichia coli. Antibacterial photodynamic therapy provides an efficient therapeutic strategy for overcoming drug resistance by producing reactive oxygen species (ROS) and reactive nitrogen species (RNS). Here, we have designed a low-cost light emitting diode (LED) based reusable and non-invasive titanium dioxide nanoparticles patch which is sandwiched between the thin polymer layers. The light-induced pore formation in the polymeric film due to the free radical, in turn, passes through the system and kills the bacteria rather than nanoparticles entering the system resulting in the reusability nature of the patch. The patch's in vitro antibacterial and antibiofilm activity and their mechanism (synergic ROS-induced RNS) were studied. In addition, the reusable antibacterial properties, biocompatibility and wound-healing properties of the patch were also successfully elucidated.

A Self-Assembled Transdermal Nanomedicines Incorporating Pendant Disulfides for Non-Invasive, Synergistic Treatment of Melanoma.

Transdermal drug delivery system (TDDS) offers lower systemic toxicity and good patient compliance, making it a promising treatment option for skin-related cancers. However, physiological barriers in the skin frequently impede the therapeutic efficiency of TDDS. To address this, a unique self-assembled TDDS that incorporates disulfide pendant groups (termed Sup-TDDS) is presented. It is formulated with dithiolane-containing lipoic acid (LA), photosensitizers Ce6, and chemotherapeutic agents trametinib. Pendant disulfide moieties on Sup-TDDS facilitate thiol-disulfide exchange reactions with exofacial thiols on cell surfaces, thus enhancing stratum corneum penetration. In contrast to intravenous injection, topical administration of Sup-TDDS can penetrate deeper into the skin (> 500 µm) and promote drug accumulation in subcutaneous tumors. In a B16F10-bearing mouse model, Sup-TDDS treatment demonstrates significant anti-tumor effects in primary and recurrent melanoma, benefiting from the synergistic effects of Ce6 and trametinib. These results underscore that Sup-TDDS's transdermal properties allow non-invasive melanoma therapy, implying the potential of nanodrugs containing pendant disulfides for transdermal treatment of skin illnesses.

Synthesis of vitamin D3 loaded ethosomes gel to cure chronic immune-mediated inflammatory skin disease: physical characterization, in vitro and ex vivo studies.

The purpose of the current work was to develop and characterize ethosomes of vitamin D3 gel that could more effectively work against psoriasis. Psoriasis is a chronic immune-mediated inflammatory skin disease. Due to vitamin D3 role in proliferation and maturation of keratinocytes, it has become an important local therapeutic option in the treatment of psoriasis. In this research we have initiated worked on ethosomes gels containing vitamin D3 to treat psoriasis. Soya lecithin 1-8% (w/v), propylene glycol and ethanol were used to create the formulations, which were then tested for vesicle size, shape, surface morphology, entrapment effectiveness, and in vitro drug permeation. The drug encapsulation efficiency of ethosomes was 96.25% ± 0.3. The particle sizes of the optimized ethosomes was 148 and 657 nm, and the PDI value was 0.770 ± 0.12 along with negative charge - 14 ± 3. Fourier transform infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC) along with thermogravimetric analysis (TGA) studies confirmed the absence of interactions between vitamin D3 and other ingredients. It was determined that the total amount of medication that penetrated the membrane was 95.34% ± 3. Percentage lysis was very negligible for all strengths which were found less than 15%. Based on our research, ethosomes appear to be safe for use. The vitamin D3 ethosomal gel order, description, pH, and viscosity were all within the specified ranges, according to the findings of a 6-month investigation into the stability profile of the completed system. In this research, we successfully prepared ethosomes loaded with vitamin D3 and then converted it into gel for patients' easy applications.

Facile fabrication of degradable, serrated polyethylene diacrylate microneedles using stereolithography.

Microneedles have the potential for minimally invasive drug delivery. However, they are constrained by absence of rapid, scalable fabrication methods to produce intricate arrays and serrations for enhanced adhesion. 3D printing techniques like stereolithography (SLA) are fast, scalable modalities but SLAs require non-degradable and stiff resins. This work attempts to overcome this limitation by utilizing a poly (ethylene glycol diacrylate) (PEGDA, F3) resin and demonstrating its compatibility with a commercial SLA printer. FESEM images showed high printing efficiency of customized bioinks (F3) similar to commercial resins using SLA 3D printer. Mechanical endurance tests of whole MNA showed that MNs array printed from F3 resin (485 ± 5.73 N) required considerably less force than commercial F1 resin (880 ± 32.4 N). Penetration performance of F1 and F3 was found to be 10.8 ± 2.06 N and 0.705 ± 0.03 N. In-vitro degradation study in PBS showed that MNs fabricated from F3 resin exhibited degradation after 7 days, which was not observed with the commercial F1 resin provided by the manufacturer. The histology of porcine skin exhibited formation of triangular pores with pore length of 548 µm and efficient penetration into the deeper dermal layer. In conclusion, PEGDA can be used as for fabricating degradable, serrated solid MNs over commercial resin.

Optimization, Formulation, and Ex vivo Evaluation of Solid Lipid Nanoparticles for Transdermal Delivery of Diltiazem Hydrochloride.

BACKGROUND: Cardiac arrhythmia, is a medical condition that reduces the heart's efficiency in pumping blood, and can be fatal, requires long-term management with conventional drugs, despite their limited efficacy. Diltiazem hydrochloride, chosen as a model drug, has a short biological half-life and extensive metabolism. Administering drug through skin is challenging, particularly due to the penetration via stratum corneum. However, solid lipid nanoparticles as a particulate carrier system can enhance its permeation and bioavailability. OBJECTIVE: The study aimed to develop a matrix type transdermal patch with diltiazem hydrochloride encapsulated in solid lipid nanoparticles Methods: The study used the solvent diffusion technique to prepare SLNs by mixing the drug and solid lipid in an organic phase at 80°C, then slowly adding it to an aqueous phase with continuous stirring for 45 minutes. The resulting nanodispersion was freeze-dried and analyzed for morphological studies, encapsulation efficiency & drug content. A patch was formulated using solvent evaporation technique, incorporating HPMC E50 (2% w/v), propylene glycol, and ethanolic oleic acid (1.5% v/v). SLNs loaded with diltiazem hydrochloride taken equivalent to diltiazem hydrochloride dose in the transdermal patch. The patch was then evaluated for In vitro and skin permeation studies. RESULTS: The result showed a positive correlation between lipid concentration and particle size. Probe sonication and homogenization increased particle size, while stirring speed reduced it. SEM and TEM images confirmed spherical particles with a size of 488.1±4.01nm and an entrapment efficiency of 55.03±1.99%. Drug release studies demonstrated 70.7% drug release from lipid matrix over 24 hrs. The formulated patch with uniform SLN distribution, had a drug content 89.37 ± 0.04% with a surface pH of 6.1 ± 0.53, close to skin pH. The uniformity of content in 3x3 patch estimated to be 14.587 ± 1.404 mg, close to the theoretical content 16.318 ± 1.08 mg, confirmed homogenous distribution of diltiazem hydrochloride SLNs throughout the patch diameter. Cumulative amount released from patch formulation at pH 5.6 and pH 7.4 was 518.1414µg/cm2 and 404.4466 µg/cm2. Synergistic flux enhancement was observed with oleic acid propylene glycol blend. Ex vivo study of the patch showed steady-state flux of 6.9 µg/cm2/hr, permeability coefficient 0.00362 cm/hr, diffusion coefficient 0.000103 cm/hr, cumulative drug permeation (Dmax) 814.885 µg after 24 hrs, and followed a Higuchi-matrix release model. CONCLUSION: The developed patch possessed improved bioavailability with reduced dosing and enhanced patient compliance.

Visualizing the transdermal delivery of berberine loaded within chitosan microneedles using mass spectrometry imaging.

Berberine (BR), an alkaloid isolated from the Chinese traditional medicine Coptidis rhizoma, exhibits therapeutic effects on several diseases including bacterial infections, diabetes, and hyperlipidemia, but the oral availability is poor. In this work, we prepared the chitosan microneedle array-loaded BR (BR-CS MNAs) to transdermally deliver BR, and the spatial distribution of BR in heterogeneous skin tissues was analyzed and imaged by matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). Some endogenous phospholipids with specific spatial distribution were used to differentiate the epidermis and dermis regions of the skin. The results showed that BR was effectively delivered and could permeate to both epidermis and dermis regions of the skin. This demonstrated the feasibility of MALDI-MSI to evaluate the transdermal delivery efficiency of microneedle arrays and suggested BR could be transdermally delivered by CS MNAs.

Quantifying skin permeation of a novel metformin lotion using modified hydrophilic interaction liquid chromatography.

Aim: This study aimed to quantify the permeation of metformin (Met) lotion through pig ear skin using high-performance liquid chromatography, specifically hydrophilic interaction liquid chromatography (HILIC), to separate Met from biological contaminants and effectively measure its permeation through skin similar to human skin.Materials & methods: A Franz cell permeation assay was used to assess the permeation kinetics of 6% Met lotion through pig ear skin. Samples were collected at various time points and prepared for high-performance liquid chromatography analysis by removing large biological contaminants. The permeated Met was quantified by monitoring its retention time (RT) at 9 min using HILIC, with an acidic, polar mobile phase and a normal-phase column.Results: A distinct Met peak with a RT of approximately 9 min was observed in the 6% Met lotion, which was absent in the permeation samples from the 0% Met lotion. This peak (RT 9 min) was distinct from the 'biological-contaminants' peaks at RT 2-3 min and increased linearly over time, reaching 36.8% of the total applied Met at 24 h.Conclusion: These findings demonstrate that the HILIC method effectively separates Met from biological components in pig ear skin, allowing accurate quantification of Met despite the presence of skin lipids and proteins.

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Strategies for transportation of peptides across the skin for treatment of multiple diseases.

An established view in genetic engineering dictates an increase in the discovery of therapeutic peptides to enable the treatment of multiple diseases. The use of hypodermic needle for delivery of proteins and peptides occurs due to the hydrophilic nature, sensitivity toward proteolytic enzymes and high molecular weight. The non-invasive nature of the transdermal delivery technique offers multiple advantages over the invasive route to release drugs directly into the systemic circulation to enhance bioavailability, better patient compliance, reduced toxicity and local irritability. The transdermal route seems highly desirable from the pharmaco-therapeutic and patient compliance point of view, however, the lipophilic barrier of skin restricts the application. The use of several techniques like electrical methods (iontophoresis, sonophoresis etc.), chemical penetration enhancers (e.g. protease inhibitors, penetration enhancers, etc.) and nanocarriers (dendrimers, lipid nanocapsules, etc.) are utilized to improve the passage of drug molecules across the biomembranes. Additionally, such clinical interventions facilitate the physicochemical characteristics of peptides, to enable effective preservation, conveyance and release of therapeutic agents. Moreover, strategies ensure the attainment of the intended targets and enhance treatment outcomes for multiple diseases. This review article focuses on the techniques of peptide transportation across the skin to advance the delivery approaches and therapeutic efficiency.

[Box: see text].

Transdermal buprenorphine patch as an adjunct to multimodal analgesia after total joint arthroplasty: a retrospective cohort study.

Background: Total hip arthroplasty or total knee arthroplasty (THA/TKA) is often associated with varying degrees of pain. In recent years, transdermal buprenorphine (TDB) patch has shown encouraging results for acute postoperative pain control in orthopedic surgery. The aim of our study was to investigate the efficacy and safety of the combination of TDB patch and nonsteroidal anti-inflammatory drugs (NSAIDs) as a multimodal analgesic regimen after THA/TKA. Methods: Patients who underwent THA and TKA between January 2022 and January 2023 were reviewed. Three postoperative analgesic regimens were selected: Group A (flurbiprofen 50 mg and tramadol 37.5 mg/acetaminophen 325 mg), Group B (flurbiprofen 50 mg and TDB 5 mg), and Group C (Parecoxib 40 mg and TDB 5 mg). The primary outcomes were the Wong-Baker face pain scale revision (FPS-R) scores and the rate of sleep disturbances. Secondary outcomes of the study included the proportion of patients with postoperative pain relief rates categorized as 0%, <50%, ≥50%, and 100%. Results: The dynamic FPS-R pain scores on day 3 after surgery in Group B were significantly lower than those in Group A for THA (P < 0.017). The dynamic FPS-R pain scores were lowest in Group C on day 2 and 3 after THA and TKA (P < 0.017). Rate of sleep disturbances was significantly lower in Group B for THA and in Group C for TKA, respectively, compared with that in Group A (P < 0.017). The proportion of dynamic pain relief rate ≥50% in Group C was statistically higher than that in Group A for THA (P < 0.017). Rate of adverse reactions among three groups for THA and TKA was not statistically different (P > 0.05). Conclusion: This study suggests that the combination of TDB patch and NSAIDs is safe and effective for postoperative analgesia after THA/TKA.

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.

Transdermal carbon dioxide may accelerate hoof growth in healthy, sound horses in a short-term, randomized, controlled clinical trial.

OBJECTIVE: Slow hoof growth poses a clinical challenge when hoof wear exceeds natural growth. Many treatment options have been reported without controlled prospective trials. The objective of this study was to evaluate the effect of transdermal CO2 on the rate of growth in treated hooves. METHODS: A prospective, randomized, blinded, crossover study of 14 Warmblood mares. Horses were randomly assigned a number and allocated for treatment of the front feet with room air or CO2 for 30 minutes 3 times per week, and groups were switched after 5 weeks. Hoof growth was measured on the dorsal midline and the quarters of each front foot. The distance from coronary band to lines made on the hoof wall was measured at the beginning, middle, and end of the study. The percentage of change in length at each location relative to baseline was evaluated at 5 weeks and 10 weeks using nonparametric analyses. RESULTS: All treatments were successfully administered. The left front medial (P = .028) and right front lateral (P = .03) sites of the CO2-treated hooves increased growth compared to the room air group at the 5-week point. CONCLUSIONS: The results of this study suggest that repeated, noninvasive transdermal application of CO2 may accelerate hoof growth in normal horses over a 5-week treatment period. CLINICAL RELEVANCE: This study suggests that transdermal CO2 may increase the rate of hoof growth in normal horses. The mechanism of action of this treatment is unclear, and further studies are required to fully elucidate the potential effects.