Transdermal Drug Delivery Research Articles

Need of ethosomes as a transdermal drug delivery system

Transdermal Drug Delivery (TDD) TDD is a painless method of delivering drugs systemically by applying a drug formulation onto intact and healthy skin. Ethosomes are soft malleable vesicles composed mainly of phospholipids, ethanol (relatively high concentration) and water. In vitro and in vivo skin permeation experiments have shown that ethosomal formulations can improve the penetration of both hydrophobic and hydrophilic compounds when compared to traditional liposomes. Cold method and hot method are the two types of method of preparation of ethosomes. In comparison to traditional liposomes, antigen-loaded ethosomes for transcutaneous immunization against Hepatitis B were synthesized and described, demonstrating better entrapment effectiveness, appropriate size range, and a unilamellar, spherical shape.As a topical medium (gel), ethosomes and liposomes of azelaic acid (an anti-keratinizing agent used in the treatment of acne) were created, and the results showed that ETHOS 40 might be responsible for a larger azelaic acid concentration than ETHOS 20 and liposomes.

A Review: Microneedle Drug Delivery

The various common techniques for transdermal medication delivery include hypodermic needles, topical lotions, and transdermal patches. Because the stratum corneum layer of the skin acts as a barrier for molecules, the action of most therapeutic medicines is restricted, and only a few molecules are able to penetrate and reach the location of action. A novel type of delivery technology known as micro needles aids in improving medication distribution through this channel and addressing the many issues associated with traditional formulations. Because of the problems associated with oral medication delivery methods, transdermal drug administration utilising micro needles is gaining popularity. The possibilities and uses of micro needles are discussed in this review. Micro needles of many sorts can be manufactured, including solid, dissolving, hydrogel, coated, and hollow micro needles. The fabrication process chosen is determined on the kind and material of the micro needle. This technique is now being used in a variety of sectors, including oligonucleotide distribution, vaccine administration, insulin delivery, and even cosmetics.

Facile fabrication of cedrol nanoemulsions with deep transdermal delivery ability and high safety for effective androgenic alopecia treatment

The successful treatment of androgenic alopecia (AGA) hinges on an effective transdermal drug delivery strategy, a challenge that requires urgent attention. In this study, we introduce a novel approach utilizing cedrol nanoemulsions (CD-NEs) for AGA treatment. Our findings demonstrate that cedrol (CD) effectively inhibits the expression of 5α-reductase 2 (5αR2), akin to the FDA-approved drug finasteride, while also surpassing it in terms of promoting cell proliferation. Through formulation optimization, we have developed stable CD-NEs suitable for large-scale production. Experimental and molecular dynamics simulations further reveal that CD-NEs enhance transdermal penetration by altering lipid organization, facilitating CD delivery to deeper skin layers via a trans-epidermal pathway. In vivo studies conducted on AGA model C57BL/6 mice demonstrate that CD-NEs significantly promote hair follicle regeneration, accelerating the transition of hair follicles from the telogen phase to the anagen phase. Moreover, CD-NEs treatment leads to a significant reduction in dihydrotestosterone (DHT) levels in the skin while maintaining stasis levels in serum, underscoring its efficacy in targeting androgenetic pathways with high safety. This comprehensive analysis sheds light on the efficacy and mechanism of action of CD-NEs in hair regeneration, offering valuable insights for future clinical applications in AGA treatment.

Molecular farming expression of recombinant fusion proteins applied to skincare strategies.

This review discusses the current research progress in molecular farming technology in the field of skincare, with an emphasis on molecular farming expression strategies. The strategies of transdermal drug delivery and their advantages are also highlighted. The expression of cosmetically relevant fused proteins has become an important way to enhance the efficacy of the proteins. Therefore, we also discuss the feasibility and strategies for expressing fusion proteins in A. thaliana, specifically the fusion of Epidermal growth factor (EGF) to a cell-penetrating peptide (CPP), in which the production can be greatly enhanced via plant expression systems since these systems offer higher biosecurity, flexibility, and expansibility than prokaryotic, animal and mammalian expression systems. While the fusion of EGF to CCP can enhance its transdermal ability, the effects of the fusion protein on skin repair, melasma, whitening, and anti-aging are poorly explored. Beyond this, fusing proteins with transdermal peptides presents multiple possibilities for the development of tissue repair and regeneration therapeutics, as well as cosmetics and beauty products. As certain plant extracts are known to contain proteins beneficial for skin health, the expression of these proteins in plant systems will better maintain their integrity and biological activities, thereby facilitating the development of more effective skincare products.

Formulation and Evaluation of Acyclovir Loaded Transferosomal Gel for Transdermal Drug Delivery

Background: A carrying structure for targeted transdermal drug delivery is a transferosome. These unique liposomes are made of an edge activator and phosphatidylcholine. The most common antiviral drug is acyclovir, a synthetic nucleotide nucleoside analog derived from guanine. It works well to cure the varicella-zoster virus and the virus that causes herpes simplex (HSV), primarily HSV-1 and HSV-2. But its skin permeability is minimal. Therefore, this work aimed to use transferosomes to prepare acyclovir so that it could pass through the skin's barrier function. Objective: This study uses a 32-factorial factorial design to develop a transferosomal gel containing acyclovir through thin-film hydration method for painless acyclovir delivery services for skin disease treatment. Material and Methods: The independent variables are the amount of phospholipid (X1) and tween 80 (X2), while the dependent variables are particle size (Y1) and percentage entrapment efficiency (Y2). To create an ideal formulation, the produced transferosomes were assessed for particle size, in vitro drug release amount, and entrapment efficiency (EE%). A Carbopol 934 gel basis was prepared using the optimized acyclovir transferosome formulation, and its drug concentration, pH, spreadability, viscosity, and stability were assessed. Results: With small particles ranging from 176.6 to 324.4 nm, the produced acyclovir transferosomes had a high EE% range from 66.34 to 76.42 %. According to the in vitro release study, there is a negative correlation between in vitro release and EE%. The formulation TF5, including 1%w/w of carbopol 940, provides a superior profile of drug absorption in vitro. Consequently, acyclovir can enter the skin as transferosomes and cross the stratum corneum barrier. Conclusion: Acyclovir can be transformed into a transfersomal gel, which will improve antiviral efficacy, get over the skin's protective layer, prevent adverse oral reactions, and eventually improve patient adherence. Keywords: Transferosome, Transdermal drug delivery system, Acyclovir, 32 Fractional factorial design, Carbopol 934

Energy-based methods and nanocarrier-based approaches for melasma treatment

Melasma is a chronic disease caused by excessive melanin production in the skin, affecting the quality of life, especially in women. As a kind of skin hyperpigmentation, it can be caused by sun exposure, genetics, hormones, drugs, or inflammation. Melasma treatment can be effective when the product penetrates well into the skin. As an essential skin barrier, the stratum corneum displays a significant role in topical and transdermal drug delivery. In this regard, numerous strategies have been developed to increase the skin permeability and efficiency of drugs. This review explores energy-based methods and nanocarrier-based approaches for melasma treatment, focusing on enhancing drug delivery to the viable epidermis and overcoming SC. Physical methods have some advantages like increasing the skin penetration and also some drawbacks, including frequent visits, high costs, and the need for advanced equipment and trained operators. Further, these methods are often combined with high energy and special technics. As an emerging physical-based method that could be used to treat patients with multiple medications, microneedle patch is drawing interest due to its ease of use, ability to pinpoint drug delivery, and fewer side effects. In addition, they can penetrate drug molecules into deeper layers of skin and provide more sustainable results compared to conventional methods. Nanocarrier-based systems like transferosome and ethosome (deformable liposomes) are also effective options for skin penetration and treating melasma and skin hyperpigmentation. Despite several benefits, such as high entrapment efficiency, good permeation, and increased bioavailability of drugs through the skin, their stability problems and limitations toward nanoparticle production on an industrial scale are the most significant drawbacks of this method. In the current review, we looked at the articles published between 2010 and August 2023 on energy-based methods and nanocarriers-based approaches have been used to treat melasma.

Dual modules-molecularly imprinted patch-enabled enantioselectively controlled release of racemic drugs for transdermal delivery

Over 90 % of chiral drugs applied in transdermal drug delivery system (TDDS) are racemates, significantly increasing risks of side effects. Herein, we designed a chiral molecularly imprinted patch (CMIP) that achieved enantioselectively controlled release of S-enantiomers (eutomers) and inhibited the release of R-enantiomers (distomers) for transdermal drug delivery. It is composed of chiral pressure sensitive adhesive (PSA) and molecularly imprinted polymers (MIP), showing better transdermal delivery of S-enantiomers than that of R-enantiomers in vitro (1.86-fold) and in vivo (3.74-fold), significantly decreasing the intake of distomers. Additionally, synthesized fluorescent probe enantiomers visualized enantioselective process of CMIP. Furthermore, investigations of molecular mechanism indicated that dependence on spatial conformation was dominant. On one hand, imprinted cavity of MIP with D-isomer and stronger chiral interaction with R-enantiomers led to more specific adsorption. On the other hand, L-isomer of PSA controlled the release of S-enantiomers by multiple interaction including chiral H-bond, π-π interaction and Van der Waals force. Tthus, the innovatively designed transdermal patch with enantioselective ability released eutomers of racemate and simultaneously inhibited release of distomers, significantly improving therapeutical efficiency and avoiding overdose.

Enhanced diclofenac sodium delivery through advanced self-microemulsifying pectin-based transdermal patches

Diclofenac sodium (DCFNa) presents significant challenges in local pain relief due to its poor solubility and limited skin permeability. This study aimed to enhance the solubility and skin permeation of DCFNa by developing DCFNa-loaded self-microemulsifying drug delivery system (SMEDDS) embedded pressure-sensitive adhesive (PSA) patch. The solubility of DCFNa in various solvents was evaluated, and a ternary phase diagram was constructed to optimize the SMEDDS formulation. The transdermal patch, composed of pectin and polyacrylate, was optimized using a simplex lattice experimental design to achieve the desired adhesion strength and to select the most suitable patch for skin drug accumulation study. Clove oil, Tween® 80, and propylene glycol were identified as the appropriate oil, surfactant, and co-surfactant, respectively, for achieving highest DCFNa solubility. The SMEDDS was formed with a ratio of 5:35:60 (oil: Smix [1:1 surfactant: co-surfactant]: water), yielding nano-sized droplets (22.64 ± 0.74 nm) and significantly enhancing DCFNa solubility (329.62 ± 10.16 mg/mL) compared to phosphate buffer (5.03 ± 1.01 mg/mL). The DCFNa-loaded SMEDDS demonstrated a 9-fold increase in skin permeability compared to the DCFNa solution. The optimized PSA patch, containing 20 % pectin and 40 % polyacrylate, exhibited superior tacking and peel strength. Additionally, a 1 % DCFNa-loaded SMEDDS patch delivered twice greater drug accumulation in the skin and showed no skin irritation, maintaining better adhesion for up to 24 h compared to commercial patches.

Modeling of Dissolving Microneedle-Based Transdermal Drug Delivery: Effects of Dynamics of Polymers in Solution.

Dissolving microneedle (DMN)-assisted transdermal drug delivery (TDD) has received attention from the scientific community in recent years due to its ability to control the rate of drug delivery through its design, the choice of polymers, and its composition. The dissolution of the polymer depends strongly on the polymer-solvent interaction and polymer physics. Here, we developed a mathematical model based on the physicochemical parameters of DMNs and polymer physics to determine the drug release profiles. An annular gap width is defined when the MN is inserted in the skin, accumulating interstitial fluid (ISF) from the surrounding skin and acting as a boundary layer between the skin and the MN. Poly(vinylpyrrolidone) (PVP) is used as a model dissolving polymer, and ceftriaxone is used as a representative drug. The model agrees well with the literature data for ex vivo permeation studies, along with the percent height reduction of the MN. Based on the suggested mathematical model, when loading 0.39 mg of ceftriaxone, the prediction indicates that approximately 93% of the drug will be cleared from the bloodstream within 24 h. The proposed modeling strategy can be utilized to optimize drug transport behavior using DMNs.

Ultraflexible liposomes for transdermal delivery of atorvastatin calcium: Rheological and ex vivo evaluation

AbstractOur research aims to explore the possibility of incorporating atorvastatin calcium (ATC) in ultraflexible nanovesicles (UFNVs) to avoid the hepatic first metabolism and enhance its effectiveness as a potential alternative to oral treatment. ATC nanovesicles were developed utilizing the rotary evaporation‐sonication method and assessed in vitro concerning their vesicle diameter, zeta potential (ZP), entrapment efficiency (EE), as well as in vitro release studies. The chosen formulation of ATC‐UFNVs was integrated into a different gel base that was evaluated for content uniformity, pH, spreading ability, viscosity, and rheological behavior. The skin permeation of the prepared nanovesicles was assessed using an ex vivo permeation and confocal laser microscopy images (CLSM). In vitro evaluation of the ATC‐loaded UFNVs showed that the mean diameter of the nanovesicles ranging between 60.84 ± 0.53 nm and 91.68 ± 2.11 nm, the Zeta potential values ranged from of –15.8 ± 0.31 to –25.1 ± 0.81 mV, the EE% were between 84.33 ± 1.94 and 86.53 ± 2.02%, and the ATC release from the formulations was 75.25–90.89%. All release patterns were analyzed kinetically following Higuchi's diffusion approach. Carbapol 934 gel bases containing ATC‐UF exhibited non‐Newtonian pseudo‐plastic flow with thixotropy equal to 2.013 cm2. Ex vivo data showed that ATC‐UFNVs had better penetration compared to free AC. CLSM revealed that the UF‐nanovesicle exhibited stronger and deeper fluorescence signals up to 90 µm depth of permeation in skin versus the rhodamine B‐free solution (50 µm). The transdermal ability of the ATC‐UFNVs gel formulation has been conclusively demonstrated by our research.Practical Applications: The successful development of atorvastatin calcium‐loaded ultraflexible nanovesicles (ATC‐UFNVs) in this study offers promising applications for researchers and healthcare professionals. The ability of these nanovesicles to bypass hepatic first‐pass metabolism and enhance drug delivery to the skin presents a potential alternative to oral administration, which can be associated with gastrointestinal side effects and variable absorption. The findings of this research can be applied in the development of novel transdermal drug delivery systems for the treatment of various cardiovascular conditions. ATC‐UFNVs may be incorporated into topical formulations for the management of hypercholesterolemia, reducing the need for systemic medication. Additionally, the insights gained from this study could be utilized to explore the feasibility of using nanovesicles for the delivery of other lipophilic drugs, expanding their potential therapeutic applications.

A Self-Skin Permeable Doxorubicin Loaded Nanogel Composite as a Transdermal Device for Breast Cancer Therapy.

Modern drug delivery research focuses on developing biodegradable nanopolymer systems. The present study proposed a polymer-based composite nanogel as a transdermal drug delivery system for the pH-responsive targeted and controlled delivery of anticancer drug doxorubicin (DOX). Nanogels have properties of both hydrogels and nanomaterials. The β-cyclodextrin-based nanogels can enhance the loading capacity of poorly soluble drugs and promote a sustained drug release. The β-cyclodextrin-grafted methacrylic acid conjugated hyaluronic acid composite nanogel was successfully synthesized. β-Cyclodextrin was first grafted onto methacrylic acid. The composite nanogel-based drug carrier was prepared by controlled radical polymerization (CRP) of β-cyclodextrin-grafted methacrylic acid with hyaluronic acid. The doxorubicin-loaded carrier was characterized by Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, ultraviolet-visible (UV-vis) spectroscopy, zeta potential analysis, dynamic light scattering (DLS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The drug loading and release efficiencies were carried out at different pH levels. The maximum drug loading and encapsulation efficiencies of the synthesized final nanogel composite material at pH 8.0 were 86.44 ± 2.12 and 96.07 ± 2.01%, respectively. The DOX-loaded final material showed a 90.0 ± 2.6% release percentage of DOX at pH 5.5, whereas at pH 7.4, the release percentage of DOX was observed to be only 35.0 ± 0.3%. In vitro swelling, degradation, hemocompatibility, drug release kinetics, cytotoxicity, apoptosis, cell colocalization, skin irritation, and skin permeation studies, along with in vivo pharmacokinetic studies, were performed to prove the efficacy of the synthesized nanogel composite as a transdermal carrier for doxorubicin.

Fabrication of Poly Lactic-co-Glycolic Acid Microneedles for Sustained Delivery of Lipophilic Peptide-Carfilzomib.

Transdermal drug delivery (TDD) is an attractive route of administration, providing several advantages, especially over oral and parenteral routes. However, TDD is significantly restricted due to the barrier imposed by the uppermost layer of the skin, the stratum corneum (SC). Microneedles is a physical enhancement technique that efficiently pierces the SC and facilitates the delivery of both lipophilic and hydrophilic molecules. Dissolving microneedles is a commonly used type that is fabricated utilizing various biodegradable and biocompatible polymers, such as polylactic acid, polyglycolic acid, or poly(lactide-co-glycolide) (PLGA). Such polymers also promote the prolonged release of the drug due to the slow degradation of the polymer matrix following its insertion. We selected carfilzomib, a small therapeutic peptide (MW: 719.924 g/mol, log P 4.19), as a model drug to fabricate a microneedle-based sustained delivery system. This study is a proof-of-concept investigation in which we fabricated PLGA microneedles using four types of PLGA (50-2A, 50-5A, 75-5A, and 50-7P) to evaluate the feasibility of long-acting transdermal delivery of carfilzomib. Micromolding technique was used to fabricate the PLGA microneedles and characterization tests, including Fourier transform infrared spectroscopy, insertion capability using the skin simulant Parafilm model, histological evaluation, scanning electron microscopy, and confocal microscopy were conducted. In vitro release and permeation testing were conducted in vertical Franz diffusion cells. N-methyl pyrrolidone was utilized as the organic solvent and microneedles were solidified in controlled conditions, which led to good mechanical strength. Both in vitro release and permeation testing showed sustained profiles of carfilzomib over 7 days. The release and permeation were significantly influenced by the molecular weight of PLGA and the lipophilic properties of carfilzomib.

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%).

Emerging Trends in Dissolving-Microneedle Technology for Antimicrobial Skin-Infection Therapies.

Skin and soft-tissue infections require significant consideration because of their prolonged treatment duration and propensity to rapidly progress, resulting in severe complications. The primary challenge in their treatment stems from the involvement of drug-resistant microorganisms that can form impermeable biofilms, as well as the possibility of infection extending deep into tissues, thereby complicating drug delivery. Dissolving microneedle patches are an innovative transdermal drug-delivery system that effectively enhances drug penetration through the stratum corneum barrier, thereby increasing drug concentration at the site of infection. They offer highly efficient, safe, and patient-friendly alternatives to conventional topical formulations. This comprehensive review focuses on recent advances and emerging trends in dissolving-microneedle technology for antimicrobial skin-infection therapy. Conventional antibiotic microneedles are compared with those based on emerging antimicrobial agents, such as quorum-sensing inhibitors, antimicrobial peptides, and antimicrobial-matrix materials. The review also highlights the potential of innovative microneedles incorporating chemodynamic, nanoenzyme antimicrobial, photodynamic, and photothermal antibacterial therapies. This review explores the advantages of various antimicrobial therapies and emphasizes the potential of their combined application to improve the efficacy of microneedles. Finally, this review analyzes the druggability of different antimicrobial microneedles and discusses possible future developments.

Formulation, optimization and evaluation of ibuprofen loaded menthosomes for transdermal delivery

The study aimed to improve the transdermal permeation of IBU utilizing menthosomes as a vesicular carrier. IBU-loaded menthosomes were formulated by thin film hydration & optimized using 23 factorial designs (Design Expert® version 13 software). In vitro &ex vivo skin permeation analysis of IBU-encapsulated menthosomes was studied across the rat skin sample. In vivo pharmacodynamic activity was studied in an arthritis rat model. The optimized IBU-loaded menthosomes exhibited an optimum vesicle size of 214.2 ± 2.96 nm, Zeta potential of −21.1 ± 2.72 mV, (PDI) Polydispersity Index of 0.267 ± 0.018 with Entrapment efficiency (EE%) of 78.7 ± 2.73 %. The in vitro &ex vivo skin penetration study displayed enhanced release of drug of 77.02 ± 1.0 % and 40.91 ± 0.81 % respectively, compared to conventional liposomes. In vivo pharmacodynamic study on carrageenan-induced paw edema in Wistar albino rats demonstrated superior anti-inflammatory activity of the optimized IBU-encapsulated menthosomes (**p < 0.01) and effective inhibition of paw edema (34.04 ± 0.155 %). The formalin test indicated a significant analgesic effect of optimized formulation during the chronic phase of analgesia (*p < 0.05) compared to the control group. Thus, the developed and optimized drug-loaded menthosomes could serve as a suitable vesicular delivery carrier in enhancing the transdermal delivery of other NSAID drugs.

A Comprehensive Review of Nanogel-Based Drug Delivery Systems.

Polymers can be crosslinked chemically or physically to create three-dimensional hydrogel particles with sub-micron dimensions, known as nanogels. Their customizable size, ease of manufacture, expansion potential, bio-integration, water affinity, and reactivity to various stimuli, including temperature, pH, light, and biological agents, provide them with considerable advantages over conventional drug delivery techniques. Nanogels possess properties of both hydrogels and nanoparticles and can be categorized into nanohydrogels and nano-organogels. These systems exhibit exceptional drug-loading capability, stability, biological consistency, and environmental responsiveness. Their hallmark lies in their swelling behavior, enabling substantial water absorption while maintaining structural integrity. Preparation methods involve polymer precursors or heterogeneous polymerization of monomers. Nanogels are promising for various drug administration techniques, including local anesthetics, vaccines, and transdermal drug delivery, due to their ability to encapsulate multiple bioactive ingredients, enhancing therapeutic efficacy and stability.

Hyaluronate functionalized Span-Labrasol nanovesicular transdermal therapeutic system of ferulic acid targeting diabetic nephropathy

Diabetic kidney disease, known as diabetic nephropathy (DN), is a widespread severe diabetes complication leading to kidney failure. Due to the lack of efficacious therapies, this study endeavors to enhance DN therapeutic effectiveness of ferulic acid (FRA), a natural phenolic with poor oral bioavailability, by developing a transdermal kidney-targeted spanlastic formulation. Spanlastics (SP) nanovesicles were prepared using Span 60 and Labrasol or Brij35 as edge activators (EA). Cationic guar (CG) and hyaluronic acid (HA) were employed as coatings. The formulations were assessed for entrapment efficiency (EE), particle size (PS) and zeta potential (ZP). A 21 × 31 factorial optimization of FRA spanlastic formulations revealed the desirable nanoformula was FRA-L-H-SP comprising Labrasol and hyaluronate coating. Transmission electron microscopy (TEM), Fourier-transform infrared (FT-IR), Diphenylpicrylhydrazyl (DPPH) antioxidant activity, in-vitro release, and rat skin ex-vivo permeation assessed this formula and the uncoated one (FRA-L-SP). Biochemical indicators and histopathology for diabetes and kidney injury were evaluated in the Streptozotocin (STZ)-induced DN rat model. Results showed significant improvements after treatment with FRA-L-H-SP compared to FRA-L-SP and free FRA, with decreased blood glucose, creatinine, and intercellular adhesion molecule-1 (ICAM-1) levels and increased insulin, AMP-activated protein kinase (AMPK), and sirtuins (SIRT). This enhancement can be acknowledged as passive targeting of SP and active targeting properties of hyaluronic to cluster of differentiation 44 (CD44) receptors, revealing the potential to improve DN pathophysiology.

A Multicomponent Microneedle Patch for the Delivery of Meloxicam for Veterinary Applications.

This study evaluates the use of poly(vinyl alcohol), collagen, and chitosan blends for developing a microneedle patch for the delivery of meloxicam (MEL). Results confirm successful MEL encapsulation, structural integrity, and chemical stability even after ethylene oxide sterilization. Mechanical testing indicates the patch has the required properties for effective skin penetration and drug delivery, as demonstrated by load-displacement curves showing successful penetration of pig ear surfaces at 3N of normal load. In vitro imaging confirms the microneedle patch penetrates the pig's ear cadaver skin effectively and uniformly, with histological evaluation revealing the sustained presence and gradual degradation of microneedles within the skin. Additionally, in vitro drug diffusion experiments utilizing ballistic gel suggest that microneedles commence dissolution almost immediately upon insertion into the gel, steadily releasing the drug over 24 h. Furthermore, the microneedle patch demonstrates ideal drug release capabilities, achieving nearly 100% release of meloxicam content from a single patch within 18 h. Finally, in vivo studies using pigs demonstrate the successful dissolution and transdermal drug delivery efficacy of biodegradable microneedle patches delivering meloxicam in a porcine model, with over 70% of microneedles undergoing dissolution after 3 days. While low detectable meloxicam concentrations were observed in the bloodstream, high levels were detected in the ear tissue, confirming the release and diffusion of the drug from microneedles. This work highlights the potential of microneedle patches for controlled drug release in veterinary applications.

Is personal physiology-based rapid prediction digital twin for minimal effective fentanyl dose better than standard practice: a pilot study protocol

IntroductionPatients with advanced cancer frequently suffer from chronic, severe disabling pain. Opioids such as morphine and fentanyl are commonly used to manage this pain. Transdermal drug delivery systems are important...

Effect of Triton X-100 surfactant and agitation on tetramethylammonium hydroxide wet etching for microneedle fabrication

Solid silicon (Si) microneedles have many applications such as skin pretreatment to form micrometer-sized holes in the skin surface in transdermal drug delivery systems. Wet etching based on tetramethylammonium hydroxide (TMAH) is an efficient method to fabricate solid microneedles. However, it is challenging to increase the density of microneedle arrays due to the faster lateral etching than the vertical etching that requires a large initial mask size. In this work, we used wet etching based on TMAH to fabricate solid Si microneedles. One kind of nonionic surfactant, Triton X-100, was introduced into the TMAH solution to suppress the lateral etching. When Triton X-100 was added into TMAH for a given etching condition, the maximum height (attained right before the mask fell off) of microneedles could reach ∼230 μm for 600 μm square-shaped mask size and 700 μm array period, compared to microneedles of maximum 152 μm height for the same mask size and period without surfactant addition. Correspondingly, when the target heights of microneedles were the same as ∼230 μm, denser (down to 700 μm period, 600 μm mask size) microneedle arrays were achieved with the help of Triton X-100, in comparison to arrays down to 900 μm period (800 μm mask size) without surfactant addition. Furthermore, agitation by a magnetic stirring bar is important for the fabrication of dense solid Si microneedle arrays based on TMAH. The microneedle structures were rhombic pyramid in shape with Triton X-100 and agitation. But microneedle structures obtained with Triton X-100 yet without agitation were octagonal pyramid in shape with a much less steep side surface.