Search

Microneedles are an emerging class of transdermal drug delivery systems for biomedical applications. These devices allow minimally invasive and painless drug delivery, making them an attractive alternative to hypodermic injections. This paper focuses on the study of polymer‐based solid microneedles fabrication process using the fused deposition modeling (FDM) method. Biodegradable and biocompatible polymers are selected as printing materials. For this study, the thermoplastic polylactic acid (PLA), currently used for FDM microneedle preparation was selected. To overcome the potential brittleness of PLA during transdermal application, two other materials are also studied: polycaprolactone (PCL) and a PLA/PCL blend. The effect of 3D printing parameters on the dimensional accuracy of the microneedles is studied to determine the optimum printing conditions for each filament. In addition, the dimensions and/or geometry of the microneedles are modified to print its with minimal dimensions. Then, a post‐fabrication chemical etching treatment is used to improve both, size and shape of the printed solid microneedles. [ABSTRACT FROM AUTHOR]

Cannabidiol (CBD) is a non-psychotropic cannabinoid with multiple pharmacological properties. Cannabidiol has attracted growing attention in the cosmetic industry, with an increasing number of CBD-containing skincare products on the market in recent years. The aim of this review is to evaluate the current evidence on the use of CBD for cosmetic purposes. Following an overview of CBD and the endocannabinoid system in the skin, we summarize pre-clinical and clinical studies that address the potential of CBD in cosmetic dermatology. Available in vitro and in vivo evidence suggests that CBD has anti-oxidant, anti-inflammatory, moisturizing, anti-acne, wound-healing, and anti-aging properties. However, only a few clinical studies have been conducted on the use of CBD in the skin. In addition, there is a critical need to develop an efficient drug-delivery system for topical/transdermal application of CBD. Further research, including clinical and pharmacokinetic studies, are needed to fully evaluate the role of CBD in cosmetic dermatology. [ABSTRACT FROM AUTHOR]

Transdermal drug delivery has been an increasingly studied alternative drug administration route owing to the large surface area of the skin, enabling ease of access and application. Among the various transdermal drug delivery technologies that have been developed so far, microarray patches (MAPs) incorporating microneedle technology (MN) have garnered much attention. MAPs can easily penetrate the stratum corneum, facilitating the delivery of desired substances directly into the skin, exhibiting a higher delivery efficiency compared to alternative transdermal drug delivery approaches. The effectiveness of MAPs in delivering therapeutics is affected by a multitude of factors, one of which is the selection of materials employed in their fabrication. Among various materials that have been used to fabricate MAPs, synthetic biodegradable polymers such as poly(lactic‐co‐glycolic acid) (PLGA) and polylactic acid (PLA) have been exploited for sustained and controlled release with excellent biocompatibility. PLGA and PLA can be used to construct the entire needle shaft or drug‐loaded microparticles which are then incorporated into needle layer. The combination of MN technology in conjunction with biodegradable polymers has revolutionized sustained and controlled transdermal delivery of small and large molecules. [ABSTRACT FROM AUTHOR]

Transdermal drug delivery systems have received a lot of attention due to their noninvasive nature and possible advantages over standard drug administration methods. Because transdermal administration systems skip the gastrointestinal tract and hence avoid hepatic first pass metabolism, also the chance of adverse effects such as liver malfunction and gastrointestinal tract discomfort is low. This comprehensive review explores the various aspects of polymeric advancements in transdermal drug delivery, encompassing their roles as matrix and microreservoir formers, microneedles, pressure sensitive adhesives, rate controlling membranes, and many other components. The article emphasizes the importance of biocompatibility, chemical compatibility, and stability of polymers within the transdermal delivery system. Furthermore, it delves into the recent advancements in synthetic and natural polymer‐based transdermal drug delivery systems. Thus, a comprehensive search strategy is conducted in electronic databases such as PubMed, Scopus, and Web of Science to write this review paper. The scope of this investigation involves an in‐depth study of the various polymeric materials used, their formulations, and the mechanisms that support their efficacy in delivering medications over the skin barrier. Additionally, it explores the challenges associated with stability and safety concerns, while highlighting novel approaches to overcome these problems. Furthermore, the review discusses the biocompatibility of polymeric materials, crucial for ensuring minimal adverse effects and maximum therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Microneedles (MNs) are minimally invasive transdermal drug delivery systems capable of penetrating the stratum corneum to overcome the barrier properties. The primary objective of this research was to prepare dissolving microneedle patches (DMNP) loaded with quetiapine (QTP). DMNP were fabricated employing the solvent casting technique, utilizing various polymer feed ratios including polyvinyl alcohol (PVA), polyvinylpyrrolidone K30 (PVP-K30), and polylactide-co-glycolide (PLGA) polymers. The loaded DMNP with QTP underwent a comprehensive characterization process encompassing assessments for compatibility, thickness, insertion potential, morphology, thermal behavior, X-ray diffraction, ex-vivo permeation, skin irritation, and histopathological changes. FTIR studies confirmed the compatibility of QTP with the microneedle patch composites. The thickness of the drug-loaded DMNP ranged from 0.67 mm to 0.97 mm. These microneedles exhibited an impressive penetration depth of 480 μm, with over 80% of the needles maintaining their original shape after piercing Parafilm-M. SEM analysis of the optimized DMNP-2 revealed the formation of sharp-tipped and uniformly surfaced needles, measuring 570 μm in length. Remarkably, the microneedles did not elicit any signs of irritation upon application of the prepared DMNP. The DMNP-2 showcased an impressive cumulative ex-vivo permeation of QTP, reaching 17.82 µg/cm2/hr. Additionally, histopathological assessment of vital organs in rabbits attested to the safety profile of the formulated microneedle patches. In conclusion, the developed microneedle patch represents a promising strategy for enhancing the transdermal delivery of QTP. This innovative approach has the potential to increase patient compliance, offering a more efficient and patient-friendly method of administering QTP. [ABSTRACT FROM AUTHOR]

We developed a sustained-release transdermal drug delivery system (TDDS) containing simvastatin (SIM) and captopril (CAP) to treat hypertension and hyperlipidemia and overcome treatment drawbacks, including significant liver first-pass effects, low bioavailability, and the short half-life of SIM and CAP oral tablets. We used a transdermal diffusion meter to preselect the formula of the SIM-CAP TDDS. Based on in vitro permeation experiments, we optimized the formula of the SIM-CAP TDDS to include 24% SIM, 24% CAP, 34% polyvinyl alcohol (PVA), 16% oleic acid (OA)–azone, and 2% polyacrylic acid resin II. We evaluated the optimized SIM-CAP TDDS formula by its appearance, stability, stickiness, drug content, in vivo pharmacokinetics, and skin irritation tests. The results indicated that the patch had good stability and stickiness. The SIM and CAP contents were 5.02 ± 0.41 mg/cm2 in the 1 cm2 SIM-CAP TDDS. The pharmacokinetic results indicated that the system continuously released SIM and CAP for 24 h and significantly enhanced their bioavailability, with a higher area under the curve. The SIM-CAP TDDS exhibits a sustained-release effect with good characteristics and pharmacokinetics. And it is safe and has no irritating effects on the skin; therefore, it is an ideal formulation. [ABSTRACT FROM AUTHOR]

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%). [ABSTRACT FROM AUTHOR]

Our comprehensive review plunges into the cutting-edge advancements of polymeric microneedle drug delivery systems, underscoring their transformative potential in the realm of transdermal drug administration. Our scrutiny centers on the substrate materials pivotal for microneedle construction and the core properties that dictate their efficacy. We delve into the distinctive interplay between microneedles and dermal layers, underscoring the mechanisms by which this synergy enhances drug absorption and precision targeting. Moreover, we examine the acupoint–target organ–ganglion nexus, an innovative strategy that steers drug concentration to specific targets, offering a paradigm for precision medicine. A thorough analysis of the clinical applications of polymeric microneedle systems is presented, highlighting their adaptability and impact across a spectrum of therapeutic domains. This review also accentuates the systems' promise to bolster patient compliance, attributed to their minimally invasive and painless mode of drug delivery. We present forward-looking strategies aimed at optimizing stimulation sites to amplify therapeutic benefits. The anticipation is set for the introduction of superior biocompatible materials with advanced mechanical properties, customizing microneedles to cater to specialized clinical demands. In parallel, we deliberate on safety strategies aimed at boosting drug loading capacities and solidifying the efficacy of microneedle-based therapeutics. In summation, this review accentuates the pivotal role of polymeric microneedle technology in contemporary healthcare, charting a course for future investigative endeavors and developmental strides within this burgeoning field. [ABSTRACT FROM AUTHOR]

Purpose: Additive manufacturing (AM), also known as three-dimensional (3D) printing technology, has been used in the health-care industry for over two decades. It is in high demand in the health-care industry due to its strength to manufacture custom-designed and personalized 3D constructs. Recently, AM technologies are being explored to develop personalized drug delivery systems, such as personalized oral dosages, implants and others due to their potential to design and develop systems with complex geometry and programmed controlled release profile. Furthermore, in 2015, the US Food and Drug Administration approved the first AM medication, Spritam® (Apprecia Pharmaceuticals) which has led to tremendous interest in exploring this technology as a bespoke solution for patient-specific drug delivery systems. The purpose of this study is to provide a comprehensive overview of AM technologies applied to the development of personalized drug delivery systems, including an analysis of the commercial status of AM based drugs and delivery devices. Design/methodology/approach: This review paper provides a detailed understanding of how AM technologies are used to develop personalized drug delivery systems. Different AM technologies and how these technologies can be chosen for a specific drug delivery system are discussed. Different types of materials used to manufacture personalized drug delivery systems are also discussed here. Furthermore, recent preclinical and clinical trials are discussed. The challenges and future perceptions of personalized medicine and the clinical use of these systems are also discussed. Findings: Substantial works are ongoing to develop personalized medicine using AM technologies. Understanding the regulatory requirements is needed to establish this area as a point-of-care solution for patients. Furthermore, scientists, engineers and regulatory agencies need to work closely to successfully translate the research efforts to clinics. Originality/value: This review paper highlights the recent efforts of AM-based technologies in the field of personalized drug delivery systems with an insight into the possible future direction. [ABSTRACT FROM AUTHOR]

The human skin is a readily accessibl esurface for drug delivery. Skin of an average adult body covers a surface of approximately 2m2 and receives about one-third of the blood circulating through the body. Over the past decades, developing controlled drug delivery as become increasingly important in the pharmaceutical industry. The human skin surface is known to contain, on anaverage, 10-70 hair follicles and 200-250 sweat ducts on every square centimeters of the skin area. It is one of the most readily accessibl eorgans of the human body. There is considerable interest in the skin as a site of drug application both for local and systemic effect. However, thes kin, in particular the stratum corneum, poses a formid able barrier drug penetration there by limiting topical and Transdermal bioavailability. Skin penetration enhancement techniques have been devel oped to improve bioavailability and increase the range of drugs for which topical and Transdermal delivery syste(NDDS). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Recently, drug release applications through the skin have become very popular. One of the most remarkable of these drug release applications is transdermal drug release systems, which are drug release methods that allow the active substance to pass into the systemic circulation through the skin or artificial membranes. In this study, the optimization conditions required for the release and permeation tests of a gel drug containing the active substance thiocolchicoside were comparatively investigated using synthetic membranes without human or animal skin. For this purpose, the permeability of the gel drug in gel form and the active ingredient thiocolchicoside was carried out using Franz Diffusion Cell. As a result of the investigations, it was observed that the best synthetic membrane for the permeability of thiocolchicoside in the Franz Diffusion Cell was the Supor membrane. In addition, the method's relative standard deviation values, detection, and quantification limits were determined, and permeation studies were carried out. In this study, the correlation coefficient was found to be 0.9992, and the limits of detection and quantification were 0.026 and 0.078 µg/L. In this way, the sensitivity and reliability of the validation study were determined. [ABSTRACT FROM AUTHOR]

Compared to other forms of drug administration, the use of Transdermal Drug Delivery Systems (TDDSs) offers significant advantages, including uniform drug release profiles that contribute to lower side effects and higher tolerability, avoidance of direct exposure to the gastrointestinal tract, better patient compliance due to their non-invasive means of application and others. Mesoporous silica membranes are of particular interest in this regard, due to their chemical stability and their tunable porous system, with adjustable pore sizes, pore volumes and surface chemistries. While this allows for fine-tuning and, thus, the development of optimized TDDSs with high loading capacities and the desired release profile of a given drug, its systemic availability also relies on skin penetration. In this paper, using a TDDS based on mesoporous silica membranes in Franz cell experiments on porcine skin, we demonstrate surprisingly substantial drug loss during skin penetration. Drug passage through porcine skin was found to be dependent on the age and pre-treatment of the skin. pH and temperature were major determinants of drug recovery rates as well, indicating drug loss in the skin by enzymatic metabolization. Regarding the TDDS, higher loading obtained by SO3H surface modification of the mesoporous silica membranes reduced drug loss. Still, high loss rates in the skin were determined for different drugs, including anastrozole, xylazine and imiquimod. We conclude that, beyond the fine-tuned drug release profiles from the mesoporous silica membrane TDDS, remarkably high drug loss in the skin is a major issue for achieving desired skin penetration and, thus, the systemic availability of drugs. This also poses critical requirements for defining an optimal TDDS based on mesoporous silica membranes. [ABSTRACT FROM AUTHOR]

The stratum corneum layer of skin poses a major barrier for transdermal drug delivery. Recently, nanocarriers and microneedles fabricated from renewable polymers have emerged as promising platforms to enhance permeation across this barrier. This letter highlights recent progress in using biocompatible nanocarriers and microneedle arrays to improve transdermal drug delivery. [ABSTRACT FROM AUTHOR]

Controllable and long‐term release remains a great challenge in current drug delivery systems. Benefiting from their efficient drug loading and painless administration, microneedles (MNs) have emerged as a promising platform for transdermal drug delivery, while they often fail to achieve long‐term tissue adhesion and controllable extended drug release. Here, 3D printing of an innovative MN patch is presented with succulent‐inspired responsive microstructures and light‐controllable long‐term release capability. The MN exhibits a reversible shrink‐swell volume change behavior in response to surrounding humidity, which enables sufficient mechanical strength for skin penetration under the shrinkage conditions and efficient long‐term adhesion when swollen in skin tissues. Moreover, the MN patch introduces a controllable long‐term drug release system, achieved through the integration of thiolated heparin (Hep‐SH) for sustained growth factor release and graphene oxide (GO) nanosheets for controlled drug release via near infrared (NIR) laser irradiation. The MN patches with growth factor loading have good biocompatibility and can promote the proliferation, migration, and proangiogenesis of endothelial cells is further demonstrated. Thus, it is believed that such flexible MN patches can be promising candidates for controllable long‐term transdermal drug delivery as well as other related tissue engineering applications. [ABSTRACT FROM AUTHOR]

There is a global trend of increasing antibiotic resistance to Gram‐negative bacteria and the medical research community is looking for alternative antibiotics. Antibiotics such as polymyxin B (PMB) show excellent efficacy and low resistance rates against Gram‐negative bacteria. The topical administration of PMB, however, has clinical limitations such as minimal residence time, making it difficult for its use to treat skin infections. Here, we present porous silicon microneedle (pSi MN) patches to deliver PMB to the skin. pSi MN patches are fabricated by, first, generating the projections by dry Si etching techniques, followed by an electrochemical etching to create porous layers around the MNs. After loading PMB into the porous layer, the antibacterial activity of pSi MNs is determined by measuring the inhibition zone of Gram‐negative Escherichia coli. Next, PMB is efficiently delivered into the epidermal layer of ex vivo skin models, as confirmed by chemical mapping using matrix‐assisted laser desorption/ionization mass spectrometry imaging (MALDI‐MSI). The results demonstrate that pSi MN patches are an efficient and versatile tool for the transdermal delivery of PMB with maintained bioactivity and antimicrobial efficacy, thus expanding the possibilities of current transdermal drug delivery systems. [ABSTRACT FROM AUTHOR]

Nowadays, transdermal drug delivery system (TDDS) has been developed continuously because it solves the problem of drug level inconsistencies in the blood and prevents the drug from being destroyed in the digestive tract. However, the limitations of TDDS are the low release rate of the patch and difficult penetration of the drug to the skin. Therefore, this research aims to study drug release behavior of aspirin with and without applied electrical potential for controlled drug release from the pullulan hydrogel patch using sodium trimetaphosphate and citric acid at various concentrations as the crosslinker. The pullulan hydrogel patches prepared by the solvent casting method were studied the release behavior by using a modified franz diffusion cell with containing pH 5.5 and 7.4 buffer solution at 37 ◦C for 2 h. The amount of drug release was compared with various electrical potentials as 0, 0.5, 1, 3, and 5 V. The aspirin release behavior from pullulan hydrogel was a Non-Fickian mechanism meaning that the aspirin was released via concentration gradient combined with swelling behavior of drug matrix. The amount of drug release and releasing rate was decreased with increasing the crosslinking ratio because of the lower the swelling behavior of matrix. In addition, the applied electrical stimulation enhanced the amount of drug release and releasing rate. The maximum release of aspirin is approximately 25% within 9 min from the hydrogel patch using sodium trimetaphosphate as a crosslinker and a 5 V which is higher than that of 0 V as 16% within 12 min. [ABSTRACT FROM AUTHOR]

The present study proposes an innovative transdermal drug delivery system using ferrocene-incorporated fibers to enhance the bioavailability and therapeutic efficacy of ascorbyl tetraisopalmitate. Using electrospinning technology, the authors created ferrocene polymer fibers capable of highly efficient drug encapsulation and controlled release in response to reactive oxygen species commonly found in wound sites. The approach improves upon previous methods significantly by offering higher drug loading capacities and sustained release, directly targeting diseased cells. The results confirm the potential of ferrocene fibers for localized drug delivery, potentially reducing side effects and increasing patient convenience. The method could facilitate the application of bioactive compounds in medical textiles and targeted therapy. [ABSTRACT FROM AUTHOR]

A pioneering approach in the domain of transdermal drug delivery systems (TDDS) is introduced by using microneedles (MNs) fabricated from an amorphous solid dispersion comprising only a model drug and an amphiphilic block copolymer to form a drug nanoformulation upon MN dissolution. To maximize drug loading and ensure consistent release, a minimalist formulation that achieves 40 wt% drug loading, which is a significant improvement over existing methods, is developed. Using scanning electron microscopy, the morphology of MNs is examined across a spectrum of drug loading ratios, demonstrating the consistency in structure and integrity. Mechanical testing confirms the MNs' proficiency in effective skin penetration. A comparative study on the formation of polymeric micelles underscores the innovative concept of a “nano‐in‐micro drug delivery system”. The results demonstrate that MNs manufactured from an amorphous solid dispersion of drug and amphiphilic block copolymer with ultra‐high loading enhance the availability and release dynamics of hydrophobic drugs, positioning them as a tool for enhancing TDDS. This study sets a new benchmark in the utilization of polymer‐drug nanoformulations for transdermal applications and underscores the capacity for high drug loading and the creation of adaptable drug delivery mechanisms for the studied amphiphilic block copolymer. [ABSTRACT FROM AUTHOR]

Targeted drug delivery systems are employed to administer pharmaceutical medication, facilitating the precise delivery of drugs to specific diseased areas. Several drug delivery systems utilise carriers such as antibodies, transdermal patches, biodegradable polymers, Nanoparticles (NPs), liposomes, niosomes, and microspheres. Niosomes, on the other hand, represent a promising and innovative category of vesicular systems. Non-ionic surfactant vesicles commonly referred to as niosomes, have garnered significant attention within the pharmaceutical industry due to their remarkable capacity to versatility in encapsulation for both hydrophilic and hydrophobic drugs. Recent studies have demonstrated the potential of these vesicles to enhance the bioavailability of drugs, making them a promising strategy for delivering various therapeutic agents such as gene materials, protein therapeutics, and chemical pharmaceuticals. This approach offers minimal toxicity and desirable targeting effectiveness. Niosomes has non-immunogenic properties and can be designed as a controlled release drug that payload slowly and steadily, reducing the risk of side effects and improving therapeutic efficacy. Niosomes are substantially more stable during the preparation and storage procedure than liposomes. Liposomes are generally less stable than niosomes due to their susceptibility to enzymatic degradation and leakage of encapsulated materials. The desired pharmacokinetics property can be attained through the optimization of constituents or surface modifications. This novel method of distribution is also facile to establish and expand while maintaining cost-effective manufacturing expenses. This review article elucidates the fundamentals of niosomes as non-ionic surfactant vesicles, including their structure and components, as well as various formulation methods. Additionally, the article explores the diverse applications of niosomal in analgesics. [ABSTRACT FROM AUTHOR]

The transdermal drug delivery system (TDDS) was created with the main goals of achieving extended pharmaceutical release, increasing bioavailability, and enhancing patient adherence. The matrix dispersion transdermal patch works by dispersing the drug and polymers in a solvent, which is then evaporated to leave a homogenous drug-polymer matrix. The goals of the present study were on designing and formulating TDDS for tirzepatide and afterwards assessing their in vitro performance characteristics. In diabetes mellitus, the pancreas either produces inadequate amounts of insulin or the body is unable to properly use the insulin that is generated. More than 415 million people worldwide have diabetes, and it is anticipated that by 2040, that number would reach 642 million. By 2030, diabetes will surpass heart disease as the seventh largest cause of death, according to the WHO. [ABSTRACT FROM AUTHOR]

A transdermal drug delivery system (TDDS) is characterized by the application of medications onto the skin's surface to deliver drugs at a controlled and predefined rate through the skin. Spanlastics, an elastic nanovesicle capable of transporting various pharmacological substances, shows promise as a drug delivery carrier. It offers numerous advantages over traditional vesicular systems applied topically, including enhanced stability, flexibility in penetration, and improved targeting capabilities. This study aims to develop meloxicam (MX)-loaded spanlastics gel as skin delivery carriers and to look into the effects of formulation factors like Tween80, Brij 35, and carbopol concentration on the properties of spanlastics gel, like pH, drug content, extrudability, spreadability diameter, viscosity, and release profiles in addition to Ex vivo skin permeation for optimal formula. The optimal formula of spanlastics gel (GF1) shows acceptable pH (6.2±0.14), excellent extrudability( 92%), drug content (97.1±0.14), spreadability diameter (cm) (10.8±0.28), sustained release 70.7±0.57% for six hours and the steady-state flux of meloxicam through rat skin was increased 83.52- fold as a result of spanlastics in comparison to the plain gel. The vesicles produced in this investigation could potentially interact with or merge with the stratum corneum as a result of their elasticity, which may also be the mechanism that increases the penetration into the skin. According to our findings, dermal delivery vehicles for MX may be provided via spanlastics gel. [ABSTRACT FROM AUTHOR]

AbstractMicroneedles, as a new efficient and safe transdermal drug delivery technology, has a wide range of applications in drug delivery, vaccination, medical cosmetology, and diagnostics. The degree of microneedles penetration into the skin determines the reliability of the delivery dose, but its evaluation is not yet well-established, which is one of the major constraints in the commercialization of microneedles. In this paper, a novel visual simulated skin model was developed with reference to the physical properties of real skin. The simulated skin model was well-designed and its prescription was optimized to make the thickness, hardness, elasticity, and other parameters close to those of real skin. It not only meets the need to assess the degree of insertion of microneedles but also provides a visual observation of the insertion state of microneedles. [ABSTRACT FROM AUTHOR]

Sonophoresis is the most approachable mode of transdermal drug delivery system, wherein low‐frequency sonophoresis penetrates the drug molecules into the skin. It is an alternative method for an oral system of drug delivery and hypodermal injections. The cavitation effect is thought to be the main mechanism used in sonophoresis. The cavitation process involves forming a gaseous bubble and its rupture, induced in the coupled medium. Other mechanisms used are thermal effects, convectional effects, and mechanical effects. It mainly applies to transporting hydrophilic drugs, macromolecules, gene delivery, and vaccine delivery. It is also used in carrier‐mediated delivery in the form of micelles, liposomes, and dendrimers. Some synergistic effects of sonophoresis, along with some permeation enhancers, such as chemical enhancers, iontophoresis, electroporation, and microneedles, increased the effectiveness of drug penetration. Sonophoresis‐mediated ocular drug delivery, nail drug delivery, gene delivery to the brain, sports medicine, and sonothrombolysis are also widely used. In conclusion, while sonophoresis offers promising applications in diverse fields, further research is essential to comprehensively elucidate the biophysical mechanisms governing ultrasound‐tissue interactions. Addressing these gaps in understanding will enable the refinement and optimization of sonophoresis‐based therapeutic strategies for enhanced clinical efficacy. [ABSTRACT FROM AUTHOR]

Objective: The objective of the present study was to enhance the bioavailability of cannabidiol (CBD) using 3D Digital Light Processing (DLP)-printed microneedle (MN) transdermal drug delivery system. Methods: CBD MN patch was fabricated and optimized using 3D DLP printing using CBD (8% w/v), Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) (0.49% w/v), distilled water (20% w/v), and poly (ethylene glycol) dimethacrylate 550 (PEGDAMA 550) (up to 100% w/v). CBD MNs were characterized for their morphology, mechanical strength, in vitro release study, ex vivo permeation study, and in vivo pharmacokinetic (PK) profile. Key findings: Microscopic images showed that sharp CBD MNs with a height of ~800 μm, base diameter of ~250 μm, and tip with a radius of curvature (RoC) of ~15 μm were successfully printed using optimized printing parameters. Mechanical strength studies showed no significant deformation in the morphology of CBD MNs even after applying 0.5N/needle force. Ex vivo permeation study showed significant (P <.0001) permeation of CBD in the receiving media as compared to CBD patch (control). In vivo PK study showed significantly (P <.05) enhanced bioavailability in the case of CBD MN patch as compared to CBD subcutaneous inj. (control). Conclusion: Overall, systemic absorption of CBD was significantly enhanced using 3D-printed MN drug delivery system. Graphical Abstract [ABSTRACT FROM AUTHOR]

In transdermal drug delivery system (TDDS) patches, achieving prolonged adhesion, high drug loading, and rapid drug release simultaneously presented a significant challenge. In this study, a PHT-SP-Cu2+ adhesive was synthesized using polyethylene glycol (PEG), hexamethylene diisocyanate (HDI), trimethylolpropane (TMP), and silk protein (SP) as functional monomers which were combined with Cu2+ to improve the adhesion, drug loading, and drug release of the patch. The structure of the adhesion chains and the formation of Cu2+-p-π conjugated network in PHT-SP-Cu2+ were characterized and elucidated using different characterization methods including FT-IR, 13C NMR, XPS, SEM imaging and thermodynamic evaluation. The formulation of pressure-sensitive adhesive (PSA) was optimized through comprehensive research on adhesion, mechanics, rheology, and surface energy. The formulation of 3 wt.% SP and 3 wt.% Cu2+ provided superior adhesion properties compared to commercial standards. Subsequently, the peel strength of PHT-SP-Cu2+ was 7.6 times higher than that of the commercially available adhesive DURO-TAK® 87–4098 in the porcine skin peel test. The adhesion test on human skin confirmed that PHT-SP-Cu2+ could adhere to the human body for more than six days. Moreover, the drug loading, in vitro release test and skin permeation test were investigated using ketoprofen as a model drug, and the results showed that PHT-SP-Cu2+ had the efficacy of improving drug compatibility, promoting drug release and enhancing skin permeation as a TDDS. Among them, the drug loading of PHT-SP-Cu2+ was increased by 6.25-fold compared with PHT, and in the in vivo pharmacokinetic analysis, the AUC was similarly increased by 19.22-fold. The mechanism of α-helix facilitated drug release was demonstrated by Flori-Hawkins interaction parameters, molecular dynamics simulations and FT-IR. Biosafety evaluations highlighted the superior skin cytocompatibility and safety of PHT-SP-Cu2+ for transdermal applications. These results would contribute to the development of TDDS patch adhesives with outstanding adhesion, drug loading and release efficiency. A new adhesive, PHT-SP-Cu2+, was created for transdermal drug delivery patches. Polyethylene glycol, hexamethylene diisocyanate, trimethylolpropane, silk protein, and Cu2+ were used in synthesis. Characterization techniques confirmed the structure and Cu2+-p-π conjugated networks. Optimal formulation included 3 wt.% SP and 3 wt.% Cu2+, exhibiting superior adhesion. PHT-SP-Cu2+ showed 7.6 times higher peel strength than DURO-TAK® 87–4098 on porcine skin and adhered to human skin for over six days. It demonstrated a 6.25-fold increase in drug loading compared to PHT, with 19.22-fold higher AUC in vivo studies. α-helix facilitated drug release, proven by various analyses. PHT-SP-Cu2+ showed excellent cytocompatibility and safety for transdermal applications. This study contributes to developing efficient TDDS patches. [Display omitted] [ABSTRACT FROM AUTHOR]

In recent times, the demand for innovative, insignificantly invasive diagnostic and therapeutic biomedical tools has reached enhanced attention. Rapid Diagnostic Tests (RDTs) for diagnosis, which are non-invasive, inexpensive, simple, and deliver results accurately in less than 20 minutes, have heightened the accessibility to parasite-based analysis globally. Microneedle (MN) arrays are a fast-developing and promising technology for drug delivery and extraction of Interstitial fluid (ISF) employed for numerous diagnostic and clinical therapies. This review gives a broad overview of the characteristics and history of Microneedles (MNs) patches together with their applications in drug delivery and transdermal rapid diagnostic purposes, classifications, and categories based on the design of fabrication from previous works of literature spanning the period 2018-2023. Utilizing PubMed, Scopus, Google Scholar, and Wiley online library search engines, an online search for scientific publications published between 2018 and 2023 was conducted using the keywords "microneedle patch" and "rapid diagnostic tests." 175 articles in all were found when the search terms were used. The acquired results were then narrowed to 64 citations in this review by applying the inclusion principle. Pictorial and tabular representations highlight the various features of Microneedle patches used in interstitial fluid testing and extraction that have been documented experimentally, including numerous applications of Microneedle patches, showing their dimensions, applications, fabrication methods, and findings made. Finally, research on bio-microneedles and bio-inspired MN are reviewed. The research findings indicate that dissolving microneedles has become increasingly popular since they have several benefits over other microneedles. It is among the most well-known microneedles, and since it degrades naturally, it is a superior option for diagnosis and long-term treatment. [ABSTRACT FROM AUTHOR]

BACKGROUND: Gold nanoparticles are of great significance in the development of multifunctional transdermal drug delivery systems. Smaller gold nanoparticles can penetrate the dermis through the intercellular pathway, but are limited to their easy agglomeration and colloidal morphology, which makes it difficult to exert effects on low delivery efficiency. OBJECTIVE: To develop an ultrasound-optimized hydrogel delivery system by combining phase change nanodroplets with bio-adhesive hydrogel for percutaneous delivery of gold nanoparticles. METHODS: The ultrasound-responsive nanodroplets loaded with gold nanoparticles were prepared by the emulsion solvent evaporation method and loaded into the polydopamine-modified methylacryloyl gelatin hydrogel to prepare a composite hydrogel scaffold. The structure and chemical composition of the ultrasound-responsive nanogold carrier were characterized. The microstructure, porosity, permeability, rheology, in vitro hemostasis, and antibacterial properties of the composite hydrogel were characterized. The cell compatibility of the hydrogel scaffold was evaluated by live/dead staining, and the optimization effects of low-intensity pulsed ultrasound on the permeability, porosity, and mechanical properties of hydrogel were evaluated. RESULTS AND CONCLUSION: (1) Transmission electron microscopy and ultraviolet-visible spectroscopy proved the successful construction of nanogold carriers. The particle size and potential results demonstrated that the synthesized nanoscaled ultrasonic responsive carrier had good stability. (2) Live/dead cell staining proved that the prepared composite hydrogel scaffold had certain biocompatibility. (3) Scanning electron microscopy exhibited that the prepared composite hydrogel scaffold had a porous network structure, and numerous pores of about 2 μm appeared inside the macropores after the addition of nanodroplets and ultrasonic irradiation. The permeability experiment displayed that low-intensity pulsed ultrasound could optimize the porosity and permeability of hydrogel materials. The hemostatic performance of the composite hydrogel scaffold was better than that of the hemostatic sponge and polydopamine@ methylacrylylated gelatin hydrogel scaffold. Under the irradiation of low-intensity pulsed ultrasound, the composite hydrogel scaffolds had good antioxidant effects and antibacterial properties. (4) Thermal imaging results manifested that gold nanoparticles were encapsulated in ultrasound-responsive nanobubbles, and more uniform dispersion could be obtained under ultrasonic excitation. (5) The results of the mechanical property test demonstrated that the storage modulus of the hydrogel increased before and after loading gold nanoparticles-nanodroplets, which showed stronger mechanical properties. The elongation at break was 122%, and the ductility was better than that without gold nanoparticles-nanodroplets (P < 0.05). (6) These findings indicate that the composite hydrogel scaffold has good biocompatibility, antibacterial property, oxidation resistance, and hemostatic effect. [ABSTRACT FROM AUTHOR]

Franz diffusion cell was primarily used to evaluate the permeability and stability of formulations such as topical (gels and creams) and transdermal (lipid nanoparticle formulations). Diffusion cell is a straightforward assay that can reliably measure the in-vitro and ex-vivo drug release from topical preparations such as creams, ointments, liposomes formulations, and gels. It offered crucial critical perspectives on skin, drug, and formulation relationships. In addition, it is also employed for toxicity testing and quality control. Currently, many medications are available in the market, administered through transdermal routes. To treat various skin conditions, medical professionals use a wide range of methods aimed at increasing the skin's permeability and drug absorption. The biggest challenge with transdermal drug delivery system is determining the amount of medication penetrating the skin. Today, there is a lot of research into creating new dermal dosage forms for pharmaceuticals. In this review, the authors discuss various evaluation methods to determine the amount of drug penetrating the skin. With their strengths and weaknesses, these models and assessment methods provide a valuable framework for investigating the dermato-pharmacokinetics of different transdermal formulations. The assessment techniques aid in assessing molecules that cause skin irritation by shedding light on the molecular mechanisms by which they penetrate the skin. These assessment tools and models provide a novel strategy for creating topical medicinal formulations for various skin infection disorders. The present review explores Franz diffusion cell application, its implication in pharmaceutical research, and the regulation related to pharmacopeia. [ABSTRACT FROM AUTHOR]

DMSO-inspired polymer is frequently applied in advanced biomedical aspects due to its highly hydrophilic, excellent biocompatibility, and negligible cytotoxicity nature. Herein, our study aimed for the first time to synthesize electrospun poly((2-methylsulfinyl)ethyl acrylate-co-acrylic acid) (PMSEA-AA) nanofibers as wound dressing materials. PAA was initially grafted through a steglich esterification reaction to obtain poly(2-(methylthio)ethyl acrylate-co-acrylic acid) copolymer (PMTEA-AA). Subsequently, the obtained copolymer was further oxidized and exposed to electrospinning to give PMSEA-AA nanofiber-containing sulfoxide groups. The chemical structure of as-obtained polymers was carefully confirmed by FTIR, UV–vis, 1H-NMR, TGA, DSC, and GPC. Further, PMSEA-AA nanofibers were observed with remarkable mechanical, hydrophilic, cell viability, and antibacterial behaviors. The tensile strength and elongation at a break for PMSEA-AA nanofibers were recorded as 9 MPa and 30%, which are higher compared to PAA fibers (6.33, 20%). The cell growth of PMTEA-AA nanofiber was considerably increased concerning pure PAA nanofiber approving the nontoxic capability due to the hydrophobicity nature and high surface area that can lead to effective contact with the cancer cells. Also, PMSEA-AA nanofiber could achieve superior bacterial inhibition zones of 12 and 9 mm for S. aureus and E. coli, respectively, compared to PAA. PMSEA-AA nanofibers could discover biomedical and pharmaceutical applications for wound healing materials, tissue engineering, and transdermal drug delivery system for skin and oral. [ABSTRACT FROM AUTHOR]

Poor skin adhesion and mechanical properties are common problems of pressure-sensitive adhesive (PSA) in transdermal drug delivery system (TDDS). Its poor water compatibility also causes the patch to fall off after sweating or soaking in the application site. To solve this problem, poly (2-Ethylhexyl acrylate- co - N -Vinyl-2-pyrrolidone- co - N -(2-Hydroxyethyl)acrylamide) (PENH), a cross-linked pyrrolidone polyacrylate PSA, was designed to improve the adhesion and water resistance of PSA through electrostatic force and hydrogen bonding system. The structure of PENH was characterized by 1H NMR, FTIR, DSC, and other methods. The mechanism was studied by FTIR, rheological test, and molecular simulation. The results showed that the PENH patch could adhere to human skin for more than 10 days without cold flow, and it could still adhere after sweating or water contact. In contrast, the commercial PSA Duro-Tak® 87-4098 and Duro-Tak® 87-2852 fell off completely on the 3rd and 6th day, respectively, and Duro-Tak® 87-2510 showed a significant dark ring on the second day. Mechanism studies have shown that the hydrogen bond formed by 2-ethylhexyl acrylate (2-EHA), N-vinyl-2-pyrrolidinone (NVP), and N -(2-Hydroxyethyl)acrylamide (HEAA) enhances cohesion, the interaction with skin improves skin adhesion, and the electrostatic interaction with water or drug molecules enhances the ability of water absorption and drug loading. Due to the synergistic effect of hydrogen bonds and electrostatic force, PENH can maintain high cohesion after drug loading or water absorption. PENH provides a choice for the development of water-compatible patches with long-lasting adhesion. Based on the synergistic effect of hydrogen bonding and electrostatic force, a hydrogen-bonded, cross-linked pyrrolidone acrylate pressure-sensitive adhesive for transdermal drug delivery was designed and synthesized, which has high adhesion and cohesive strength and is non-irritating to the skin. The patch can be applied on the skin surface continuously for more than 10 days without the phenomenon of "dark ring", and the patch can remain adherent after the patient sweats or bathes. This provides a good strategy for choosing a matrix for patches that require prolonged administration. [Display omitted] [ABSTRACT FROM AUTHOR]

In this study, dissolving microneedles (MNs) using polyvinyl alcohol (PVA) and poly (1-vinylpyrrolidone-co-vinyl acetate) (P(VP-co-VA)) as matrix materials were developed for transdermal delivery of rizatriptan benzoate (RB) for acute migraine treatment. In-vitro permeation studies were conducted to assess the feasibility of the as-fabricated dissolving MNs to release RB. Drug skin penetration were tested by Franz diffusion cells, showing an increase of the transdermal flux compared to passive diffusion due to the as-fabricated dissolving MNs having a sufficient mechanical strength to penetrate the skin and form microchannels. The pharmacological study in vivo showed that RB-loaded dissolving MNs significantly alleviated migraine-related response by up-regulating the level of 5-hydroxytryptamine (5-HT) and down-regulating the levels of calcitonin gene-related peptide (CGRP) and substance P (SP). In conclusion, the RB-loaded dissolving MNs have advantages of safety, convenience, and high efficacy over conventional administrations, laying a foundation for the transdermal drug delivery system treatment for acute migraine. [ABSTRACT FROM AUTHOR]

Background: The growing popularity of transdermal patches is attributed to their advantageous characteristics, including the absence of gastric-related problems, prolonged drug release, enhanced safety and stability, and the elimination of the need for punctures during systemic delivery. These features have prompted the exploration of novel techniques and innovations in transdermal delivery systems to optimize drug administration. Materials and Methods: To address the aforementioned advantages, researchers have focused on incorporating innovative approaches, with a particular emphasis on the utilization of nano-vesicular systems. The nano-vesicular system has gained favour due to its potential to significantly increase drug accumulation at the site of administration, its capacity to easily incorporate a wide range of medications, and its ability to minimize systemic drug absorption. This study undertook an examination of the attempts made in the development and implementation of transdermal nano-vesicular administration. Results: This study revealed the successful adoption and application of nano-vesicular systems in transdermal drug delivery. The results highlight the efficacy of this approach in enhancing drug accumulation at the administration site and its versatility in accommodating various medications. Additionally, the observed low systemic drug absorption further underscores the potential benefits of transdermal nano-vesicular administration. Conclusion: In conclusion, the study demonstrates the increasing significance of transdermal patches and the promising role played by nano-vesicular systems in addressing key challenges associated with systemic drug delivery. The successful examination of transdermal nano-vesicular administration by the authors emphasizes the advancements in this field and encourages further exploration of its potential applications in pharmaceutical delivery systems. [ABSTRACT FROM AUTHOR]

Background and Objectives: Doxorubicin hydrochloride (DOX-HCl), a potent and extensively utilized anticancer medication, faces limitations in skin penetration, resulting in confined effectiveness. Frequent administration leads to resistance at the site of application. This study aims to strike a balance between precision and selectivity to enhance DOX-HCl's permeation. The goal is to achieve non-invasive drug delivery that avoids issues linked with conventional therapies. This will be achieved through the utilization of patches loaded with transfersomes for drug delivery. Materials and Methods: Transferosomes were prepared through the rotary evaporation technique and optimized by Box-Behnken experimental design. The impact of phospholipid, cholesterol, and tween-80 on drug entrapment efficiency and particle size was assessed using analysis of variance. The resulting formulations underwent characterization involving particle size, zeta potential, transmission electron microscopy, and Fourier-transform infrared spectroscopy. In addition, drug entrapment efficiency, in vitro drug release patterns, ex vivo drug permeation profiles, and histopathological evaluations of the optimized formulations were conducted. Results: The particle size ranged from 53 to 168 nm, with drug entrapment efficiency ranging from 30.8 ± 0.06 to 87.90 ± 0.02%. The optimum formulation exhibited a zeta potential of -24.9 mV and achieved an approximately fourfold increase in permeation rate compared to a pure drug suspension. Histopathological studies of rat abdominal skin samples post-treatment with transferosomes patch indicate a moderate epidermal inflammation versus normal morphology for untreated skin. Conclusion: Utilizing transferosomes in transdermal drug delivery systems (TDDS) presents a promising strategy to address challenges associated with conventional therapies. By incorporating transferosomes into patches, this approach offers a multi-faceted solution to enhance non-invasive drug delivery. [ABSTRACT FROM AUTHOR]

Ionic liquids (ILs) have been proven to be an effective technology for enhancing drug transdermal absorption. However, due to the unique structural components of ILs, the design of efficient ILs and elucidation of action mechanisms remain to be explored. In this review, basic design principles of ideal ILs for transdermal drug delivery system (TDDS) are discussed considering melting point, skin permeability, and toxicity, which depend on the molar ratios, types, functional groups of ions and inter-ionic interactions. Secondly, the contributions of ILs to the development of TDDS through different roles are described: as novel skin penetration enhancers for enhancing transdermal absorption of drugs; as novel solvents for improving the solubility of drugs in carriers; as novel active pharmaceutical ingredients (API-ILs) for regulating skin permeability, solubility, release, and pharmacokinetic behaviors of drugs; and as novel polymers for the development of smart medical materials. Moreover, diverse action mechanisms, mainly including the interactions among ILs, drugs, polymers, and skin components, are summarized. Finally, future challenges related to ILs are discussed, including underlying quantitative structureactivity relationships, complex interaction forces between anions, drugs, polymers and skin microenvironment, long-term stability, and in vivo safety issues. In summary, this article will promote the development of TDDS based on ILs. [ABSTRACT FROM AUTHOR]

The goal of this study was to see if microemulsions might be used as a transdermal drug delivery system for acemetacin (ACM). Microemulsions containing isopropyl myristate, Tween 80, Transcutol HP, Labrafil M1944 CS, ethanol, and distilled water were used to create pseudo-ternary phase diagrams. In microemulsion systems, the ultimate concentration of ACM was 1% (w/w). Conductivity, droplet size, zeta potential, polydispersity index, viscosity, and pH were used to characterize the microemulsions. Furthermore, in vitro permeability investigations were carried out utilizing diffusion cells derived from the dorsal skin of mice. The results of characterization studies such as droplet size, polydispersity index, zeta potential, conductivity values of ideal formulation were found 9.107 ± 1.588 nm, 0.283 ± 0.062, −0.313 ± 0.006 mV, 0.018 ± 0.012 µS/cm, respectively. The penetration of ACM from ideal formulation was greater than the other developed formulations. The anti-inflammatory effect of ACM was evaluated in mice using the paw edema test. In addition, all test microemulsions had a significant analgesic effect in the hot plate and tail-flick tests as compared to the control. Finally, microemulsion formulations might be used to deliver ACM transdermally. [ABSTRACT FROM AUTHOR]

Over the past few decades, notable advancements have been made in the field of transdermal drug delivery systems (TDDSs), presenting a promising alternative to conventional oral drug administration. This comprehensive review aims to enhance understanding of this method by examining various transdermal techniques, the skin's role as a barrier to TDDS, factors affecting skin diffusion, and current challenges in TDDSs. The primary focus of this analysis centers on TDDSs utilizing hydrogels. A thorough exploration of hydrogel fundamentals, encompassing structure, properties, and synthesis, is provided to underscore the importance of hydrogels as carriers in transdermal drug delivery. The concluding section delves into strategies for hydrogel-based drug delivery, addressing challenges and exploring future directions. [ABSTRACT FROM AUTHOR]

Transdermal drug delivery refers to a drug delivery route that delivers drugs through the skin to produce local or systemic therapeutic effects. In this work, we propose a parallel valveless piezoelectric micropump integrated with hollow microneedle array, which can be used in flexible wearable transdermal drug delivery systems. The device consists of two valveless piezoelectric micropump, a hollow microneedle array and an electrical control module. The main structure of micropump and the hollow microneedle array are fabricated using 3D printing technology. The valveless piezoelectric micropump adopts a parallel dualpump structure with asynchronous drive, which achieves a full forward flow at the outlet and reduces the influence of backflow on the stability of the system. In addition, the parallel dual‐pump structure proposed in this work can be extended to a multimicropump parallel structure. We hope to fabricate small‐size micropump arrays on flexible substrates and integrate them into flexible wearable transdermal drug delivery systems. [ABSTRACT FROM AUTHOR]

Hypertrophic scar is a complex global disease, which can lead to remarkable functional impairment, pruritus, and pain. Treating local skin diseases needs a transdermal drug delivery system that can simultaneously promote cell and tissue penetration within the hypertrophic scar. Herein, a tissue and cell dual‐penetrating liposomal delivery platform consisting of arginine‐based dendritic lipopeptide mimicking the pivotal amino acid sequence in viral protein transduction domains and virion‐like nanostructure to enhance hypertrophic scar tissue deep penetration and cellular internalization is reported. This dendritic lipopeptide liposomal delivery platform can overcome corneum barriers to the punch on hypertrophic scar fibroblast membranes, as are natural viruses. It also can deeply deliver drugs to promote hypertrophic scar fibroblast apoptosis and collagen fiber remodeling within thickened dermis and epidermis, and finally remove the raised scars. [ABSTRACT FROM AUTHOR]

Transdermal drug delivery has gained significant attention as a non-invasive and convenient method for administering drugs. However, the stratum corneum, the outermost layer of the skin, poses a significant barrier to drug permeation. To overcome this challenge, vesicular carriers have emerged as promising systems for enhancing drug delivery through the skin. This review highlights recent advances in the development of vesicular carriers for transdermal drug delivery. Liposomes, niosomes, transfersomes, ethosomes, and solid lipid nanoparticles are among the commonly used vesicular carriers. These carriers offer advantages such as improved drug solubility, prolonged drug release, and enhanced drug stability. Additionally, they can encapsulate a wide range of drugs, including hydrophilic and lipophilic compounds. Various strategies have been employed to optimize vesicular carriers for transdermal drug delivery. These include modifying the vesicle composition, size, and surface charge to enhance skin penetration. The incorporation of penetration enhancers, such as surfactants, has also been explored to improve drug permeation across the skin. Furthermore, advancements in nanotechnology have led to the development of novel vesicular carriers, such as nanostructured lipid carriers and elastic liposomes. These carriers offer improved drug loading capacity, sustained release profiles, and enhanced skin penetration. Moreover, the use of vesicular carriers has shown promise in delivering a wide range of therapeutic agents, including small molecules, peptides, proteins, and genetic material. The ability to encapsulate and deliver these diverse drug entities opens new possibilities for transdermal drug delivery in various therapeutic areas. [ABSTRACT FROM AUTHOR]

The evaluation of drug percutaneous absorption plays a pivotal role in assessing the efficacy of dermal/transdermal drug delivery systems. Drug therapies rely on biomedical systems capable of precisely regulating drug dosage, controlling the rate of drug release, and mitigating the common side effects associated with many drug delivery formulations. Pluronics are being broadly used as amphiphilic excipients in many drug delivery systems due to their capacity to create supramolecular assemblies in water, exhibiting significant potential for sustained drug delivery. We herein report on the release kinetics of diclofenac sodium contained in novel biocompatible drug delivery systems consisting of aqueous solutions of Pluronic F68. The latter is tested as a release vehicle for percutaneous administration of diclofenac sodium. Its release from Pluronic F68 nanoassemblies in water was experimentally examined by means of a static Franz-type diffusion cell, equipped with a porous membrane simulating the skin absorption, and supported by rheology. Furthermore, the drug release process was modeled through a mass balance for the diclofenac sodium describing its diffusion in pseudostationary conditions through the porous membrane. [ABSTRACT FROM AUTHOR]

Transdermal drug delivery systems (TDDS) demand both high drug loading capacity and efficient delivery. In order to improve both simultaneously, this study aims to develop a novel rhamnose-induced pressure-sensitive adhesive (HPR) by dispersing the drug in the supramolecular helical structure. Ten model drugs, categorized as acidic and basic compounds, were chosen to understand the characteristics of the HPR and its inner mechanism. Notably, it enhanced drug loading by 1.41 to 5 times over commercially available pressure-sensitive adhesives Duro-Tak@ 87–4098 and Duro-Tak@ 87–2287, in addition to increasing drug release efficiency by a factor of about 5. Pharmacokinetic evaluation demonstrated that the HPR group had >4-fold (Tulobuterol TUL) and 3-fold (Diclofenac DIC) more area under the blood drug concentration curve (AUC) than the commercial TUL and DIC patches in the absence of added excipients and a significantly prolonged mean residence time (MRT) of >4-fold (TUL) and 3-fold (DIC), demonstrating the potential for highly efficacious and prolonged dosing. Furthermore, its safety and mechanical properties meet the requisite standards. Mechanistic inquiries unveiled that both acidic and basic drugs establish hydrogen bonds with HPR and become encapsulated within supramolecular helical structures. The supramolecular helical structures, significantly elevated both the enthalpy of the drug-HPR and entropy of the drugs release, thereby substantially enhancing drug delivery efficiency. In summary, HPR enabled a significant simultaneous enhancement of drug loading and drug delivery, which, together with its unique spatial structure, would contribute to the development of TDDS. In addition, the establishment of rhamnose-induced supramolecular helical structures would provide innovative pathways for different drug delivery systems. [Display omitted] [ABSTRACT FROM AUTHOR]

Skin electroporation for drug delivery involves the application of Pulsed Electric Fields (PEFs) on the skin to disrupt its barrier function in a temporary and non-invasive manner, increasing the uptake of drugs. It represents a potential alternative to delivery methods that are invasive (e.g. injections) or limited. We have developed a drug delivery system comprising nanocomposite hydrogels which act as a reservoir for the drug and an electrode for applying electric pulses on the skin. In this study, we employed a multi-scale approach to investigate the drug delivery system on a mouse skin model, through electrical measurements, numerical modeling and fluorescence microscopy. The Electrical properties indicated a highly non-linear skin conductivity behavior and were used to fine-tune the simulations and study skin recovery after electroporation. Simulation of electric field distribution in the skin showed amplitudes in the range of reversible tissue electroporation (400–1200 V/cm), for 300 V PEF. Fluorescence microscopy revealed increased uptake of fluorescent molecules compared to the non-pulsed control. We reported two reversible electroporation domains for our configuration: (1) at 100 V PEF the first local transport regions appear in the extracellular lipids of the stratum corneum, demonstrated by a rapid increase in the skin's conductivity and an increased uptake of lucifer yellow, a small hydrophilic fluorophore and (2) at 300 V PEF, the first permeabilization of nucleated cells occurred, evidenced by the increased fluorescence of propidium iodide, a membrane-impermeable, DNA intercalating agent. Skin electroporation for transdermal drug delivery assessed by electrical measurements, numerical modeling and delivery of fluorescent molecules. [Display omitted] • Nanocomposite hydrogels function as drug reservoirs and electrodes. • Integrated electrical measurements, numerical modeling & molecule delivery. • Skin resistance drops with electric field strength. • Stratum corneum barrier disruption at 100 V. • Cell membrane permeabilization at 300 V in viable skin. [ABSTRACT FROM AUTHOR]

Nowadays, effective immunotherapy against triple-negative breast cancer (TNBC) remains challenging due to the immunosuppressive tumor microenvironment. Immune checkpoint inhibitor is mostly employed to restore the activity of tumor-specific immune cells, which however brings little therapeutic outcome owing to the limited number of tumor-infiltrating CD8+ T cells and the inefficient delivery of immune drugs to the tumor tissue. Aiming to solve these problems, we herein constructed a tailor-made dissolving microneedle co-encapsulating the TLR7/8 agonist R848 and the immune checkpoint inhibitor aPD-1, termed αNP-RNP@DMN, and fabricated it as a transdermal drug delivery system. This well-designed microneedle patch, endowed with efficient tumor drug delivery ability, was able to mature tumor-infiltrating dendritic cells (TIDCs) and further promote the infiltration of CD8+ T cells into the tumor tissue with the aid of R848. Moreover, the introduction of aPD-1 blocked the programmed cell death protein 1/programmed cell death ligand 1(PD-1/PD-L1) immune checkpoints, synergistically reversing the immunosuppressive microenvironment of TNBC. In vivo therapeutic results demonstrated that αNP-RNP@DMN not only significantly prolonged the survival time of 4T1 tumor-bearing mice, but also inhibited tumor recurrence and lung metastasis after surgery, implying the great potential of this effective drug delivery system for enhanced immunotherapy of superficial tumors. The limited number of tumor-infiltrating CD8+ T cells and the inefficient delivery of immune drugs to the tumor tissue hinder the effective immunotherapy of triple-negative breast cancer (TNBC). Herein, a dissolving microneedle co-encapsulating TLR7/8 agonist R848 and immune checkpoint inhibitor aPD-1 was developed and fabricated as a transdermal drug delivery system. This tailor-made microneedle patch not only promoted drug accumulation in tumor sites in a safe and painless manner, but also lifted the immune-suppressive state of tumor-infiltrating dendritic cells (TIDCs). The activated TIDCs further enhanced T-cell infiltration into the tumor tissue, thus successfully boosting the therapeutic efficacy of aPD-1. This study demonstrated that this well-designed microneedle patch could be served as an effective drug delivery system for enhanced immunotherapy of TNBC. [Display omitted] [ABSTRACT FROM AUTHOR]

To control hypertension, long-term continuous antihypertensive therapeutics are required and five classes of antihypertensive drugs are frequently involved, including diuretics, β-blockers, calcium channel blockers, angiotensin II receptor blockers, and angiotensin-converting enzyme inhibitors. Although with demonstrated clinical utility, there is still room for the improvement of many antihypertensive drugs in oral tablet or capsule dosage form, in terms of reducing systemic side effects and first-pass hepatic drug uptake. Meanwhile, nanocarrier-mediated transdermal drug delivery systems have emerged as a powerful tool for various disease treatments. With benefits such as promoting patient compliance for long-time administration, enhancing skin permeability, and reducing systemic side effects, these systems are reasonably investigated and developed for the transdermal delivery of multiple antihypertensive drugs. This review aims to summarize the literature relating to nanosystem-based transdermal antihypertensive drug delivery and update recent advances in this field, as well as briefly discuss the challenges and prospects of engineering transdermal delivery nanosystems for hypertension treatment. [ABSTRACT FROM AUTHOR]

Microneedles have emerged as a promising platform for transdermal drug delivery with prominent advantages, such as enhanced permeability, mitigated pain, and improved patient adherence. While microneedles have primarily been employed for delivering small molecules, nucleic acids, peptides, and proteins, recent researches have demonstrated their prospect in combination with cell therapy. Cell therapy involving administration or transplantation of living cells (e.g. T cells, stem cells, and pancreatic cells) has gained significant attention in preclinical and clinical applications for various disease treatments. However, the effectiveness of systemic cell delivery may be restricted in localized conditions like solid tumors and skin disorders due to limited penetration and accumulation into the lesions. In this perspective, an overview of recent advances in microneedle‐assisted cell delivery for immunotherapy, tissue regeneration, and hormone modulation, with respect to their mechanical property, cell loading capacity, as well as viability and bioactivity of the loaded cells is provided. Potential challenges and future perspectives with microneedle‐mediated cell therapy are also discussed. [ABSTRACT FROM AUTHOR]