Drug Delivery Patch Research Articles

Perspective: Materials and Electronics Gaps in Transdermal Drug Delivery Patches

Abstract Transdermal drug delivery systems offer a noninvasive method of delivering drugs through the skin surface, which circumvents problems associated with metabolic breakdown, uncontrollable biodistribution after initial drug administration, and limited patient compliance. The most common implement for transdermal drug delivery is the transdermal patch (TDP), which are flexible, medicated adhesive patches that can be placed on any available skin surface for targeted delivery. In this perspective, we summarize the most recent advancements in transdermal drug delivery patches and highlight gaps that can be filled with advanced sensor development.

Application of high-polarity hydroxyl polyacrylate pressure sensitive adhesive in rizatriptan transdermal drug delivery patch

This study aimed to design a rizatriptan (RIZ) transdermal patch by combining of high-polarity hydroxyl pressure sensitive adhesive (PSA) AAOH-45 with an ion-pair strategy and investigate the molecular mechanism of high content hydroxyl PSA to enhance drug-PSA miscibility. RIZ free base, ion-pair complexes and PSAs containing hydroxyl group were prepared and characterized. Formulation factors including counter-ions, PSAs, drug-loading and others were optimized through single-factor studies and evaluated through pharmacokinetic studies and skin irritation tests. The properties of high polarity PSA and molecular mechanism of drug-PSA miscibility were investigated through molecular simulation, FTIR spectra, 13C NMR spectra, DSC, and rheology study. The optimized formulation contained 20 % (w/w) RIZ-OA (Rizatriptan-Oleic acid), 80 % AAOH-45 (w/w) as the matrix, and had a thickness of 90 μm. Compared with the oral group (MRT0-t = 5.96 ± 0.97 h) and the control patch group (MRT0-t = 11.30 ± 1.78 h), the pharmacokinetic behavior of the optimization group demonstrated sustained drug delivery behavior (MRT0-t = 20.21 ± 0.61 h) with no irritation phenomenon. The miscibility of RIZ with PSAs was positively correlated with the mass percentage of 2-HEA. Higher polar similarity, lower flowability, and stronger intermolecular interaction were responsible for the higher compatibility of high hydroxyl PSA with the drug. This study provided a reference for increasing the drug-loading in PSA and developing RIZ patch.

Magnetic Liquid Gating Valve Terminal for Patterned Droplet Generation and Transportation of Highly Viscous Bioactive Fluids.

As an open microfluidic technology with excellent anti-fouling and energy-saving properties, liquid gating technology can selectively separate or transfer multiphase fluids, which has shown great application value in the field of biomedical engineering. However, no study has demonstrated that liquid gating technology has the ability to transfer high-viscosity fluids and biologically active substances, and current liquid gating valves are unable to realize smart-responsive pulsed-patterned transfer, which severely limits their application scope. In this paper, liquid gating technology is combined with magnetically responsive materials to prepare a liquid-based magnetic porous membrane (LMPM) with excellent magnetostatic deformation capability and antifouling properties. On this basis, a magnetic liquid gating valve terminal (MLGVT) with patterning transfer capability is developed, and the feasibility of liquid gating technology for transferring high-viscosity fluids and hydrogel bioinks is explored. Meanwhile, a flexible MLGVT is prepared and realized for targeted drug delivery. This study expands the potential of liquid gating technology for drug delivery, cellular transport and smart patches.

PSIII-28 Evaluation of tissue and plasma meloxicam concentrations using a microneedle patch for drug delivery

Abstract The objective of this study was to evaluate plasma and ear tissue meloxicam concentrations when the drug was delivered using two different formulations of a microneedle patch placed on the back of the ear. Nursing pigs [n = 10; body weight (BW) = 3.64 ± 0.32 kg) from 1 litter were assigned randomly to 1 of 2 treatment groups. Patches delivered 2.5 mg of meloxicam/kg BW to pigs regardless of formulation, with the differences in patches being based on type of polymer located on the microneedles and base of the patch. Treatment groups were: 1) pigs receiving a microneedle patch with collagen, polyvinyl alcohol (PVA), and meloxicam on the microneedles, with PVA and chitosan on the base (n = 6 pigs; Patch A); and 2) pigs receiving a microneedle patch with chitosan, PVA, and meloxicam on the microneedles, with collagen and PVA on the base (n = 4 pigs; Patch B). During the study, pigs remained in the crate with the sow and littermates. An Estrotect Breeding Indicator strip was used to adhere the microneedle patch on the ear of the pigs. Blood was collected at study initiation prior to patch administration (0 h) and 24 and 48 h for plasma meloxicam analysis. To evaluate tissue meloxicam concentrations, 3 pigs that received Patch A and 2 pigs that received Patch B were humanely euthanized after blood collection and patch removal at 24 and 48 h, with the entirety of the ear removed for analysis. Statistical analyses were performed using the MIXED procedure of SAS 9.4 (Cary, NC) to assess the effects of treatment, hour, and treatment × hour interaction. Statistical significance was determined at P ≤ 0.05, with tendencies at 0.05 < P ≤ 0.1. There were no differences (P = 0.83) between patch formulations for tissue meloxicam concentrations (Patch A = 6.55 ± 2.12 ng/mg; Patch B = 7.32 ± 2.60 ng/mg). Plasma concentrations were not detectable at any time point, but tissue concentrations of meloxicam were detectable for pigs that received either patch formulation at 24 (5.44 ± 2.37 ng/mg) and 48 h (8.42 ± 2.37 ng/mg). There were no differences (P = 0.41) between patch formulations for tissue meloxicam concentrations at either timepoint, nor was there an interaction of patch formulation and hour (P = 0.73). It is unknown why the meloxicam did not diffuse from the ear tissue into the plasma; however, further studies will focus on applying the microneedle patch at different areas on the animal to allow for optimal diffusion through the skin and into blood circulation for pain mitigation in livestock animals.

Trilayered nanocellulose-based patches loaded with acyclovir and hyaluronic acid for the treatment of herpetic lesions

This study focuses on the preparation of layered bacterial nanocellulose (BNC) patches for drug delivery and wound healing in the context of herpes labialis. Nanostructured patches were prepared by selective aqueous diffusion of acyclovir (ACV, antiviral drug), hyaluronic acid (HA, skin healing promoter), and glycerol (GLY, plasticizer and humectant) in the BNC network, followed by assembly into trilayered patches with ACV on the central layer of the patch (ACVT) or divided between two layers (ACVH), to modulate drug release. Both patches showed good layers' adhesion and thermal stability (125 °C), UV barrier properties, good static (Young's modulus up to 0.9 GPa (dry) and 0.7 GPa (wet)) and dynamic mechanical performance, and adhesion strength (21 kPa) comparable to or higher than other materials and commercial adhesives for wound healing. In vitro drug dissolution showed faster ACV release from the ACVH patch (77 ± 5 %, 10 min) than from the ACVT one (50 ± 7 %), suggesting efficient drug delivery. ACVH closely resembled a commercial cream formulation in terms of release and permeation profiles. The patches were non-cytotoxic toward L929 fibroblasts, promoting cell adhesion and wound closure (in vitro). These results underscore the dual-action potential of the layered patches for managing herpetic lesions.

A Split-Face Comparison of Novel Microneedle Patch versus Botulinum Toxin-A and Microneedle Patch for Improvement in Undereye Skin Texture

(1) Background: The emergence of microneedle patch technology and its development as a transdermal drug delivery platform have shown proven results in improving skin texture and appearance. This study was conducted to determine the efficacy of the microneedle patch (MNP)-only cosmesis of undereye skin texture and wrinkles against patch cosmesis with diluted botulinum toxin-A. (2) Methods: A total of 23 Thai females volunteered for this prospective clinical trial. Each participant was treated according to a split-face design, with the application of diluted botulinum toxin-A through MNP technology to the right undereye and a normal saline MNP application to the left undereye. Test areas were recorded at baseline and 2, 4, 8, 12, and 16 weeks after the initial treatment. (3) Results: Botulinum toxin-A was successfully delivered to the skin by MNP technology. After the initial treatment, these novel transdermal drug delivery patches significantly improved infraorbital hollowness at week 8 and wrinkles at week 16. In addition, the skin surface was markedly enhanced, with no adverse effects observed during the trial. (4) Conclusions: Novel MNPs are an effective and safe technology for use in the management of undereye skin aging. Combination treatment with botulinum toxin-A-impregnated devices gave a higher patient satisfaction than MNPs alone.

Chitosan mediated smart photodynamic therapy based novel drug delivery systems- a futuristic view

In order to improve the pharmacological and therapeutic properties of drugs, researchers have attempted numerous novel approaches, such as stimuli-responsive systems, and targeted drug delivery systems. These systems can be attempted by nano-based drug delivery systems involving biocompatible polymers. One among which is chitosan, a linear polysaccharide, a promising potential polymer that gained interest in delivering challenging drugs. Chitosan can encapsulate and release the drugs in a controlled/sustained manner. Chitosan can be used to develop a variety of drug delivery carriers, including films, gels, nanoparticles, nanodispersions, nanomicelles, and patches. In this regimen, minimally invasive photodynamic therapy has recently gained much interest in treating vascular diseases, including cancer, ocular diseases, microbial infections, skin disorders, etc. Photodynamic therapy utilizes light excited at a specific wavelength, eliciting singlet oxygen production. Self-lighting photodynamic therapy and combination-based photodynamic therapy also offer synergistic effects. Photodynamic therapy is more selective and specific, which may offer treatment for deep-seated diseased tissues compared to conventional therapeutic modalities. Light-activated novel drug delivery formulations have been reported using various biocompatible polymers, including chitosan. Chitosan offers its effectiveness as mucoadhesiveness, tissue penetrability, antioxidant, antimicrobial properties, supports in singlet oxygen generation, and shown its benefits in photodynamic therapy. Therefore, this review presents numerous applications of chitosan-based light-activated drug delivery systems with particular emphasis on their patents and clinical trials. The literature has been collected and compiled using various search resources such as Science Direct, J-Gate, Google Scholar, PubMed, and research data.

Novel nano-in-micro fabrication technique of diclofenac nanoparticles loaded microneedle patches for localised and systemic drug delivery

Diclofenac, a nonsteroidal anti-inflammatory drug, is commonly prescribed for managing osteoarthritis, rheumatoid arthritis, and post-surgical pain. However, oral administration of diclofenac often leads to adverse effects. This study introduces an innovative nano-in-micro approach to create diclofenac nanoparticle-loaded microneedle patches aimed at localised, sustained pain relief, circumventing the drawbacks of oral delivery. The nanoparticles were produced via wet-milling, achieving an average size of 200 nm, and then incorporated into microneedle patches. These patches showed improved skin penetration in ex vivo tests using Franz-cell setups compared to traditional diclofenac formulations. In vivo tests on rats revealed that the nanoparticle-loaded microneedle patches allowed for quick drug uptake and prolonged release, maintaining drug levels in tissues for up to 72 h. With a systemic bioavailability of 57 %, these patches prove to be an effective means of transdermal drug delivery. This study highlights the potential of this novel microneedle delivery system in enhancing the treatment of chronic pain with reduced systemic side effects.

Thermo-responsive microneedles patch for transdermal drug delivery via squeezing in diabetic foot ulcers

Microneedle (MN) patches could be a promising treatment for diabetic foot ulcers that plague thousands of people worldwide. While reducing skin resistance or increasing driving force can accelerate the efficiency of transdermal drug delivery with conventional MN patches, it can create toxic chemical residues or require the help of additional devices. Herein, a thermo-responsive microneedles patch (TMN) with high biocompatibility without additional equipment is proposed. The TMN consisted of a bilayer microneedles composed of sodium alginate (SA)-g-poly(N-isopropylacrylamide) layer (SA-g-PNIPAM) loaded with sucrose octasulfate sodium salt (SOS) and hyaluronic acid layer and a polycaprolactone/chitosan nanofiber membrane loading with tetracycline hydrochloride (TH) and SOS. PNIPAM accelerates drug release by extruding the drug through a volumetric phase transition in response to temperature changes, and TH and SOS promote wound healing by inhibiting bacterial growth and promoting vascular regeneration and epithelial formation. The results showed that the drug release of TMN was significantly faster, with the drug release rate of more than 80% in the 10th h, and the antibacterial rate of TMN could reach 800%. In addition, TMN had good biocompatibility and good healing effects in vivo, which may be helpful for the design of multifunctional dressings in the future.

Feasibility assessment of polyvinyl alcohol-based bioresorbable cardiovascular stents manufactured via solvent-cast direct writing extrusion

BackgroundBioresorbable stents represent a promising approach in cardiovascular interventions compared to drug-eluting stents. Additive manufacturing, particularly ink deposition, offers customization and versatility. This study delves into the potential of solvent cast direct-write 3D printing to fabricate cardiovascular stents using environmentally friendly solvents. MethodologyPolyvinyl alcohol, a biocompatible synthetic polymer that dissolves in water, was investigated as a suitable material for stent fabrication. The polymer was deposited on a rotating mandrel and subsequently crosslinked to establish a pseudostable state. Test specimens and stents were fabricated for characterization of both the material and stent dynamics. ResultsThis outcome is potentially suitable for deployment in the human body environment and adaptable to various biomedical applications, such as drug delivery patches or implants. The research optimized the fabrication of various stent geometries using polyvinyl alcohol and evaluated the kinetics of the working environment of these stents. Specifically, the 8-cell diamond stent showed remarkable characteristics, such as a high overexpansion of more than 0.5 mm, a compression force of 0.02 N and an elastic recovery of 88.85 %, with a strut thickness of 50.25 μm. Additionally, the study discusses the possibility of sterilizing polyvinyl alcohol with different methods, ethanol and autoclave were selected. ConclusionsThe results indicate that autoclaving leads to an increase in crystallinity. This yields a decrease in water absorption and an increase in mechanical properties. These results suggest that polyvinyl alcohol-based stents fabricated by solvent-cast direct writing are potential candidates for bioresorbable stent design.

Nanofiber Hydrogel Drug Delivery System for Prevention of Postsurgical Intestinal Adhesion.

Intestinal adhesion is one of the complications that occurs more frequently after abdominal surgery. Postsurgical intestinal adhesion (PIA) can lead to a series of health problems, including abdominal pain, intestinal obstruction, and female infertility. Currently, hydrogels and nanofibrous films as barriers are often used for preventing PIA formation; however, these kinds of materials have their intrinsic disadvantages. Herein, we developed a dual-structure drug delivery patch consisting of poly lactic-co-glycolic acid (PLGA) nanofibers and a chitosan hydrogel (NHP). PLGA nanofibers loaded with deferoxamine mesylate (DFO) were incorporated into the hydrogel; meanwhile, the hydrogel was loaded with anti-inflammatory drug dexamethasone (DXMS). The rapid degradation of the hydrogel facilitated the release of DXMS at the acute inflammatory stage of the early injury and provided effective anti-inflammatory effects for wound sites. Moreover, PLGA composite nanofibers could provide sustained and stable release of DFO for promoting the peritoneal repair by the angiogenesis effects of DFO. The in vivo results indicated that NHP can effectively prevent PIA formation by restraining inflammation and vascularization, promoting peritoneal repair. Therefore, we believe that our NHP has a great potential application in inhibition of PIA.

A strong, silk protein-inspired tissue adhesive with an enhanced drug release mechanism for transdermal drug delivery

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. Statement of significanceA 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.

Physicochemical, structural and biological characterisation of poly(3-hydroxyoctanoate) supplemented with diclofenac acid conjugates — Harnessing the potential in the construction of materials for skin regeneration processes

This study involved creating oligomeric conjugates of 3-hydroxy fatty acids and diclofenac, named Dic-oligo(3HAs). Advanced NMR techniques confirmed no free diclofenac in the mix. We tested diclofenac release under conditions resembling healthy and chronic wound skin. These oligomers were used to make P(3HO) blends, forming patches for drug delivery. Their preparation used the solvent casting/porogen leaching (SCPL) method. The patches' properties like porosity, roughness, and wettability were thoroughly analysed. Antimicrobial assays showed that Dic-oligo(3HAs) exhibited antimicrobial activity against reference (S. aureus, S. epidermis, S. faecalis) and clinical (Staphylococcus spp.) strains. Human keratinocytes (HaCaT) cell line tests, as per ISO 10993-5, showed no toxicity. A clear link between material roughness and HaCaT cell adhesion was found. Deep cell infiltration was verified using DAPI and phalloidin staining, observed under confocal microscopy. SEM also confirmed HaCaT cell growth on these scaffolds. The strong adhesion and proliferation of HaCaT cells on these materials indicate their potential as wound dressing layers. Additionally, the successful diclofenac release tests point to their applicability in treating both normal and chronic wounds.

Effect of transdermal drug delivery patches on the stratum corneum: in vivo inspection with a handheld terahertz probe.

Transdermal drug delivery patches are a good alternative to hypodermic drug injection. The drug delivery efficiency depends strongly on the hydration of the skin under treatment, and therefore, it is essential to study the effects on the skin induced by the application of these medical-grade patches. Terahertz (THz) spectroscopy shows great promise for non-invasive skin evaluation due to its high sensitivity to subtle changes in water content, low power and non-ionizing properties. In this work, we study the effects of transdermal drug delivery patches (three fully occlusive and three partially occlusive) applied on the upper arms of ten volunteers for a maximum period of 28 h. Three different levels of propylene glycol (0 %, 3 % and 6 %) are added to the patches as excipient. By performing multilayer analysis, we successfully retrieve the water content of the stratum corneum (SC) which is the outermost layer of skin, as well as its thickness at different times before and after applying the patches. This study demonstrates the potential of using THz sensing for non invasive skin monitoring and has wide applications for skin evaluation as well as the development of skin products.

Potential of multifunctional electrospun nanofibers in cancer management

Abstract A controlled and sustained release of drugs is much more desirable and beneficial when dealing with cancer, as such drugs also harm normal cells. Available anticancer drugs used in chemotherapy are associated with severe side effects due to high dosage requirements. Electrospun nanofibers have an extensive surface area, controllable pore size, and tunable drug release profiles, which make these nanofibers promising candidates in the medical field. Electrospun fibrous matrices are increasingly used in cancer research as patches for drug delivery in living organisms and as scaffolds for cancer modeling in the lab. Towards these applications, nanofibers synthesized by electrospinning have exhibited great clinical potential as a biomimetic tumor microenvironment model for drug screening, a controllable platform for localized, prolonged drug release for cancer therapy, and a human cancer diagnostic tool for capture and isolation of circulating tumor cells in the bloodstream and detection of cancer-associated biomarkers. This review briefly describes most of the materials used in electrospinning. Then, we discuss two ways that electrospinning is used to fight cancer: first, as patches with anticancer agents for therapeutic cargo delivery, and second, as three-dimensional fiber for filtering and detecting cancers.

Toward chronopharmaceutical drug delivery patches and biomaterial coatings for the facilitation of wound healing

Implantation of a biomaterial entails a form of injury where the integration of the implant into the host tissue greatly depends on the proper healing of the wound. Wound healing, itself, consists of a number of physiological processes, each occurring within a characteristic time window. A composite, multilayered polymeric drug delivery carrier for adhesion to the wound site and its supply with molecules released at precise time windows at which the stages in the healing process that they target occur is conceptualized here. We also present a simplified version of one such multilayered composite fabricated by a combination of solvent casting and dip coating, comprising the base poly(ε-caprolactone) layer reinforced with hydroxyapatite nanoparticles, poly(glutamic acid) mesolayer and poly-l-lysine surface layer, each loaded with specific small molecules and released at moderately distinct timescales, partially matching the chronology of wound healing. To that end, the base layer proved suitable for the delivery of an anti-inflammatory molecule or an angiogenic agent, the mesolayer appeared appropriate for the delivery of an epithelialization promoter or a granulation factor, and the adhesive surface layer interfacing directly with the site of injury showed promise as a carrier of a vasodilator. The drug release mechanisms were diffusion-driven, suggesting that the drug/carrier interaction is a key determinant of the release kinetics, as important as the nature of the polymer and its hydrolytic degradation rate in the aqueous medium. Morphological and phase composition analyses were performed, along with the cell compatibility ones, demonstrating solid adhesion and proliferation of both transformed and primary fibroblasts on both surfaces of the composite films. The design of the multilayered composite drug delivery carriers presented here is prospective, but requires further upgrades to achieve the ideal of a perfect timing of the sequential drug release kinetics and a perfect resonance with the physiological processes defining the chronology of wound healing.

Chlorogenic acid supported strontium polyphenol networks ensemble microneedle patch to promote diabetic wound healing

Delayed or non-healing of diabetic wounds is a significant complication, often attributed to high glucose-induced M1 macrophage accumulation, impaired angiogenesis, and reactive oxygen species (ROS) buildup. Addressing this, we introduced a strontium polyphenol network microneedle patch (SrC-MPNs@MN-PP) for percutaneous drug delivery. This patch, formulated with polymer poly(γ-glutamic acid) (γ-PGA) and epsilon-poly-l-lysine (ε-PLL), incorporates strontium polyphenol networks (SrC-MPNs). The release of chlorogenic acid (CGA) from SrC-MPNs not only neutralizes ROS, but strontium ions also foster angiogenesis. Consequently, SrC-MPNs@MN-PP can ameliorate the diabetic wound microenvironment and expedite healing.

Transport Mechanism of Paracetamol (Acetaminophen) in Polyurethane Nanocomposite Hydrogel Patches-Cloisite® 30B Influence on the Drug Release and Swelling Processes.

This article describes the swelling and release mechanisms of paracetamol in polyurethane nanocomposite hydrogels containing Cloisite® 30B (organically modified montmorillonite). The transport mechanism, swelling and release processes of the active substance in nanocomposite matrix were studied using gravimetric and UV-Vis spectroscopic methods. Swelling and release processes depend on the amount of clay nanoparticles in these systems and the degree of crosslinking of PU/PEG/Cloisite® 30B hydrogel nanocomposites. The presence of clay causes, on the one hand, a reduction in free volumes in the polymer matrices, making the swelling process less effective; on the other hand, the high swelling and self-aggregation behavior of Cloisite® 30B and the interactions of paracetamol both with it and with the matrix, cause a change in the transport mechanism from anomalous diffusion to Fickian-like diffusion. A more insightful interpretation of the swelling and release profiles of the active substance was proposed, taking into account the "double swelling" process, barrier effect, and aggregation of clay. It was also proven that in the case of modification of polymer matrices with nanoparticles, the appropriate selection of their concentration is crucial, due to the potential possibility of controlling the swelling and release processes in drug delivery patches.

Design of a tulobuterol patch with improved mechanical properties: effect of transdermal permeation enhancers on the release process of metal ligand-based acrylic pressure-sensitive adhesives.

The aim of this study was to design a tulobuterol (TUL) patch with good penetration behavior and mechanical properties. Particular attention was paid to the effect of transdermal permeation enhancers on the release process of metal ligand-based acrylic pressure-sensitive adhesive (AA-NAT/Fe3+). The type and dosage of the enhancers were screened by in vitro transdermal penetration in rat skin. The optimized formulation was evaluated in a pharmacokinetic study in rats. Furthermore, the molecular mechanism by which Azone (AZ) improves the release rate of TUL from AA-NAT/Fe3+ was investigated by FT-IR, shear strength test, rheological study, and molecular simulation. As a result, the optimized formula using AA-NAT/Fe3+ showed better mechanical properties compared to commercial products. Meanwhile, the AUC0-t and Cmax of the optimized patch were 1045 ± 89ng/mL·h and 106.8 ± 28.5ng/mL, respectively, which were not significantly different from those of the commercial product. In addition, AZ increased the mobility of the pressure-sensitive adhesive (PSA) rather than decreasing the drug-PSA interaction, which was the main factor in enhancing TUL release from the patch. In conclusion, a TUL transdermal drug delivery patch was successfully developed using metal-coordinated PSA, and a reference was provided for the design of metal-coordinated acrylic PSA for transdermal patch delivery applications.

An Intrinsically Magnetic Epicardial Patch for Rapid Vascular Reconstruction and Drug Delivery.

Myocardial infarction (MI) is a major cause of mortality worldwide. The major limitation of regenerative therapy for MI is poor cardiac retention of therapeutics, which results from an inefficient vascular network and poor targeting ability. In this study, a two-layer intrinsically magnetic epicardial patch (MagPatch) prepared by 3D printing with biocompatible materials like poly (glycerol sebacate) (PGS) is designed, poly (ε-caprolactone) (PCL), and NdFeB. The two-layer structure ensured that the MagPatch multifariously utilized the magnetic force for rapid vascular reconstruction and targeted drug delivery. MagPatch accumulates superparamagnetic iron oxide (SPION)-labelled endothelial cells, instantly forming a ready-implanted organization, and rapidly reconstructs a vascular network anastomosed with the host. In addition, the prefabricated vascular network within the MagPatch allowed for the efficient accumulation of SPION-labelled therapeutics, amplifying the therapeutic effects of cardiac repair. This study defined an extendable therapeutic platform for vascularization-based targeted drug delivery that is expected to assist in the progress of regenerative therapies in clinical applications.