Drug Delivery Patch Research Articles

Printable personalized drug delivery patch for the topical therapy of skin diseases

<h2>Summary</h2> Topical drug delivery is a favored route for treating skin diseases. However, many challenges remain, such as the precise drug delivery to specific locations and the tailorable control of the local therapeutic dosage. Here, we describe a personalized drug delivery system based on a printable patterned patch by printing drugs using a modified inkjet printer under dermoscopy guidance. A drug-loading layer and a protective layer were spin coated on the substrate to produce the patch. Both fat- and water-soluble drugs could be printed on the patch with high precision and resolution, and local precise drug dose control was achieved according to individual conditions (the location and severity of the lesion). We demonstrated the feasibility of personalized treatment of skin pigmentation with high efficacy and limited side effects using a mouse model. This printable personalized drug delivery patch holds great promise for potential clinical applications, especially for the treatment of skin diseases.

Design, Optimization and Characterization of Combined Ethosomal Transdermal Patch of Glimepiride and Duloxetine Drug Regimen for Diabetes and Associated Neuropathic Pain Management

Background: Diabetic neuropathic pain is the most prevalent type of neuropathic pain and a major consequence of diabetes. A wide range of medications, whether administered alone or in combination, have been found to dramatically decrease neuropathic pain. Objective: This study aimed to develop the glimepiride (GLM) and duloxetine (DUL) ethosomal transdermal drug delivery patches to prolong and improve the discharge of the drug regimen to treat diabetics as well as neuropathic pain associated with it. Methods: Using the solvent casting method, DUL and GLM ethosomal dispersions were formulated by a 32 factorial design. A total of nine formulations were developed considering ethanol (X1) and phospholipid (X2) independent factors, and the formulation was optimized based on entrapment efficiency (Y1) and particle size (Y2). Moreover, size, surface charge, and % entrapment efficiency were characterized. The ethosomal formulations converted into patches were characterized by thickness, folding endurance, in vitro penetrability, and ex vivo skin permeability. Results: The results of thickness, % moisture content, % moisture uptake, and folding endurance were in an acceptable range for all formulations. Based on the in vitro penetrability and ex vivo skin permeability profile, formulation F9 was considered optimized, extending the cumulative drug release of more than 60 % up to 24hrs and skin permeability of more than 200 μg/cm2. Conclusion: The investigation showed that the medication increment transdermal fix of GLM and DUL was a promising path for the therapeutic management of diabetes and diabetic neuropathic pain.

Development of Multilayer Ciprofloxacin Hydrochloride Electrospun Patches for Buccal Drug Delivery.

Bacterial infections in the oral cavity can become a serious problem causing pain, sores and swelling for several weeks. This type of infection could be alleviated using mucoadhesive delivery systems, allowing local administration of the antibiotic to inhibit bacterial spreading. This work reports the development of a multilayer antibiotic patch containing ciprofloxacin hydrochloride (CPX)-loaded electrospun fibers for the treatment of such infections. For this, the release kinetics of the CPX-loaded fibers was modulated using different ratios of polyester blends. The selected reservoir layer was analyzed by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), wide angle x-ray scattering (WAXS) and differential scanning calorimetry (DSC). These analyses confirmed the presence and good distribution of the drug in the fibers and that the drug is in an amorphous state within the reservoir layer. To enhance mucoadhesion whilst ensuring drug directionality, the reservoir layer was assembled to a backing and an adhesive layer. This multilayer patch was assessed in terms of in vitro drug release, adhesion and antimicrobial properties. The multilayer strategy showed excellent antimicrobial properties over time and also a strong adhesion patch time in the volunteers for an average of 7 h. These results highlight the capabilities of multilayer electrospun patches as platforms to treat oral infections.

Nanoclay Reinforced Ternary Blends Based on Biodegradable Polymers for Drug Delivery Application.

In this study, ternary blends based on chitosan, polyvinyl alcohol, and polyethylene glycol reinforced with organically modified montmorillonite (nanoclay) clay were synthesized. These ternary blends were evaluated as transdermal drug delivery patches using tramadol as a model drug. The FTIR study showed interaction among important functional groups and compatibility among the mixing components. Among drug-loaded formulations, composite MA12 shows maximum thermal stability with 27.9% weight residue at 540°C. The prepared formulations exhibited crystalline nature as observed by XRD analysis. SEM studies revealed that there are no gaps and cracks in prepared films and nanoclay was found dispersed in the formulations. The swelling ratio was higher in pH 1.2 as compared to pH 4.5 and pH 6.8 buffers, and there was an increase in swelling with an increase in PVA concentration. Moreover, the drug release test performed in phosphate buffer pH 6.8 showed that tramadol release from nanocomposite films increases with an increase in PEG concentration. Permeation studies indicated that the rate of permeation increased with a decrease in PVA concentration. The permeation rate was found to be higher for samples without nanoclay. The overall results suggest nanocomposite films as excellent candidates for transdermal drug delivery application.

SEDDS-loaded mucoadhesive fiber patches for advanced oromucosal delivery of poorly soluble drugs.

To date, buccal administration of lipophilic drugs is still a major challenge due to their poor solubility in saliva and limited penetration into mucosal tissues. To overcome these limitations, we developed electrospun patches combining the benefits of mucoadhesive fibers and self-emulsifying drug delivery systems (SEDDS). The fiber system comprises a combination of mucoadhesive thiolated polyacrylic acid fibers and SEDDS-loaded fibers fabricated by parallel electrospinning. The resulting mucoadhesive electrospun SEDDS patches were systemically investigated for fiber characteristics, self-emulsification, mucoadhesion, drug penetration into porcine buccal tissue and biocompatibility. The patches showed high encapsulation efficiency for SEDDS without causing fiber defects or leakage. SEDDS incorporation enhanced the spinning process and reduced the fiber diameter and fiber size distribution. Hydration-dependent self-emulsification provided a controlled release of curcumin being encapsulated in nano-scaled o/w emulsion for over 3h. Due to the thiolated polyacrylic acid fibers, the buccal residence time of patches was 200-fold prolonged. Further, they promoted a significantly increased drug penetration into buccal tissue compared to fiber patches without SEDDS. Finally, biocompatibility and improved therapeutic effects of curcumin-loaded patches on human keratinocytes and fibroblasts were confirmed. Mucoadhesive electrospun SEDDS patches represent a promising approach to overcome current challenges in the oromucosal delivery of lipophilic drugs to unlock their full therapeutic potential.

Fabrication and characterization of innovative chitosan/doxorubicin coated3Dprinted microneedle patch for prolonged drug delivery

AbstractIn this study, microneedles (MNs) were successfully fabricated using the 3D printing method, which provides ease of production and reproduction in the desired size. Chi/Dox MNs drug delivery systems containing doxorubicin (Dox) were successfully produced in the presence of glutaraldehyde, which was coated with chitosan (Chi) and used as a crosslinker to prolong the drug release of the produced MNs. The obtained Chi/Dox MNs drug distribution systems were characterized by SEM, FTIR, zeta, contact angle, surface energy, compression test, and drug release tests. With the SEM analyzes performed before and after coating, it was observed that the MNs were in micro dimensions, and the diameters of the MNs tips before and after coating were 41.22 μm and 54.58 μm, respectively. After the compression test, it was analyzed that each MNs could withstand a force of about 76 N. The zeta potentials of Chi and Dox solutions were measured as 8.8 and 21.5 mV, respectively. FTIR, zeta potential, contact angle, and surface energy results confirm the Dox coating and their interactions. It has been observed that Chi/Dox MNs has successfully extended drug release time without drug‐burst, and their use in skin cancer treatment is promising.

Binary ethosomes-based transdermal patches assisted by metal microneedles significantly improve the bioavailability of carvedilol

This study aimed to develop a strategy combining binary ethsomes (BES) and microneedles (MNs) to improve the bioavailability of drugs that are poorly bioavailable by oral administration, such as carvedilol (CL). The formula of BES was optimized by Box-Benhnken Designes from four aspects: particle size, zeta potential, encapsulation efficiency and cumulative release in vitro. The optimized BES was then mixed with polyvinylpyrrolidone and sprayed onto the silk fibroin matrix by electrospray to obtain transdermal drug delivery patches (TDDP). In vitro skin penetration test showed that, TDDP has much better transdermal drug release performance compared with free drugs, and MNs-assisted TDDP (MNs-TDDP) can deliver more drugs to the receiving chamber. In vivo studies indicate that MNs-TDDP can significantly reduce the fluctuation of CL concentration in plasma and increase serum level of NO, thereby lower blood pressure for a longer time. These results suggest that the bioavailability of CL can be greatly improved via administration of MNs-TDDP, compared with the oral route. Considering its advantages of non-invasiveness, convenience and good biosafety, MNs-TDDP has a promising prospect in improving the bioavailability of drugs for treating chronic diseases such as hypertension.

A Review on Transdermal Drug Delivery Patches

Human civilizations have used substances to the skin as cosmetic and therapeutic agents for thousands of years. The skin, on the other hand, was not exploited as a drug delivery method until the twentieth century. The term “transdermal” was first used in 1944 by Merriam Webster, indicating that it is a relatively new notion in medicinal and pharmacological practice. Transdermal medicines are doses that are self-contained and distinct. To produce a systemic effect, drugs are delivered through the skin. Without causing any changes in the drug’s plasma concentration Topical application of medicinal medicines has a number of advantages. There are numerous advantages to this technique of drug delivery over traditional oral and invasive approaches. Also, ensure that the fluid is released in a regulated manner. A medication for a long amount of time. As a result, a variety of chemical and physical approaches to transdermal patch development are being investigated.

Ferroferric oxide loaded near-infrared triggered photothermal microneedle patch for controlled drug release

HypothesisThe drug release efficiency of microneedle is usually slower than that of oral delivery or hypodermic injection, which severely restricts its widespread use. Herein, a Fe3O4-loaded photothermal microneedle (Fe3O4@MN) patch is developed for controlled drug delivery. Under near infrared (NIR) irradiation, the drug loaded on Fe3O4@MN can be quickly released, achieving an enhanced drug release efficiency. ExperimentsThe mechanical property and characterization of Fe3O4@MN were systematically investigated, and the photothermal performance of Fe3O4@MN was also conducted. Moreover, the model-drug-releasing tests and doxycycline hydrochloride releasing tests were carried out to evaluate the drug release performance of Fe3O4@MN under NIR irradiation. FindingsFe3O4@MN has enough mechanical strength to pierce into skins, and the temperature of Fe3O4@MN patch could rapidly increase by 40 ℃ in 1 min under NIR irradiation. In vitro experiment, the release rate of model drug in Fe3O4@MN reached ∼ 80 % in 20 min and the doxycycline hydrochloride release rate of Fe3O4@MN reached ∼ 70 % after 20 min of NIR irradiation, indicating the potential application of the synthesized microneedle patch for transdermal drug delivery. Further penetration test showed that the penetration depth of model drugs carried by Fe3O4@MN patch on the porcine skin under NIR irradiation was 150 – 200 μm longer than that of the patch without Fe3O4 nanoparticles.

Layer-by-Layer Assembly of Lipid Nanobubbles on Microneedles for Ultrasound-Assisted Transdermal Drug Delivery.

Microneedles as a typical device for transdermal drug delivery provide an alternative route for drug administration with minimal digestion by organs and better patient compliance. However, diffusion of passively released drug molecules within the skin tissue mainly depends on the interstitial fluid, which may be affected by different physiological conditions of individuals. Herein, we propose a nanobubble-modified microneedle patch for ultrasound-assisted drug delivery, which provides additional driving force for penetration and diffusion of the drug molecules. Layer-by-layer self-assembled drug-containing nanobubbles on the surfaces of microneedles trigger active drug release upon application of ultrasound. The concomitant microstreaming caused by cavitation effects facilitates the penetration and diffusion of drug molecules in the gelatin gel model and the ex vivo porcine skin model. The proposed drug delivery strategy holds great promise for rapid transdermal drug delivery with enhanced penetration and diffusion of the released drugs.

Polymeric and electrospun patches for drug delivery through buccal route: Formulation and biointerface evaluation

IntroductionOf the various transmucosal routes which are being considered for extended and controlled drug delivery, buccal route is superior to other methods owing to high administrability and milder environment for drug absorption. In this direction, mucoadhesive buccal films of venlafaxine were fabricated using a combination of biocompatible polymers. AimThe main objective of the study was to standardize an optimized formulation of polyvinyl alcohol, sodium carboxymethyl cellulose and sodium alginate that would lead to sustained drug delivery in the form of buccal patches. MethodsVarying polymeric concentrations were utilized for the fabrication of buccal patches via solvent casting method. The physical parameters were evaluated, followed by in vitro drug release studies. The electrospun nanofibers were prepared for optimized formulations and the buccal delivery system was compared to oral and intravenous routes for absorption, distribution, and elimination during in vivo studies using venlaflaxine. ResultsThe patches had high tensile strength with uniform drug content and surface pH in the range of 6.28–6.88. The release of drug was steady witha maximum release of 89.97% at 5 h. The negative hemolytic and cytotoxicity studies with TR146 cells over a range of concentrations indicated biocompatibility of the mucoadhesive patch with human tissues. The pharmacokinetics of the buccal patch of the radiolabeled drug, 99mTc-venlaflaxine, displayed favorable release pattern. The radiolabeled patch attached to rabbit buccal mucosa displayed high retention with controlled drug release as indicated by the Cmax and T1/2 values (19.94 ng/ml and 3 h). The drug release mechanism corresponded to a pure fickian diffusion-controlled mechanism following Higuchi's model. Electrospun fibrous patch of the drug had a 10% higher drug release than solvent cast patch. ConclusionIn vitro and in vivo data indicate that the polymeric system was successfully optimized for sustained drug release for about 5 h in a continuous manner with electrospun fibrous patch showing 10% increase in drug release studies. The patches displayed ideal physical and biocompatibility characteristics. This polymeric combination can therefore be further utilized for development of novel drug delivery systems with sustained drug release pattern.

Photothermal Responsive Microspheres‐Triggered Separable Microneedles for Versatile Drug Delivery

AbstractMicroneedle (MN) patches are promising stratagems for transdermal drug delivery owing to its minimal invasiveness and portability. Particularly, separable MN patches attract more attention for durable and long‐term drug delivery. Here, a new strategy for designing controllably separable MN patches by integrating photothermal responsive phase‐changing microspheres (MPs) into conical hydrogel MNs, is presented. Such MPs consist of near‐infrared (NIR)‐responsive black‐phosphorus (BP) and phase‐changing gelatin (GT), and are fabricated using a simple capillary microfluidic device. When the composite MN patch is exposed to NIR, the contained BP/GT MPs can transform light into heat, increase local temperature, turn into a liquid state, and form cavities in MNs, resulting in the convenient detachment of the backing plate and the needles by shear force. Subsequently, the embedded needles can sustainably release the drug. In addition to intelligently controlling the detachment of MNs, the BP/GT MPs can load macromolecular drugs and release them in response to NIR stimulation. Results further demonstrated that such controllably separable MN patch can effectively load and release two drugs to ameliorate disease progression for systemic lupus erythematosus treatment. These features indicate the practical values of controllably separable MN patches for versatile drug delivery and clinical applications.

Monitoring the Effect of Transdermal Drug Delivery Patches on the Skin Using Terahertz Sensing.

Water content of the skin is an important parameter for controlling the penetration rate of chemicals through the skin barrier; therefore, for transdermal patches designed for drug delivery to be successful, the effects of the patches on the water content of the skin must be understood. Terahertz (THz) spectroscopy is a technique which is being increasingly investigated for biomedical applications due to its high sensitivity to water content and non-ionizing nature. In this study, we used THz measurements of the skin (in vivo) to observe the effect of partially and fully occlusive skin patches on the THz response of the skin after the patches had been applied for 24 h. We were able to observe an increase in the water content of the skin following the application of the patches and to identify that the skin remained hyper-hydrated for four hours after the removal of the fully occlusive patches. Herein, we show that THz spectroscopy has potential for increasing the understanding of how transdermal patches affect the skin, how long the skin takes to recover following patch removal, and what implications these factors might have for how transdermal drug patches are designed and used.

Multi-material 3D printing of programmable and stretchable oromucosal patches for delivery of saquinavir

Oromucosal patches for drug delivery allow fast onset of action and ability to circumvent hepatic first pass metabolism of drugs. While conventional fabrication methods such as solvent casting or hot melt extrusion are ideal for scalable production of low-cost delivery patches, these methods chiefly allow for simple, homogenous patch designs. As alternative, a multi-material direct-ink-write 3D printing for rapid fabrication of complex oromucosal patches with unique design features was demonstrated in the present study. Specifically, three print-materials: an acidic saquinavir-loaded hydroxypropyl methylcellulose ink, an alkaline effervescent sodium carbonate-loaded ink, and a methyl cellulose backing material were combined in various designs. The CO2 content and pH of the microenvironment were controlled by adjusting the number of alkaline layers in the patch. Additionally, the rigid and brittle patches were converted to compliant and stretchable patches by implementing mesh-like designs. Our results illustrate how 3D printing can be used for rapid design and fabrication of multifunctional or customized oromucosal patches with tailored dosages and changed drug permeation.

Development and evaluation of drug delivery patch for topical wound healing application

Wound treatment remains a challenge to many clinicians because of the complexities of the wound healing process. With the astonishing progress of biomedical engineering during the past few decades, conventional drug delivery systems have been evolved into smart drug delivery systems with stimuli-responsive characteristics. The objective of this study was to develop and evaluate an electromechanically actuated drug dispensation device which can release active pharmaceutical compound in a controlled fashion. Additive manufacturing was employed to design and fabricate the device. Haptic technology was used to provide stimulation for drug release, and Cicatrin was used to evaluate the drug release patterns of device. Drug release study was comprised of in vitro drug release, static study, and the purpose of this study was to develop a compliance chart for different wound conditions. The effectiveness of shortlisted drug regimen from compliance chart was validated through microbial study and animal studies. The results of animal studies were compared with commercially available drug release systems. The results of drug release studies gave different dose regimens for different wound conditions. The effective dose regimen was able to create 1-cm-wide microbial zone of inhibitions. The wound healing rate of mice for commercially available release system for five consecutive days was 10%, 10%, 20%, 40% and 50% and for test device was 10%, 30%, 60%, 90% and 100%. Hence, the device proved its effectiveness and efficacy of dosage regimen for wound healing applications through in vitro, microbial and in vivo studies. In conclusion, this device proved to be an accurate and specific drug delivery system with improved medication and therapeutic outcomes for personalized medication.

An overview of microneedle applications, materials, and fabrication methods.

Microneedle-based microdevices promise to expand the scope for delivery of vaccines and therapeutic agents through the skin and withdrawing biofluids for point-of-care diagnostics – so-called theranostics. Unskilled and painless applications of microneedle patches for blood collection or drug delivery are two of the advantages of microneedle arrays over hypodermic needles. Developing the necessary microneedle fabrication processes has the potential to dramatically impact the health care delivery system by changing the landscape of fluid sampling and subcutaneous drug delivery. Microneedle designs which range from sub-micron to millimetre feature sizes are fabricated using the tools of the microelectronics industry from metals, silicon, and polymers. Various types of subtractive and additive manufacturing processes have been used to manufacture microneedles, but the development of microneedle-based systems using conventional subtractive methods has been constrained by the limitations and high cost of microfabrication technology. Additive manufacturing processes such as 3D printing and two-photon polymerization fabrication are promising transformative technologies developed in recent years. The present article provides an overview of microneedle systems applications, designs, material selection, and manufacturing methods.

Smart Responsive Microarray Patches for Transdermal Drug Delivery and Biological Monitoring.

Traditional drug delivery routes possess various disadvantages which make them unsuitable for certain population groups, or indeed unsuitable for drugs with certain physicochemical properties. As a result, a variety of alternative drug delivery routes have been explored in recent decades, including transdermal drug delivery. One of the most promising novel transdermal drug delivery technologies is a microarray patch (MAP), which can bypass the outermost skin barrier and deliver drugs directly into the viable epidermis and dermis. Unlike traditional MAPs which release loaded cargo simultaneously upon insertion into the skin, stimuli responsive MAPs based on biological stimuli are able to precisely release the drug in response to the need for additional doses. Thus, smart MAPs that are only responsive to certain external stimuli are highly desirable, as they provide safer and more efficient drug delivery. In addition to drug delivery, they can also be used for biological monitoring, which further expands their applications.

Bacterial cellulose nanofibrils-reinforced composite hydrogels for mechanical compression-responsive on-demand drug release

Herein, we propose a cellulose-reinforced hybrid hydrogel system that not only increases mechanical strength, but also allows on-demand drug release. This hybrid hydrogel is specialized by its semi-interpenetrating network structure in which bacterial cellulose nanofibers (BCNFs) penetrate through a polyacrylamide (PAM) mesh. We showed that the interpenetrating BCNFs with a higher aspect ratio of 240 increased the compression strength of PAM/BCNF composite hydrogels approximately 3-fold, compared with that prepared with PAM only, stemming from the reinforcing effect of the rigid natural nanofibers between PAM meshes. We also observed that the swelling kinetics depended on the mechanical properties determined by the BCNF aspect ratio. From further studies on drug release, we demonstrated that the tailored composition of BCNFs with PAM retarded drug release by a factor of two compared to PAM only while enabling on-demand drug release in response to the applied compressive stress. These results highlight that our BCNFs-reinforced hydrogel system can be applied as a mechanical stress-responsive smart drug delivery patch.

Controlling the Friction of Gels by Regulating Interfacial Oxygen During Polymerization

Hydrogel surfaces are of great interest in applications ranging from cell scaffolds and transdermal drug-delivery patches to catheter coatings and contact lenses. In this work, we propose a method to control the surface structure of hydrogels, thereby tailoring their frictional properties. The method is based on oxygen inhibition of the free-radical polymerization reaction during synthesis and enables (i) control of friction over more than an order in magnitude and (ii) spatial control of friction as either a continuous gradient or a distinct pattern. The presented method has successfully been applied to acrylamide-, diacrylate- and methacrylate-based gels, illustrating the universality of the presented method, and its potential use in the above-mentioned applications.Graphical

Formulation and Evaluation of Quetiapine Loaded Pressure Sensitive Adhesive Patch for Transdermal Drug Delivery

The present research work was intended to develop and characterize the transdermal adhesive patch of quetiapine using different types of acrylate, polyisobutylene and silicon adhesives. Various permeation enhancers such as 1, 8 – cineole, D-limonene, Azone, IPM and Oleic acid were also evaluated to achieve desired permeation rate and hence to attain the improved bioavailability of quetiapine as compared to oral formulation. Formulations prepared were evaluated for physicochemical characterization, permeability enhancement potential by ex vivo, and stability studies. The results of the optimized formulation showed peel strength of 423 ± 4.13 cN/cm, flux of 54.92 ± 0.79 (µg/h/cm2) and % drug content of 98.16 ± 0.43% which was stable up to six months in accelerated condition. The results of the study revealed that the developed transdermal patch of quetiapine can be a promising alternative which provides effective management of schizophrenia in terms of improved patient compliance and reduced dosage frequency.