Non-transdermal microneedles for advanced drug delivery.
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ABSTRACT:
SUBMITTER: Lee K
PROVIDER: S-EPMC7295684 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The dissolving microneedle (DMN) patch is a transdermal delivery system, containing arrays of micro-sized polymeric needles capable of encapsulating therapeutic drugs within their matrix and releasing them into the skin. However, the elastic properties of the skin prevent DMNs from complete insertion and accurate delivery of encapsulated compounds into the skin. Moreover, the adhesive materials used in patches may cause skin irritation, inflammation, and redness. Therefore, we developed a patchless, micro-pillar integrated DMN (P-DMN) that is simple to fabricate and enhances transdermal drug delivery compared with traditional DMN patches. The micro-pillars were made of polymethyl methacrylate at a height of 300 ?m and a base diameter of 500 ?m. To fabricate P-DMNs, we employed hyaluronic acid, which is a widely used derma filler and plays a role in tissue re-epithelialization. We demonstrate that utilizing P-DMNs significantly improves the delivery efficiency of an encapsulated drug surrogate (91.83% ± 7.75%) compared with traditional DMNs (64.86% ± 8.17%). Interestingly, P-DMNs remarkably increase the skin penetration accuracy rate of encapsulated drugs, up to 97.78% ± 2.22%, compared with 44.44% ± 7.85% in traditional DMNs. Our findings suggest that P-DMNs could serve as a highly accurate and efficient platform for transdermal delivery of various types of micro- and macro-biomolecules.
| S-EPMC6724014 | biostudies-literature
Project description:Microneedles have attracted increasing interest among various medical fields due to their painless, noninvasive, and efficient way of drug delivery. However, practical applications of these microneedles in different epidermal locations and environments are still restricted by their low adhesion and poor antimicrobial activity. Here, inspired by the antibacterial strategy of Paenibacillus polymyxa and adhesion mechanisms of mussel byssi and octopus tentacles, we develop hierarchical microneedles with multifunctional adhesive and antibacterial abilities. With polydopamine hydrogel as the microneedle base and a loop of suction-cup-structured concave chambers encircling each microneedle, the generated microneedles can fit the skin well; keep strong adhesion in dry, moist, and wet environments; and realize self-repair after being split into two parts. Besides, as polymyxin is loaded into both the hydrogel tips and the polydopamine base, the microneedles are endowed with excellent ability to resist common bacteria during storage and usage. We have demonstrated that these microneedles not only showed excellent adhesion when applied to knuckles and ideal antibacterial activity but also performed well in drug-sustained release and treatment for the osteoarthritis rat model. These results indicate that bioinspired multifunctional microneedles will break through the limitation of traditional methods and be ideal candidates for versatile transdermal drug delivery systems.
| S-EPMC7231261 | biostudies-literature
Project description:Drug loaded dissolving microneedles (DMNs) fabricated with water soluble polymers have received increasing attentions as a safe and efficient transdermal drug delivery system. Usually, to reach a high drug delivery efficiency, an ideal drug distribution is gathering more drugs in the tip or the top part of DMNs. In this work, we introduce an easy and new method to introduce a bubble with controlled size into the body of DMNs. The introduction of bubbles can prevent the drug diffusion into the whole body of the MNs. The heights of the bubbles are well controlled from 75??m to 400??m just by changing the mass concentrations of polymer casting solution from 30?wt% to 10?wt%. The drug-loaded bubble MNs show reliable mechanical properties and successful insertion into the skins. For the MNs prepared from 15?wt% PVA solution, bubble MNs achieve over 80% of drug delivery efficiency in 20?seconds, which is only 10% for the traditional solid MNs. Additionally, the bubble microstructures in the MNs are also demonstrated to be consistent and identical regardless the extension of MN arrays. These scalable bubble MNs may be a promising carrier for the transdermal delivery of various pharmaceuticals.
| S-EPMC5144082 | biostudies-other
Project description:The intrinsic properties of therapeutic proteins generally present a major impediment for transdermal delivery, including their relatively large molecule size and susceptibility to degradation. One solution is to utilize microneedles (MNs), which are capable of painlessly traversing the stratum corneum and directly translocating protein drugs into the systematic circulation. MNs can be designed to incorporate appropriate structural materials as well as therapeutics or formulations with tailored physicochemical properties. This platform technique has been applied to deliver drugs both locally and systemically in applications ranging from vaccination to diabetes and cancer therapy. This review surveys the current design and use of polymeric MNs for transdermal protein delivery. The clinical potential and future translation of MNs are also discussed.
| S-EPMC6020694 | biostudies-literature
Project description:Collagen makes up a large proportion of the human body, particularly the skin. As the body ages, collagen content decreases, resulting in wrinkled skin and decreased wound healing capabilities. This paper presents a method of delivering type I collagen into porcine and human skin utilizing a polyvinylpyrrolidone microneedle delivery system. The microneedle patches were made with concentrations of 1, 2, 4, and 8% type I collagen (w/w). Microneedle structures and the distribution of collagen were characterized using scanning electron microscopy and confocal microscopy. Patches were then applied on the porcine and human skin, and their effectiveness was examined using fluorescence microscopy. The results illustrate that this microneedle delivery system is effective in delivering collagen I into the epidermis and dermis of porcine and human skin. Since the technique presented in this paper is quick, safe, effective and easy, it can be considered as a new collagen delivery method for cosmetic and therapeutic applications.
| S-EPMC5373921 | biostudies-literature
Project description:Polymer-based microneedles have drawn much attention in transdermal drug delivery resulting from their flexibility and biocompatibility. Traditional fabrication approaches are usually time-consuming and expensive. In this study, we developed a new double drawing lithography technology to make biocompatible SU-8 microneedles for transdermal drug delivery applications. These microneedles are strong enough to stand force from both vertical direction and planar direction during penetration. They can be used to penetrate into the skin easily and deliver drugs to the tissues under it. By controlling the delivery speed lower than 2 μl/min per single microneedle, the delivery rate can be as high as 71%.
| S-EPMC3869848 | biostudies-other
Project description:Microneedles are regarded as an emerging and promising transdermal drug delivery strategy. Great efforts are devoted to getting rid of their material restrictions and imparting them with abilities to carry various drugs. Here, inspired by ice formation in nature and based on characteristics of different frozen materials, the authors present novel ice microneedles made from versatile soft materials using a simple freezing template-based fabrication stratagem for effective transdermal delivery of diverse actives. Their strategy can convert microneedles with almost all water-containing components from softness into hardness for guaranteeing satisfactory penetration, thus removing their material component limitations. As all fabrication procedures are mild and actives can maintain activity during these processes, the ice microneedles can carry and deliver various actives from small molecules and macromolecules to even living organisms. They have demonstrated that these ice microneedles can easily penetrate mouse and swine skins using a microneedle injector, with their active-carried tips left inside after their ice base melts. Thus, by loading heparin, erythropoietin, or biosafe Bacillus subtilis (B. subtilis) inside the ice microneedles to treat mouse models, the practical values of these microneedles are well displayed, indicating their bright prospects in universal drug delivery systems.
| S-EPMC8425882 | biostudies-literature
Project description:IntroductionChronic kidney disease (CKD) affects approximately 13% of the world's population and will lead to dialysis or kidney transplantation. Unfortunately, clinically available drugs for CKD show limited efficacy and toxic extrarenal side effects. Hence, there is a need to develop targeted delivery systems with enhanced kidney specificity that can also be combined with a patient-compliant administration route for such patients that need extended treatment. Towards this goal, kidney-targeted nanoparticles administered through transdermal microneedles (KNP/MN) is explored in this study.MethodsA KNP/MN patch was developed by incorporating folate-conjugated micelle nanoparticles into polyvinyl alcohol MN patches. Rhodamine B (RhB) was encapsulated into KNP as a model drug and evaluated for biocompatibility and binding with human renal epithelial cells. For MN, skin penetration efficiency was assessed using a Parafilm model, and penetration was imaged via scanning electron microscopy. In vivo, KNP/MN patches were applied on the backs of C57BL/6 wild type mice and biodistribution, organ morphology, and kidney function assessed.ResultsKNP showed high biocompatibility and folate-dependent binding in vitro, validating KNP's targeting to folate receptors in vitro. Upon transdermal administration in vivo, KNP/MN patches dissolved within 30 min. At varying time points up to 48 h post-KNP/MN administration, higher accumulation of KNP was found in kidneys compared with MN that consisted of the non-targeting, control-NP. Histological evaluation demonstrated no signs of tissue damage, and kidney function markers, serum blood urea nitrogen and urine creatinine, were found to be within normal ranges, indicating preservation of kidney health.ConclusionsOur studies show potential of KNP/MN patches as a non-invasive, self-administrable platform to direct therapies to the kidneys.
| S-EPMC7596160 | biostudies-literature
Project description:In this study, for the first time, we have reported a sustained transdermal drug delivery from thermoresponsive poloxamer depots formed within the skin micropores following microneedle (MN) application. Firstly, we have investigated the sol-gel phase transition characteristics of poloxamers (PF®127, P108, and P87) at physiological conditions. Rheological measurements were evaluated to confirm the critical gelation temperature (CGT) of the poloxamer formulations with or without fluorescein sodium (FS), as a model drug, at various concentrations. Optimized poloxamer formulations were subjected to in vitro release studies using a vial method. Secondly, polymeric MNs were fabricated using laser-engineered silicone micromolds from various biocompatible polymeric blends of Gantrez S-97, PEG 10000, PEG200, PVP K32, and PVP K90. The MN arrays were characterized for mechanical strength, insertion force determination, in situ dissolution kinetics, moisture content, and penetration depth. The optimized MN arrays with good mechanical strength and non-soluble nature were used to create micropores in the neonatal porcine skin. Microporation in neonatal porcine skin was confirmed by dye-binding study, skin integrity assessment, and histology study. Finally, the in vitro delivery of FS from optimized poloxamer formulations was conducted across non-porated vs microporated skin samples using vertical Franz diffusion cells. Results concluded that permeation of FS was sustained for 96 h across the MN-treated skin samples containing in situ forming depot poloxamer formulations compared to non-microporated skin which sustained the FS delivery for 72 h. Confocal microscopic images confirmed the distribution of higher florescence intensity of FS in skin tissues after permeation study in case of MN-treated skin samples vs intact skin samples.
| S-EPMC6606675 | biostudies-literature
Project description:Because carbon is the basic element of all life forms and has been successfully applied as a material for medical applications, it is desirable to investigate carbon for drug delivery applications, as well. In this work, we report the fabrication of a hollow carbon microneedle array with flow channels using a conventional carbon-microelectromechanical system (C-MEMS) process. This process utilizes the scalable and irreversible step of pyrolysis, where prepatterned SU-8 microneedles (precursor) are converted to glassy carbon structures in an inert atmosphere at high temperature (900 °C) while retaining their original shape upon shrinkage. Once converted to glassy carbon, the microneedles inherit the unique properties of hardness, biocompatibility, and thermal and chemical resistance associated with this material. A comparative study of hardness and Young's modulus for carbon microneedles and SU-8 microneedles was performed to evaluate the increased strength of the microneedles induced by the C-MEMS process steps. Structural shrinkage of the carbon microneedles upon pyrolysis was observed and estimated. Material characterizations including energy-dispersive X-ray spectroscopy (EDX) and Raman spectroscopy were carried out to estimate the atomic percentage of carbon in the microneedle structure and its crystalline nature, respectively. Our investigations confirm that the microneedles are glassy in nature. Compression and bending tests were also performed to determine the maximum forces that the carbon microneedles can withstand, and it was found that these forces were approximately two orders of magnitude higher than the resistive forces presented by skin. A microneedle array was inserted into mouse skin multiple times and was successfully removed without the breakage of any microneedles.
| S-EPMC6295442 | biostudies-literature