Recent advances in microneedles-mediated transdermal delivery of protein and peptide drugs.
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ABSTRACT:
SUBMITTER: Liu T
PROVIDER: S-EPMC8424228 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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:Microneedles (MNs) have been used to deliver drugs for over two decades. These platforms have been proven to increase transdermal drug delivery efficiency dramatically by penetrating restrictive tissue barriers in a minimally invasive manner. While much of the early development of MNs focused on transdermal drug delivery, this technology can be applied to a variety of other non-transdermal biomedical applications. Several variations, such as multi-layer or hollow MNs, have been developed to cater to the needs of specific applications. The heterogeneity in the design of MNs has demanded similar variety in their fabrication methods; the most common methods include micromolding and drawing lithography. Numerous materials have been explored for MN fabrication which range from biocompatible ceramics and metals to natural and synthetic biodegradable polymers. Recent advances in MN engineering have diversified MNs to include unique shapes, materials, and mechanical properties that can be tailored for organ-specific applications. In this review, we discuss the design and creation of modern MNs that aim to surpass the biological barriers of non-transdermal drug delivery in ocular, vascular, oral, and mucosal tissue.
| S-EPMC7295684 | 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:Drug delivery through the skin by transdermal patches has a long history. Subsequent growth of transdermal science proved prominent utility of transdermal systems meant for passive diffusion of the drug. It was followed by the development of iontophoresis- and sonophoresis-based transdermal delivery systems. Microneedle array has now caught attention of the investigators owing to its immense utility in transdermal delivery of very large molecules with ionic and hydrophilic nature. In this technical note, we present the current scenario, applications, and recent advances in microneedle array-based delivery of the most critical molecules through the skin. The application of microneedle has widely been investigated, and these technologies are being developed for the delivery of bio-therapeutics, bio-macromolecules, insulin, growth hormones, immunobiologicals, proteins, siRNA, and peptides. Potential of microneedles to transform the global transdermal market is highlighted in terms of the success rate of the microneedle technologies in clinical trials reaching to the global market. The arrival of the commercial microneedle-based products in the market is highly anticipated as they have potential to portray remarkable impact on clinical medicine in near future.
| S-EPMC7276250 | biostudies-literature
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:Insulin therapy is necessary to regulate blood glucose levels for people with type 1 diabetes and commonly used in advanced type 2 diabetes. Although subcutaneous insulin administration via hypodermic injection or pump-mediated infusion is the standard route of insulin delivery, it may be associated with pain, needle phobia, and decreased adherence, as well as the risk of infection. Therefore, transdermal insulin delivery has been widely investigated as an attractive alternative to subcutaneous approaches for diabetes management in recent years. Transdermal systems designed to prevent insulin degradation and offer controlled, sustained release of insulin may be desirable for patients and lead to increased adherence and glycemic outcomes. A challenge for transdermal insulin delivery is the inefficient passive insulin absorption through the skin due to the large molecular weight of the protein drug. In this review, we focus on the different transdermal insulin delivery techniques and their respective advantages and limitations, including chemical enhancers-promoted, electrically enhanced, mechanical force-triggered, and microneedle-assisted methods.
| S-EPMC6556146 | biostudies-literature
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:The interest in safe and efficient transdermal drug delivery systems has been increasing in recent decades. In light of that, polymeric dissolving microneedles (DMNs) were developed as an ideal platform capable of delivering micro- and macro-biomolecules across the skin in a minimally invasive manner. A vast majority of studies, however, suggest that the shape of DMNs, as well as the elastic properties of skin, affects the delivery efficiency of materials encapsulated within DMNs. Likewise, in dynamic tissues, DMNs would easily distend from the skin, leading to inefficient delivery of encapsulated agents. Thus, herein, to improve delivery efficiency of DMN encapsulated agents, a novel hyaluronic acid backbone-based tissue interlocking DMN (TI-DMN) is developed. TI-DMN is simple to fabricate and significantly improves the transdermal delivery efficiency of encapsulated materials compared with traditional DMNs. The enhanced tissue interlocking feature of TI-DMN is achieved through its sharp tip, wide body, and narrow neck geometry. This paper demonstrates that TI-DMN would serve as an attractive transdermal delivery platform to enhance penetration and delivery efficiency of a wide range of biomolecules into the body.
| S-EPMC6536679 | biostudies-literature