Polymeric Microneedle Drug Delivery Systems: Mechanisms of Treatment, Material Properties, and Clinical Applications—A Comprehensive Review
Abstract
:1. Introduction
2. Polymeric Microneedle Drug Delivery Systems
2.1. Substrate Materials for Polymeric Microneedle Preparation
Material | Hardness | Modulus of Elasticity (Gpa) | Tensile Strength (MPa) | Elongation at Break (%) | Stability | Dissolution Rate | Biocompatibility | Used Routes |
---|---|---|---|---|---|---|---|---|
PLGA | Strong enough to penetrate skin | 1–3 | 50–100 | 50–200 | At temperatures above 100 °C, it converts to the glassy phase [29] | Slow degradation over days to months [30] | Compatible with PMM, CD | Preparation of degradable microneedles for drug release [31] |
PVP | Strong enough to penetrate skin, blended with other polymers to optimize performance, e.g., copolymer PVP-MAA with 1% MAA doubles the mechanical strength of pure PVP microneedles; 25% MAA increases the mechanical strength up to four times [18] | 0.5–1.5 | 30–60 | 100–300 | Melts at 50 °C [32] | Dissolves within 1 min of insertion into skin [33] | Compatible with MAA, PVA [18] | Preparation of soluble microneedles for drug delivery [34] |
PVA | Blending with PVP improves hardness | 1–2 | 40–80 | 50–150 | Prevents denaturation of encapsulated drugs by heating and freezing [20] | PVA needles are microcrystalline cross-linked, do not dissolve in the dermis, and can be withdrawn intact after release [35] | Weak interaction between PVP and PVA [19] | Enhanced mechanical strength of microneedles as a coating material [36] |
PCL | Modification of PCL with gelatin embedding technology increases mechanical strength by up to two times | 0.5–2 | 20–50 | 50–250 | Melting point of 60 °C, glass transition temperature of −60 °C [37] | Microneedle tip remains in the skin 1 h after insertion [14] | PVA/PVP patches are biocompatible with PCL and act as a support array [38] | Preparation of pharmaceutical coatings for non-heat-resistant drugs [39] |
HA | Strong enough to penetrate skin | 0.1–0.5 | 10–30 | 800–1200 | Prevents denaturation of encapsulated drugs by heating and freezing [20] | Penetrates into isolated human skin epidermis and dissolves within 10 min of insertion of tip [40] | Forms PEEK/HA composites with PEEK-based filaments, compatible with most materials [41] | Preparation of soluble microneedles for transdermal drug delivery [42] |
PLA | High hardness at 39 °C | 3–4 | 40–60 | 4–10 | Aging at 39 °C, high stability performance [43] | The degradation rate is constant at 25 μm/h under alkaline conditions [44] | Compatible with PMM, CD | Preparation of soluble microneedles for drug delivery [43] |
2.2. Properties of Polymer Microneedle Systems
3. Skin Tissue Properties at the Site of Stimulation Mediate Microneedle Action
3.1. Transdermal Drug Delivery: Subcutaneous Microcirculatory Oscillations Promote Drug Absorption
3.2. Microneedle Drug Delivery: Acupoint–Target Organ Ganglion Connection Promotes Drug Target Accumulation
4. Application of the Polymeric Microneedle Drug Delivery Systems
4.1. Diabetes
4.2. Oncology
4.3. Pain
4.4. Rheumatoid Arthritis
4.5. Vaccine Delivery
5. Outlook and Conclusions
5.1. Possible Prospective Strategies for Optimizing Stimulation Sites
5.2. Prospects for New Biocompatible Materials with Superior Mechanical Properties
5.3. Consideration of Safety Strategies to Increase Microneedle Drug Loading
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Research Topics | Patent Number | Instrument Description | Application Scenarios/Material Properties |
---|---|---|---|
Microneedle and manufacturing method | US2021290829A1 [119] | A microneedle or microneedle device includes a microneedle body, extending from a base to a penetrating tip formed from a silk fibroin-based material, which is easy to fabricate and highly biocompatible. The silk fibroin microneedles can be fully or partially biodegradable and/or bioerodible. The silk fibroin is highly stable, affords room temperature storage, and is implantable. The silk fibroin structure can be modulated to control the rate of active agent delivery. | Since silk fibroin microneedles are prepared under mild conditions, the stabilizing effect of silk fibroin on incorporated active agents, such as proteins, can be combined with the convenience and self-administration of microneedles to produce drug delivery platforms that are safe and easy to self-administer and can be stored at elevated temperatures. The microneedles can carry antibiotics for the treatment of local infections. |
US20180064920A1 [113] | The invention generally relates to microneedle devices, methods of making them, pharmaceutical compositions comprising them, and methods of treating a disease by administering them. Specifically, the disclosed microneedle devices comprise a plurality of biocompatible microneedles having one or more of the following: (i) a curved, discontinuous, undercut, and/or perforated sidewall; (ii) a sidewall comprising a breakable support; and (iii) a cross-section that is non-circular and non-polygonal. Alternatively, the microneedles may be tiered. This article is intended as a scanning tool with the purpose of searching within the particular art and is not intended to limit the scope of the present invention. | Through a sidewall comprising a breakable support and a cross-section that is non-circular and non-polygonal, this kind of microneedle can be used for the delivery of insulin and vaccines, as well as the delivery of various enzymes and growth hormones, and it can be used to treat autoimmune diseases by providing immunomodulators. Microneedling can also be used to diagnose a variety of conditions, such as diabetes, heart attacks, infectious and bacterial infections, or to perform standard blood tests. | |
US8414548B2 [120] | The microneedle array device includes a substantially planar substrate having an array of apertures, as well as a plurality of microneedles projecting at an angle from the planar substrate. The microneedles have a base portion integrally connected to the substrate, a tip end portion distal to the base portion, and a body portion in between. Each microneedle has at least one channel extending substantially from the base portion through at least a part of the body portion. The channel is open along at least part of the body portion and is in fluid communication with at least one of the apertures in the substrate. | The microneedles have a basic rectangular cross-sectional shape with a tapered tip and are composed of biocompatible metallic materials. This special structure not only reduces the biological barrier of the skin but also improves the delivery rate of the drug. This structure allows the device to deliver a wider variety of vaccines, as well as other drugs. | |
JP7291087B2 [121] | Microneedle arrays are provided to administer medications or other substances into tissue. A method for fabricating an array of microneedles is also provided. The array includes a base substrate, a primary funnel extending from one of the base substrates, two or more medium microneedles extending from the primary funnel portion, and two or more microneedles comprising the desired material. This method provides a non-porous and gas-permeable type, with two or more cavities defining each microneedle; filling the cavity with a fluid material containing the object and liquid vehicle; and removing at least a portion of the liquid vehicle to form multiple microneedles that contain the desired material, including drying the fluid material. The filling is carried out by applying the pressure difference between opposed surfaces of the type. | In microneedle drug delivery embodiments, the substance of interest may be a prophylactic, therapeutic or diagnostic agent useful in medical or veterinary applications; prophylactic or therapeutic substances, referred to herein as APIs, may include representative APIs for administration, such as antibiotics, antivirals, analgesics, antihistamines, anti-inflammatories, anticoagulants, allergens, vitamins, and anti-tumor agents.Microneedle transdermal drug delivery substances include vaccines, such as infectious disease vaccines, cancer treatment vaccines, neurological disease vaccines, allergy vaccines, smoking cessation vaccines, or other addiction vaccines. Examples include anthrax, cervical cancer, dengue, diphtheria, Ebola, hepatitis A, HIV/AIDS, human papillomavirus (HPV). | |
Microneedle delivery device and method | US9549746B2 [122] | A microprotrusion array for transporting a material across a biological barrier, wherein said array comprises a plurality of microprotusions composed of a swellable polymer composition. | These microneedles, comprising a plurality of microprotusions made from a swellable polymer composition, are used for the delivery of beneficial substances across or into the skin or for the monitoring of levels of substances of diagnostic interest in the body. |
US10953210B2 [123] | A drug delivery device that delivers pharmacologically active substances transdermally using microneedles arranged on a belt mounted rotatably about a plurality of rollers, the microneedles having an associated drug reservoir mounted on the belt that is compressed when the needles and belt are brought into contact with the skin. | The microneedles can consist of various suitable materials, such as silicone, stainless steel, and plastic. The microneedle allows a defined amount of drug to be pumped almost simultaneously through the microneedle holes to a defined depth within the skin. The device ensures that the needle is in good contact with the skin at the point of administration and prevents drug reflux by actively forcing the drug through the microneedle holes into the skin. | |
US10716764B2 [124] | The invention concerns a transdermal delivery system for controlled dispensing of an active substance to and through a porous surface. A certain amount of fluid comprising at least one active substance and at least one solvent is dispensed into an administration reservoir. In the administration reservoir at least one solvent is separated from the administration reservoir by a solvent recovery method, allowing the active substance to achieve a certain level on an interface device that is permeable for that active substance. Thus, the active substance is absorbable via diffusion from the interface device through a porous surface to be treated. | Active ingredients which can be administered via the devices of the present invention include pharmaceutical compositions that are capable of transdermal administration. Agents include those which are sufficiently lipophilic or hydrophilic to penetrate the surface of the skin and the stratum corneum. Some of these agents can reach the micro vessels of the skin and are subsequently absorbed and distributed throughout the body. Drugs suitable for transdermal delivery include scopolamine, nitrates such as nitroglycerin, antihypertensive or antiadrenergic drugs such as clonidine, 17-beta-estradiol, and testosterone. In addition to transdermal delivery, the disclosed dispensers can also be used for the topical surface application of drugs such as antibiotics, corticosteroids, minoxidil, or retinoids (e.g., retinol A). | |
US20220040466A1 [125] | A medical system. The medical system includes at least one compartment for a fluid, a fluid path, and at least one microneedle fluidly connected to at least one compartment by the fluid path. A medical infusion system is also disclosed. The system includes a wearable housing, at least one non-pressurized compartment for a fluid contained within the housing, at least one fluid path fluidly connected to the at least one compartment, and at least one microneedle fluidly connected to the at least one compartment by the fluid path, wherein the fluid path extends through the microneedle. | This microneedle can be incorporated as a fluid delivery device for administering fluids such as insulin, chemotherapies, vitamins, painkillers, antibacterials, antimicrobials, or any other therapeutic or nutritive fluid or compound therapy. |
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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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Liu, Y.; Mao, R.; Han, S.; Yu, Z.; Xu, B.; Xu, T. Polymeric Microneedle Drug Delivery Systems: Mechanisms of Treatment, Material Properties, and Clinical Applications—A Comprehensive Review. Polymers 2024, 16, 2568. https://doi.org/10.3390/polym16182568
Liu Y, Mao R, Han S, Yu Z, Xu B, Xu T. Polymeric Microneedle Drug Delivery Systems: Mechanisms of Treatment, Material Properties, and Clinical Applications—A Comprehensive Review. Polymers. 2024; 16(18):2568. https://doi.org/10.3390/polym16182568
Chicago/Turabian StyleLiu, Yun, Ruiyue Mao, Shijia Han, Zhi Yu, Bin Xu, and Tiancheng Xu. 2024. "Polymeric Microneedle Drug Delivery Systems: Mechanisms of Treatment, Material Properties, and Clinical Applications—A Comprehensive Review" Polymers 16, no. 18: 2568. https://doi.org/10.3390/polym16182568