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International Journal of Pharmaceutics Sep 2020Transdermal drug delivery using microneedles is increasingly gaining interest due to the issues associated with oral drug delivery routes. Gastrointestinal route exposes... (Review)
Review
Transdermal drug delivery using microneedles is increasingly gaining interest due to the issues associated with oral drug delivery routes. Gastrointestinal route exposes the drug to acid and enzymes present in the stomach, leading to denaturation of the compound and resulting in poor bioavailability. Microneedle transdermal drug delivery addresses the problems linked to oral delivery and to relieves the discomfort of patients associated with injections to increase patient compliance. Microneedles can be broadly classified into five types: solid microneedles, coated microneedles, dissolving microneedles, hollow microneedles, and hydrogel-forming microneedles. The materials used for the preparation of microneedles dictate the different applications and features present in the microneedle. Polymeric microneedle arrays present an improved method for transdermal administration of drugs as they penetrate the skin stratum corneum barrier with minimal invasiveness. The review summarizes the importance of polymeric microneedle and discussed some of the most important therapeutic drugs in research, mainly protein drugs, vaccines and small molecule drugs in regenerative medicine.
Topics: Administration, Cutaneous; Drug Delivery Systems; Humans; Microinjections; Needles; Pharmaceutical Preparations; Polymers; Skin
PubMed: 32739388
DOI: 10.1016/j.ijpharm.2020.119673 -
Journal of Controlled Release :... Aug 2022Microneedles are a rapidly developing method for the transdermal delivery of therapeutic compounds. All types of microneedles, whether solid, hollow, coated, or... (Review)
Review
Microneedles are a rapidly developing method for the transdermal delivery of therapeutic compounds. All types of microneedles, whether solid, hollow, coated, or dissolving function by penetrating the stratum corneum layer of the skin producing a microchannel through which therapeutic agents may be delivered. To date, coated and hollow microneedles have been the most successful, despite suffering from issues such as poor drug loading capabilities and blocked pores. Dissolving microneedles, on the other hand, have superior drug loading as well as other positive attributes that make it an ideal delivery system, including simple methods of fabrication and disposal, and abundantly available materials. Indeed, dissolvable microneedles can even be fabricated entirely from the therapeutic agent itself thus eliminating the requirement for additional excipients. This focused review presents the recent developments and trends of dissolving microneedles as well as potential future directions. The advantages, and disadvantages of dissolving microneedles as well as fabrication materials and methods are discussed. The potential applications of dissolving microneedles as a drug delivery system in different therapeutic areas in both research literature and clinical trials is highlighted. Applications including the delivery of cosmetics, vaccine delivery, diagnosis and monitoring, cancer, pain and inflammation, diabetes, hair and scalp disorders and inflammatory skin diseases are presented. The current trends observed in the microneedle landscape with particular emphasis on contemporary clinical trials and commercial successes as well as barriers impeding microneedle development and commercialisation are also discussed.
Topics: Administration, Cutaneous; Drug Delivery Systems; Microinjections; Needles; Pharmaceutical Preparations; Skin; Skin Absorption
PubMed: 35662577
DOI: 10.1016/j.jconrel.2022.05.045 -
Advanced Drug Delivery Reviews Jan 2019Insulin therapy is necessary to regulate blood glucose levels for people with type 1 diabetes and commonly used in advanced type 2 diabetes. Although subcutaneous... (Review)
Review
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.
Topics: Administration, Cutaneous; Animals; Electroporation; Humans; Hypoglycemic Agents; Insulin; Iontophoresis; Microinjections; Needles; Ultrasonic Waves
PubMed: 30528729
DOI: 10.1016/j.addr.2018.12.006 -
Biomedicine & Pharmacotherapy =... Jan 2019The most widely used methods for transdermal administration of the drugs are hypodermic needles, topical creams, and transdermal patches. The effect of most of the... (Review)
Review
The most widely used methods for transdermal administration of the drugs are hypodermic needles, topical creams, and transdermal patches. The effect of most of the therapeutic agents is limited due to the stratum corneum layer of the skin, which serves as a barrier for the molecules and thus only a few molecules are able to reach the site of action. A new form of delivery system called the microneedles helps to enhance the delivery of the drug through this route and overcoming the various problems associated with the conventional formulations. The primary principle involves disruption of the skin layer, thus creating micron size pathways that lead the drug directly to the epidermis or upper dermis region from where the drug can directly go into the systemic circulation without facing the barrier. This review describes the various potential and applications of the microneedles. The various types of microneedles can be fabricated like solid, dissolving, hydrogel, coated and hollow microneedles. Fabrication method selected depends on the type and material of the microneedle. This system has increased its application to many fields like oligonucleotide delivery, vaccine delivery, insulin delivery, and even in cosmetics. In recent years, many microneedle products are coming into the market. Although a lot of research needs to be done to overcome the various challenges before the microneedles can successfully launch into the market.
Topics: Administration, Cutaneous; Animals; Drug Delivery Systems; Epidermis; Humans; Microinjections; Needles
PubMed: 30551375
DOI: 10.1016/j.biopha.2018.10.078 -
Drug Delivery and Translational Research Feb 2022
Topics: Drug Delivery Systems; Microinjections; Needles
PubMed: 34932196
DOI: 10.1007/s13346-021-01100-7 -
Advanced Science (Weinheim,... Feb 2024Microneedles have emerged as a promising platform for transdermal drug delivery with prominent advantages, such as enhanced permeability, mitigated pain, and improved... (Review)
Review
Microneedles have emerged as a promising platform for transdermal drug delivery with prominent advantages, such as enhanced permeability, mitigated pain, and improved patient adherence. While microneedles have primarily been employed for delivering small molecules, nucleic acids, peptides, and proteins, recent researches have demonstrated their prospect in combination with cell therapy. Cell therapy involving administration or transplantation of living cells (e.g. T cells, stem cells, and pancreatic cells) has gained significant attention in preclinical and clinical applications for various disease treatments. However, the effectiveness of systemic cell delivery may be restricted in localized conditions like solid tumors and skin disorders due to limited penetration and accumulation into the lesions. In this perspective, an overview of recent advances in microneedle-assisted cell delivery for immunotherapy, tissue regeneration, and hormone modulation, with respect to their mechanical property, cell loading capacity, as well as viability and bioactivity of the loaded cells is provided. Potential challenges and future perspectives with microneedle-mediated cell therapy are also discussed.
Topics: Humans; Administration, Cutaneous; Drug Delivery Systems; Microinjections; Needles; Proteins
PubMed: 37899686
DOI: 10.1002/advs.202304124 -
BMC Biotechnology Jan 2016The CRISPR/Cas9 system is increasingly used for gene inactivation in mouse zygotes, but homology-directed mutagenesis and use of inbred embryos are less established. In...
BACKGROUND
The CRISPR/Cas9 system is increasingly used for gene inactivation in mouse zygotes, but homology-directed mutagenesis and use of inbred embryos are less established. In particular, Rosa26 knock-in alleles for the insertion of transgenes in a genomic 'safe harbor' site, have not been produced. Here we applied CRISPR/Cas9 for the knock-in of 8-11 kb inserts into Rosa26 of C57BL/6 zygotes.
RESULTS
We found that 10-20 % of live pups derived from microinjected zygotes were founder mutants, without apparent off-target effects, and up to 50 % knock-in embryos were recovered upon coinjection of Cas9 mRNA and protein. Using this approach, we established a new mouse line for the Cre/loxP-dependent expression of Cas9.
CONCLUSIONS
Altogether, our protocols and resources support the fast and direct generation of new Rosa26 knock-in alleles and of Cas9-mediated in vivo gene editing in the widely used C57BL/6 inbred strain.
Topics: Animals; CRISPR-Cas Systems; Cloning, Molecular; Embryo, Mammalian; Gene Knock-In Techniques; Mice; Mice, Inbred C57BL; Microinjections; RNA, Untranslated
PubMed: 26772810
DOI: 10.1186/s12896-016-0234-4 -
Nature Nanotechnology Jul 2015Seamless and minimally invasive three-dimensional interpenetration of electronics within artificial or natural structures could allow for continuous monitoring and...
Seamless and minimally invasive three-dimensional interpenetration of electronics within artificial or natural structures could allow for continuous monitoring and manipulation of their properties. Flexible electronics provide a means for conforming electronics to non-planar surfaces, yet targeted delivery of flexible electronics to internal regions remains difficult. Here, we overcome this challenge by demonstrating the syringe injection (and subsequent unfolding) of sub-micrometre-thick, centimetre-scale macroporous mesh electronics through needles with a diameter as small as 100 μm. Our results show that electronic components can be injected into man-made and biological cavities, as well as dense gels and tissue, with >90% device yield. We demonstrate several applications of syringe-injectable electronics as a general approach for interpenetrating flexible electronics with three-dimensional structures, including (1) monitoring internal mechanical strains in polymer cavities, (2) tight integration and low chronic immunoreactivity with several distinct regions of the brain, and (3) in vivo multiplexed neural recording. Moreover, syringe injection enables the delivery of flexible electronics through a rigid shell, the delivery of large-volume flexible electronics that can fill internal cavities, and co-injection of electronics with other materials into host structures, opening up unique applications for flexible electronics.
Topics: Animals; Electroencephalography; Electronics, Medical; Equipment Design; Equipment Failure Analysis; Mice; Microinjections; Nanotechnology; Prosthesis Implantation; Syringes; Transducers
PubMed: 26053995
DOI: 10.1038/nnano.2015.115 -
Biomedical Microdevices Jun 2023The microneedles have attracted great interests for a wide range of transdermal biomedical applications, such as biosensing and drug delivery, due to the advantages of... (Review)
Review
The microneedles have attracted great interests for a wide range of transdermal biomedical applications, such as biosensing and drug delivery, due to the advantages of being painless, semi-invasive, and sustainable. The ongoing challenges are the materials and fabrication methods of the microneedles in order to obtain a specific shape, configuration and function of the microneedles to achieve a target biomedical application. Here, this review would introduce the types of materials of the microneedles firstly. The hardness, Young's modulus, geometric structure, processability, biocompatibility and degradability of the microneedles are explored as well. Then, the fabrication methods for the solid and hollow microneedles in recent years are reviewed in detail, and the advantages and disadvantages of each process are analyzed and compared. Finally, the biomedical applications of the microneedles are reviewed, including biosensing, drug delivery, body fluid extraction, and nerve stimulation. It is expected that this work provides the fundamental knowledge for developing new microneedle devices, as well as the applications in a variety of biomedical fields.
Topics: Administration, Cutaneous; Drug Delivery Systems; Needles; Elastic Modulus; Microinjections
PubMed: 37278852
DOI: 10.1007/s10544-023-00658-y -
Molecules (Basel, Switzerland) Sep 2021A microneedle (MN) is a painless and minimally invasive drug delivery device initially developed in 1976. As microneedle technology evolves, microneedles with different... (Review)
Review
A microneedle (MN) is a painless and minimally invasive drug delivery device initially developed in 1976. As microneedle technology evolves, microneedles with different shapes (cone and pyramid) and forms (solid, drug-coated, hollow, dissolvable and hydrogel-based microneedles) have been developed. The main objective of this review is the applications of microneedles in biomedical areas. Firstly, the classifications and manufacturing of microneedle are briefly introduced so that we can learn the advantages and fabrications of different MNs. Secondly, research of microneedles in biomedical therapy such as drug delivery systems, diagnoses of disease, as well as wound repair and cancer therapy are overviewed. Finally, the safety and the vision of the future of MNs are discussed.
Topics: Animals; Drug Delivery Systems; Humans; Microinjections; Needles; Pharmaceutical Preparations
PubMed: 34641460
DOI: 10.3390/molecules26195912