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Journal of Drug Targeting Jan 2017Transdermal delivery using microneedles is gaining increasing attention from pharmaceutical and cosmetic companies as one of the promising drug delivery methods.... (Review)
Review
Transdermal delivery using microneedles is gaining increasing attention from pharmaceutical and cosmetic companies as one of the promising drug delivery methods. Microneedle products have recently become available on the market, and some of them are under evaluation for efficacy and safety. To be available in the market for cosmetic and therapeutic use, several factors should be considered, including pain, anxiety, convenience and safety. These factors are summarized and reviewed in this article according to type of microneedle. Various kinds of materials have been used for manufacturing microneedles and developing drug formulations for microneedles. Safety information about materials used for microneedles is summarized in terms of type of microneedles. In addition to their biocompatibility, mechanical safety is also discussed. This review can provide guidelines for designing microneedle products for proper use.
Topics: Administration, Cutaneous; Anxiety; Drug Delivery Systems; Equipment Design; Humans; Microinjections; Needles; Pain, Procedural; Patient Compliance; Pharmaceutical Preparations; Skin Absorption
PubMed: 27282644
DOI: 10.1080/1061186X.2016.1200589 -
The American Journal of Managed Care Nov 2022Standard ocular drug delivery methods generally are safe and effective for treating diseases of the eye. However, many routes of administration carry the risk of adverse... (Review)
Review
Standard ocular drug delivery methods generally are safe and effective for treating diseases of the eye. However, many routes of administration carry the risk of adverse effects due to drug exposure to anterior ocular tissues. Additionally, these delivery methods may not result in high and consistent levels of a therapeutic agent delivered to target tissues for diseases affecting the posterior segment of the eye. Injection into the suprachoroidal space (SCS) represents an alternative method of ocular drug delivery to the posterior segment. SCS injection facilitates targeted distribution to affected chorioretinal tissues for potential efficacy benefits, compartmentalization away from unaffected anterior segment tissues for potential safety benefits, and a high degree of bioavailability. Furthermore, the SCS may serve as a drug depot for long-acting drug delivery of small-molecule suspensions. Until recently, drug delivery to the SCS could be achieved only in the operating room setting with anesthetic immobilization of the eye and surgical dissection through the sclera. A novel microneedle device, the SCS Microinjector® (Clearside Biomedical, Inc) was developed to permit physicians to administer therapies safely and reliably into the SCS in the office setting. Successful use of SCS injection has been demonstrated with triamcinolone acetonide injectable suspension (Xipere®, Bausch + Lomb), a novel formulation optimized for use with the SCS Microinjector®. FDA approval of this combination drug and device for the treatment of macular edema associated with uveitis (UME) was based on outcomes from the phase 3 PEACHTREE study (NCT02595398); other important studies included its long-term observational extension (MAGNOLIA; NCT02952001) and an open-label safety study (AZALEA; NCT03097315). The SCS Microinjector® together with triamcinolone acetonide injectable suspension for use in the SCS presents an opportunity for safe and effective drug delivery for the treatment of UME and, potentially, for broader use with alternate medications to treat other ocular diseases that impact chorioretinal tissues (eg, age-related macular degeneration, diabetic retinopathy, choroidal melanoma).
Topics: Humans; Microinjections; Choroid; Triamcinolone Acetonide; Needles; Choroidal Effusions; Observational Studies as Topic
PubMed: 36395492
DOI: 10.37765/ajmc.2022.89270 -
Plastic and Reconstructive Surgery Jul 2024Functional recovery after acellular nerve allograft (ANA) reconstruction remains inferior to that after autologous nerve grafting, but improved outcomes have been... (Comparative Study)
Comparative Study
BACKGROUND
Functional recovery after acellular nerve allograft (ANA) reconstruction remains inferior to that after autologous nerve grafting, but improved outcomes have been demonstrated with the addition of adipose-derived mesenchymal stem cells (MSCs). Controversy exists regarding the optimal cell-delivery method to enhance ANA reconstructions. The authors investigated the functional recovery of ANAs after dynamic seeding versus microinjection of MSCs.
METHODS
Forty Lewis rats underwent reconstruction of a 10-mm sciatic nerve defect. Animals were divided into 4 groups: reversed autograft, ANA alone, dynamically seeded ANA, or ANA injected with MSCs. During the survival period, ultrasound measurements of the tibialis anterior muscle cross-sectional area were performed. At 12 weeks, functional recovery was evaluated using measurements of ankle contracture, compound muscle action potential, maximum isometric tetanic force, muscle mass, histomorphometry, and immunofluorescence.
RESULTS
The dynamic seeding and microinjection groups demonstrated higher cross-sectional tibialis anterior muscle area recovery than autografts and ANAs alone at week 8 and weeks 4 and 8, respectively. The ankle contracture and compound muscle action potential amplitude recovery were superior in autografts and both seeding methods compared with ANAs alone. The microinjection group demonstrated significantly higher isometric tetanic force, muscle mass, and number of axons compared with ANAs alone. Both seeding methods showed higher CD34 densities compared with ANAs alone. No significant differences between dynamic seeding and microinjection were observed in functional or histologic outcomes.
CONCLUSIONS
The addition of MSCs to ANAs demonstrated earlier motor regeneration compared with autografts and ANAs alone. Both seeding methods improved functional outcomes in the rat sciatic nerve defect model.
Topics: Animals; Mesenchymal Stem Cell Transplantation; Rats, Inbred Lew; Sciatic Nerve; Rats; Adipose Tissue; Microinjections; Nerve Regeneration; Allografts; Male; Recovery of Function; Disease Models, Animal; Mesenchymal Stem Cells
PubMed: 37537724
DOI: 10.1097/PRS.0000000000010970 -
Advanced Biosystems Jul 2019The advancement of cell injections has created a need for accurate, efficient, and low-invasive injections. However, the conventional approaches to reduce cell damage...
The advancement of cell injections has created a need for accurate, efficient, and low-invasive injections. However, the conventional approaches to reduce cell damage during penetration, mainly optimization of micropipette tips and vision-based automatic injections, have almost reached the limit. Here, described are the design and implementation of a robotic-aided rotatory microinjection system to reduce cell deformation and penetration force during the injection. The homocentric rotation technology integrates an ultraprecise manipulation system with multiple degrees of freedom, which tremendously diminishes the damage to the cell. Through systematic tests on zebrafish embryo microinjection, compared with traditional straightforward cell injection techniques, the rotary cell injection approach is able to reduce the penetration deformation and force of the specimen up to 30%. This work breaks the performance limit of current microinjection techniques, and paves a new way for the development of low-invasive cell injection systems. It is envisioned that this rotary microrobot system can excavate enormous applications in the field of biomedicine, such as artificial fertilization and gene therapy.
Topics: Animals; Genetic Therapy; Insemination, Artificial; Microinjections; Robotics; Zebrafish
PubMed: 32648674
DOI: 10.1002/adbi.201800274 -
Nature Protocols Jun 2018CRISPR/Cas9 technology has transformed mouse genome editing with unprecedented precision, efficiency, and ease; however, the current practice of microinjecting CRISPR... (Comparative Study)
Comparative Study
CRISPR/Cas9 technology has transformed mouse genome editing with unprecedented precision, efficiency, and ease; however, the current practice of microinjecting CRISPR reagents into pronuclear-stage embryos remains rate-limiting. We thus developed CRISPR ribonucleoprotein (RNP) electroporation of zygotes (CRISPR-EZ), an electroporation-based technology that outperforms pronuclear and cytoplasmic microinjection in efficiency, simplicity, cost, and throughput. In C57BL/6J and C57BL/6N mouse strains, CRISPR-EZ achieves 100% delivery of Cas9/single-guide RNA (sgRNA) RNPs, facilitating indel mutations (insertions or deletions), exon deletions, point mutations, and small insertions. In a side-by-side comparison in the high-throughput KnockOut Mouse Project (KOMP) pipeline, CRISPR-EZ consistently outperformed microinjection. Here, we provide an optimized protocol covering sgRNA synthesis, embryo collection, RNP electroporation, mouse generation, and genotyping strategies. Using CRISPR-EZ, a graduate-level researcher with basic embryo-manipulation skills can obtain genetically modified mice in 6 weeks. Altogether, CRISPR-EZ is a simple, economic, efficient, and high-throughput technology that is potentially applicable to other mammalian species.
Topics: Animals; CRISPR-Associated Protein 9; Clustered Regularly Interspaced Short Palindromic Repeats; Electroporation; Gene Editing; Mice; Mice, Inbred C57BL; Mice, Knockout; Microinjections; Zygote
PubMed: 29748649
DOI: 10.1038/nprot.2018.012 -
Therapeutic Delivery Jul 2018Delivering therapeutics in a painless manner is one of the many objectives for the treatment of clinical conditions. Micro and nanoneedles are small-scale devices that...
Delivering therapeutics in a painless manner is one of the many objectives for the treatment of clinical conditions. Micro and nanoneedles are small-scale devices that can help overcome the resistance encountered during drug diffusion by creating conduits of small dimensions through biomembranes. Microneedles for drug delivery applications were manually produced until the 1990s and after this the high precision technology from the semiconductor industry was adopted for their production [ 1 ]. Over the last decade or so, microneedles for transdermal applications have been widely studied. Currently, microneedle patches, mainly based on hyaluronates, are available over the counter for cosmetic applications. On the other hand, nanoneedles are used in atomic force microscopy, which has been explored for drug delivery and biosensing over the last two decades [ 2 , 3 ]. Micro and nanoneedle-based biosensing also poses potential for environment-responsive drug delivery. In this article, the current research, clinical studies and future perspectives of micro and nanoneedle-based systems are discussed for drug delivery and biosensing applications.
Topics: Administration, Cutaneous; Biosensing Techniques; Drug Delivery Systems; Humans; Microinjections; Nanostructures; Needles
PubMed: 29943686
DOI: 10.4155/tde-2018-0012 -
Zebrafish Dec 2017Microinjection is a widely used technique to inject defined volumes and concentrations of substances and explore their physiological function in vivo. The technique has...
Microinjection is a widely used technique to inject defined volumes and concentrations of substances and explore their physiological function in vivo. The technique has been particularly successful with zebrafish embryos; however, the injection equipment can be relatively expensive and therefore available only to well-funded laboratories. In this study, a simple, cheap, easy-to-assemble, and easy-to-use setup with a straightforward, accurate, and efficacious calibration method is introduced. The accuracy of this calibration method was tested by comparing with the results of calibration methods that are currently used in high-cost systems. Injection success with this low-cost system was verified based on the presence of injected dyes in zebrafish embryos, the absence of any significant morphological and behavioral differences between 3,4,-dichloroaniline-treated and untreated embryos, and larval viability.
Topics: Aniline Compounds; Animals; Coloring Agents; Embryo, Nonmammalian; Larva; Microinjections; Zebrafish
PubMed: 28678656
DOI: 10.1089/zeb.2017.1425 -
Advanced Healthcare Materials Dec 2015A novel trend is rapidly emerging in the use of microneedles, which are a miniaturized replica of hypodermic needles with length-scales of hundreds of micrometers, aimed... (Review)
Review
A novel trend is rapidly emerging in the use of microneedles, which are a miniaturized replica of hypodermic needles with length-scales of hundreds of micrometers, aimed at the transdermal biosensing of analytes of clinical interest, e.g., glucose, biomarkers, and others. Transdermal biosensing via microneedles offers remarkable opportunities for moving biosensing technologies and biochips from research laboratories to real-field applications, and envisages easy-to-use point-of-care microdevices with pain-free, minimally invasive, and minimal-training features that are very attractive for both developed and emerging countries. In addition to this, microneedles for transdermal biosensing offer a unique possibility for the development of biochips provided with end-effectors for their interaction with the biological system under investigation. Direct and efficient collection of the biological sample to be analyzed will then become feasible in situ at the same length-scale of the other biochip components by minimally trained personnel and in a minimally invasive fashion. This would eliminate the need for blood extraction using hypodermic needles and reduce, in turn, related problems, such as patient infections, sample contaminations, analysis artifacts, etc. The aim here is to provide a thorough and critical analysis of state-of-the-art developments in this novel research trend, and to bridge the gap between microneedles and biosensors.
Topics: Administration, Cutaneous; Animals; Biosensing Techniques; Drug Delivery Systems; Humans; Microinjections; Needles
PubMed: 26439100
DOI: 10.1002/adhm.201500450 -
Sensors (Basel, Switzerland) Mar 2024Microinjection is usually applied to the treatment of some retinal disorders, such as retinal vein cannulation and displaced submacular hemorrhage. Currently, the...
Microinjection is usually applied to the treatment of some retinal disorders, such as retinal vein cannulation and displaced submacular hemorrhage. Currently, the microinjection procedure is usually performed by using the viscous fluid control of a standard vitrectomy system, which applies a fixed air pressure through foot pedal activation. The injection process with the fixed pressure is uncontrollable and lacks feedback, the high flow rate of the injected drug may cause damage to the fundus tissue. In this paper, a liquid-driven microinjection system with a flow sensor is designed and developed specifically for fundus injection. In addition, a PID sliding mode control (SMC) method is proposed to achieve precise injection in the injection system. The experimental results of fundus simulation injection demonstrate that the microinjection system meets the requirements of fundus injection and reduces the impact of the injection process on the fundus tissue.
Topics: Animals; Microinjections; Abomasum; Computer Simulation; Fundus Oculi; Retinal Vein
PubMed: 38610350
DOI: 10.3390/s24072140 -
Current Protocols in Stem Cell Biology Nov 2014In this unit we introduce the derivation and genetic modification of mouse haploid embryonic stem (ES) cells. We detail how to produce haploid embryos and the subsequent... (Review)
Review
In this unit we introduce the derivation and genetic modification of mouse haploid embryonic stem (ES) cells. We detail how to produce haploid embryos and the subsequent ES derivation and cell culture. We further introduce readers to the intracytoplasmic injection processes of two types of haploid ES cells [androgenetic haploid ES (ahES) and parthenogenetic ES (phES)], both of which possess potential to produce fertile progenies by microinjection. This unit will be interesting to researchers who focus on recessive screens and transgenic animal model production with haploid stem cells.
Topics: Animals; Embryo, Mammalian; Mice; Microinjections; Mouse Embryonic Stem Cells; Parthenogenesis
PubMed: 25366896
DOI: 10.1002/9780470151808.sc01a06s31