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Biomedicine & Pharmacotherapy =... Sep 2023Bone-related disorders treatment is a serious public health concern, imposing a significant social and economic burden on patients and healthcare systems. Although... (Review)
Review
Bone-related disorders treatment is a serious public health concern, imposing a significant social and economic burden on patients and healthcare systems. Although conventional drug delivery systems have made advances in bone diseases prevention and management, the limited delivery efficiency and convoluted focal environment lead to inadequate drug absorption and lack of specificity to achieve the intended therapeutic impact. Microneedle-based therapy represents an extraordinarily safe and well-tolerable therapeutic approach for treating bone disorders, providing improved efficacy by breaking down the barriers and delivery of therapeutic components to the target sites with programable release profiles in a less invasive manner. Over the past decades, numerous significant achievements in the development of various types of drug-carried microneedles have been made to address the obstacles encountered in the bone-treating procedure, enabling the microneedle-based therapy to take an important step in practical applications. In this light, this review summarizes these remarkable researches in terms of microneedles types and drug delivery strategies, with the goal of demonstrating the benefits of exploiting microneedle-based therapy as a novel strategy for treating bone-related disorders. The remaining challenges and future perspectives are also discussed in the hope of inspiring more efficient and intelligent bone treatment strategies.
Topics: Humans; Drug Delivery Systems; Pharmaceutical Preparations; Administration, Cutaneous; Bone Diseases; Needles; Microinjections
PubMed: 37531783
DOI: 10.1016/j.biopha.2023.115013 -
Journal of Visualized Experiments : JoVE Oct 2021The genus Strongyloides consists of multiple species of skin-penetrating nematodes with different host ranges, including Strongyloides stercoralis and Strongyloides...
The genus Strongyloides consists of multiple species of skin-penetrating nematodes with different host ranges, including Strongyloides stercoralis and Strongyloides ratti. S. stercoralis is a human-parasitic, skin-penetrating nematode that infects approximately 610 million people, while the rat parasite S. ratti is closely related to S. stercoralis and is often used as a laboratory model for S. stercoralis. Both S. stercoralis and S. ratti are easily amenable to the generation of transgenics and knockouts through the exogenous nucleic acid delivery technique of intragonadal microinjection, and as such, have emerged as model systems for other parasitic helminths that are not yet amenable to this technique. Parasitic Strongyloides adults inhabit the small intestine of their host and release progeny into the environment via the feces. Once in the environment, the larvae develop into free-living adults, which live in feces and produce progeny that must find and invade a new host. This environmental generation is unique to the Strongyloides species and similar enough in morphology to the model free-living nematode Caenorhabditis elegans that techniques developed for C. elegans can be adapted for use with these parasitic nematodes, including intragonadal microinjection. Using intragonadal microinjection, a wide variety of transgenes can be introduced into Strongyloides. CRISPR/Cas9 components can also be microinjected to create mutant Strongyloides larvae. Here, the technique of intragonadal microinjection into Strongyloides, including the preparation of free-living adults, the injection procedure, and the selection of transgenic progeny, is described. Images of transgenic Strongyloides larvae created using CRISPR/Cas9 mutagenesis are included. The aim of this paper is to enable other researchers to use microinjection to create transgenic and mutant Strongyloides.
Topics: Animals; Animals, Genetically Modified; Caenorhabditis elegans; Humans; Microinjections; Rats; Strongyloides ratti; Strongyloides stercoralis
PubMed: 34694289
DOI: 10.3791/63023 -
Advanced Drug Delivery Reviews Oct 2023In the field of ocular drug delivery, topical delivery remains the most common treatment option for managing anterior segment diseases, whileintraocular injectionsare... (Review)
Review
In the field of ocular drug delivery, topical delivery remains the most common treatment option for managing anterior segment diseases, whileintraocular injectionsare the current gold standard treatment option for treating posterior segment diseases. Nonetheless, topical eye drops are associated with low bioavailability (<5%), and theintravitreal administration procedure is highly invasive, yielding poor patient acceptability. In both cases, frequent administration is currently required. As a result, there is a clear unmet need for sustained drug delivery to the eye, particularly in a manner that can be localised. Microneedles, which are patches containing an array of micron-scale needles (<1 mm), have the potential to meet this need. These platforms can enable localised drug delivery to the eye while enhancing penetration of drug molecules through key ocular barriers, thereby improving overall therapeutic outcomes. Moreover, the minimally invasive manner in which microneedles are applied could provide significant advantages over traditional intravitreal injections regarding patient acceptability. Considering the benefitsofthis novel ocular delivery system, this review provides an in-depth overviewofthe microneedle systems for ocular drug delivery, including the types of microneedles used and therapeutics delivered. Notably, we outline and discuss the current challenges associated with the clinical translation of these platforms and offer opinions on factors which should be considered to improve such transition from lab to clinic.
Topics: Humans; Drug Delivery Systems; Eye; Pharmaceutical Preparations; Needles; Microinjections; Administration, Cutaneous
PubMed: 37678648
DOI: 10.1016/j.addr.2023.115082 -
Developmental Biology Oct 2023Genome manipulation methods in C. elegans require microinjecting DNA or ribonucleoprotein complexes into the microscopic core of the gonadal syncytium. These...
Genome manipulation methods in C. elegans require microinjecting DNA or ribonucleoprotein complexes into the microscopic core of the gonadal syncytium. These microinjections are technically demanding and represent a key bottleneck for all genome engineering and transgenic approaches in C. elegans. While there have been steady improvements in the ease and efficiency of genetic methods for C. elegans genome manipulation, there have not been comparable advances in the physical process of microinjection. Here, we report a simple and inexpensive method for handling worms using a paintbrush during the injection process that nearly tripled average microinjection rates compared to traditional worm handling methods. We found that the paintbrush increased injection throughput by substantially increasing both injection speeds and post-injection survival rates. In addition to dramatically and universally increasing injection efficiency for experienced personnel, the paintbrush method also significantly improved the abilities of novice investigators to perform key steps in the microinjection process. We expect that this method will benefit the C. elegans community by increasing the speed at which new strains can be generated and will also make microinjection-based approaches less challenging and more accessible to personnel and labs without extensive experience.
Topics: Animals; Caenorhabditis elegans; Microinjections; Animals, Genetically Modified; Germ Cells; DNA; CRISPR-Cas Systems
PubMed: 37433390
DOI: 10.1016/j.ydbio.2023.07.003 -
Skin Research and Technology : Official... Apr 2023Compared with systemic administration methods like injection and oral administration, traditional transdermal drug delivery has the advantages of rapid onset of activity... (Review)
Review
BACKGROUND
Compared with systemic administration methods like injection and oral administration, traditional transdermal drug delivery has the advantages of rapid onset of activity and low side effects. However, hydrophilic drugs and bioactive substances are often unsuitable for traditional transdermal drug delivery.
METHODS
The application of microneedles made from gelatin methylacryloyl (GelMA) has greatly expanded thepossibilities for skin transdermal drug delivery. We have reviewed the latest literatures about the dermatological application of GelMA hydrogel microneedles in recent years using Google Scholar, PubMed and Springer.
RESULTS
GelMA hydrogel microneedles exhibit huge potency in the diagnosis and treatment of skin diseases, and this technology also brings broad application prospects for subcutaneous micro-invasive transdermal targeted drug delivery, which mainly used in skin tissue fluid collection, local substance delivery and wound healing.
CONCLUSION
With in-depth research on GelMA hydrogel, this technology will bring more breakthroughs and developments in the clinical diagnosis and treatment of skin diseases.
Topics: Humans; Gelatin; Hydrogels; Drug Delivery Systems; Microinjections; Skin; Administration, Cutaneous; Needles
PubMed: 37113084
DOI: 10.1111/srt.13327 -
Journal of Visualized Experiments : JoVE Mar 2023The cerebral cortex is the outermost brain structure and is responsible for the processing of sensory input and motor output; it is seen as the seat of higher-order...
The cerebral cortex is the outermost brain structure and is responsible for the processing of sensory input and motor output; it is seen as the seat of higher-order cognitive abilities in mammals, in particular, primates. Studying gene functions in primate brains is challenging due to technical and ethical reasons, but the establishment of the brain organoid technology has enabled the study of brain development in traditional primate models (e.g., rhesus macaque and common marmoset), as well as in previously experimentally inaccessible primate species (e.g., great apes), in an ethically justifiable and less technically demanding system. Moreover, human brain organoids allow the advanced investigation of neurodevelopmental and neurological disorders. As brain organoids recapitulate many processes of brain development, they also represent a powerful tool to identify differences in, and to functionally compare, the genetic determinants underlying the brain development of various species in an evolutionary context. A great advantage of using organoids is the possibility to introduce genetic modifications, which permits the testing of gene functions. However, the introduction of such modifications is laborious and expensive. This paper describes a fast and cost-efficient approach to genetically modify cell populations within the ventricle-like structures of primate cerebral organoids, a subtype of brain organoids. This method combines a modified protocol for the reliable generation of cerebral organoids from human-, chimpanzee-, rhesus macaque-, and common marmoset-derived induced pluripotent stem cells (iPSCs) with a microinjection and electroporation approach. This provides an effective tool for the study of neurodevelopmental and evolutionary processes that can also be applied for disease modeling.
Topics: Animals; Humans; Macaca mulatta; Callithrix; Microinjections; Brain; Induced Pluripotent Stem Cells; Electroporation; Organoids; Mammals
PubMed: 37036224
DOI: 10.3791/65176 -
Journal of Controlled Release :... Jul 2024Microneedles (MNs) are micron-sized needles, typically <2 mm in length, arranged either as an array or as single needle. These MNs offer a minimally invasive approach... (Review)
Review
Microneedles (MNs) are micron-sized needles, typically <2 mm in length, arranged either as an array or as single needle. These MNs offer a minimally invasive approach to ocular drug delivery due to their micron size (reducing tissue damage compared to that of hypodermic needles) and overcoming significant barriers in drug administration. While various types of MNs have been extensively researched, significant progress has been made in the use of hollow MNs (HMNs) for ocular drug delivery, specifically through suprachoroidal injections. The suprachoroidal space, situated between the sclera and choroid, has been targeted using optical coherence tomography-guided injections of HMNs for the treatment of uveitis. Unlike other MNs, HMNs can deliver larger volumes of formulations to the eye. This review primarily focuses on the use of HMNs in ocular drug delivery and explores their ocular anatomy and the distribution of formulations following potential HMN administration routes. Additionally, this review focuses on the influence of formulation characteristics (e.g., solution viscosity, particle size), HMN properties (e.g., bore or lumen diameter, MN length), and routes of administration (e.g., periocular transscleral, suprachoroidal, intravitreal) on the ocular distribution of drugs. Overall, this paper highlights the distinctive properties of HMNs, which make them a promising technology for improving drug delivery efficiency, precision, and patient outcomes in the treatment of ocular diseases.
Topics: Needles; Humans; Drug Delivery Systems; Animals; Administration, Ophthalmic; Eye; Pharmaceutical Preparations; Microinjections
PubMed: 38735395
DOI: 10.1016/j.jconrel.2024.05.013 -
Annual International Conference of the... Nov 2021Microinjection is a widely used technique employed by biologists with applications in transgenesis, cryopreservation, mutagenesis, labeling/dye injection and in-vitro...
Microinjection is a widely used technique employed by biologists with applications in transgenesis, cryopreservation, mutagenesis, labeling/dye injection and in-vitro fertilization. However, microinjection is an extremely laborious manual procedure, which makes it a critical bottleneck in the field and thus ripe for automation. Here, we present a computer-guided robot that automates the targeted microinjection of Drosophila melanogaster and zebrafish (Danio rerio) embryos, two important model organisms in biological research. The robot uses a series of cameras to image an agar plate containing embryos at multiple magnifications and perspectives. This imaging is combined with machine learning and computer vision algorithms to pinpoint a location on the embryo for targeted microinjection with microscale precision. We demonstrate the utility of this microinjection robot to successfully microinject Drosophila melanogaster and zebrafish embryos. Results obtained indicate that the robotic microinjection approach can significantly increase the throughput of microinjection as compared to manual microinjection while maintaining survival rates comparable to human operators. In the future, this robotic platform can be used to perform high throughput microinjection experiments and can be extended to automatically microinject a host of organisms such as roundworms (Caenorhabditis elegans), mosquito (Culicidae) embryos, sea urchins (Echinoidea) and frog (Xenopus) oocytes.
Topics: Animals; Drosophila melanogaster; Microinjections; Robotic Surgical Procedures; Robotics; Zebrafish
PubMed: 34892294
DOI: 10.1109/EMBC46164.2021.9630858 -
Journal of Controlled Release :... Oct 2016Millions of people die of infectious diseases each year, mostly in developing countries, which could largely be prevented by the use of vaccines. While immunization... (Review)
Review
Millions of people die of infectious diseases each year, mostly in developing countries, which could largely be prevented by the use of vaccines. While immunization rates have risen since the introduction of the Expanded Program on Immunization (EPI), there remain major challenges to more effective vaccination in developing countries. As a possible solution, microneedle patches containing an array of micron-sized needles on an adhesive backing have been developed to be used for vaccine delivery to the skin. These microneedle patches can be easily and painlessly applied by pressing against the skin and, in some designs, do not leave behind sharps waste. The patches are single-dose, do not require reconstitution, are easy to administer, have reduced size to simplify storage, transportation and waste disposal, and offer the possibility of improved vaccine immunogenicity, dose sparing and thermostability. This review summarizes vaccination challenges in developing countries and discusses advantages that microneedle patches offer for vaccination to address these challenges. We conclude that microneedle patches offer a powerful new technology that can enable more effective vaccination in developing countries.
Topics: Animals; Communicable Disease Control; Communicable Diseases; Developing Countries; Humans; Injections, Intradermal; Microinjections; Needles; Transdermal Patch; Vaccination
PubMed: 26603347
DOI: 10.1016/j.jconrel.2015.11.019 -
Systems Biology in Reproductive Medicine Jun 2010Echinoderms are closely related to chordates and comprise a major group of invertebrate deuterostomes. They are broadcast spawners and as such, each female accumulates... (Review)
Review
Echinoderms are closely related to chordates and comprise a major group of invertebrate deuterostomes. They are broadcast spawners and as such, each female accumulates millions of eggs and oocytes. These cells are readily isolated, and are often large, clear, and surrounded by accessory cells and extracellular coverings that do not prevent access to the oocyte. Sea star oocytes are stored in prophase of meiosis, and since the natural meiotic stimulus has been identified as 1-methyladenine, these cells can be induced to complete meiotic maturation as individuals, or synchronously en masse. Microinjection and culture of these cells is feasible using quantitative or repetitive methods so that hundreds of oocytes and eggs can be modified each hour. Experimentation on this organism is extensive over a rich history of reproductive and developmental biology so that new investigators can easily incorporate this organism into their repertoire of research. This review will highlight the fundamental protocols to enable a new investigator to perform an array of approaches on this organism, including oocyte isolation, microinjection, and even single cell quantitative PCR.
Topics: Animals; Cell Separation; Environmental Exposure; Female; Male; Microinjections; Models, Animal; Oocytes; Reproduction; Spermatozoa; Starfish
PubMed: 20536323
DOI: 10.3109/19396361003674879