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Pharmaceutics Feb 2023Microneedles (MNs) have been widely used in biomedical applications for drug delivery and biomarker detection purposes. Furthermore, MNs can also be used as a... (Review)
Review
Microneedles (MNs) have been widely used in biomedical applications for drug delivery and biomarker detection purposes. Furthermore, MNs can also be used as a stand-alone tool to be combined with microfluidic devices. For that purpose, lab- or organ-on-a-chip are being developed. This systematic review aims to summarize the most recent progress in these emerging systems, to identify their advantages and limitations, and discuss promising potential applications of MNs in microfluidics. Therefore, three databases were used to search papers of interest, and their selection was made following the guidelines for systematic reviews proposed by PRISMA. In the selected studies, the MNs type, fabrication strategy, materials, and function/application were evaluated. The literature reviewed showed that although the use of MNs for lab-on-a-chip has been more explored than for organ-on-a-chip, some recent studies have explored this applicability with great potential for the monitoring of organ models. Overall, it is shown that the presence of MNs in advanced microfluidic devices can simplify drug delivery and microinjection, as well as fluid extraction for biomarker detection by using integrated biosensors, which is a promising tool to precisely monitor, in real-time, different kinds of biomarkers in lab- and organ-on-a-chip platforms.
PubMed: 36986653
DOI: 10.3390/pharmaceutics15030792 -
The Journal of Dermatology Apr 2023Intra- and transdermal administration of substances via percutaneous injection is effective but considered painful, and inconvenient in addition to bringing forth... (Review)
Review
Intra- and transdermal administration of substances via percutaneous injection is effective but considered painful, and inconvenient in addition to bringing forth biohazardous waste material. In contrast to injection, topical drug application, which includes ointments, creams and lotions, increases the local drug load. Moreover, it has reduced side effects compared to systemic administration. However, the epidermis poses a barrier to high molecular weight substances, limiting the delivery efficiency. Dissolving microneedles (DMN) are hydrophilic, mostly polymer-based constructs that are capable of skin penetration and were developed to provide painless and direct dermal drug delivery. This systematic review provides a comprehensive overview of the available clinical evidence for the use of DMN to treat various skin conditions. According to the PRISMA statement, a systematic search for articles on the use of DMN for dermatological indications was conducted on three different databases (Pubmed, Embase, and the Cochrane library). Only human clinical trials were considered. Qualitative assessment was done by two separate reviewers using the Cochrane risk of bias (RoB 2) and Chambers' criteria assessment tools. The search yielded 1090 articles. After deduplication and removal of ineligible records, 889 records were screened on title and abstract. Full text screening was done for 18 articles and ultimately 17 articles were included of which 15 were randomized controlled trials and two were case series. The quality assessment showed that the majority of included studies had low to no risk of bias. Clinical data supports that DMN are an excellent, effective, and pain free drug delivery method for multiple dermatological disorders including skin aging, hyperpigmentation, psoriasis, warts, and keloids by supplying a painless and effective vehicle for intradermal/intralesional drug administration. Microneedle technology provides a promising non- to minimally-invasive alternative to percutaneous injection.
Topics: Humans; Microinjections; Skin; Administration, Cutaneous; Drug Delivery Systems; Epidermis; Needles; Pain
PubMed: 36700529
DOI: 10.1111/1346-8138.16732 -
Dermatologic Surgery : Official... Dec 2020Melasma is an acquired disorder of hyperpigmentation that is often recalcitrant to current therapies. Microneedling is used to treat scars, striae, and rhytides and has... (Comparative Study)
Comparative Study
BACKGROUND
Melasma is an acquired disorder of hyperpigmentation that is often recalcitrant to current therapies. Microneedling is used to treat scars, striae, and rhytides and has a relatively low risk of post-treatment dyspigmentation. Several studies have examined its use in melasma.
OBJECTIVE
To review the published evidence on the efficacy and safety of microneedling in the treatment of melasma.
METHODS
A systematic review was performed. A meta-analysis could not be performed because of methodological differences across studies and data heterogeneity.
RESULTS
Eight studies were included for analysis. Most studies assessed the utility of microneedling in combination with other topical therapies and detected some success. However, microneedling-mediated transdermal delivery of medications is not superior to microinjections of medications. There is less evidence supporting the use of microneedling as monotherapy. Microneedling, when used with a 1064-nm Q-switched Nd:YAG laser, may provide additional benefit, although with a risk of post-treatment dyspigmentation.
CONCLUSION
Based on low-quality evidence, microneedling may play a role in the treatment of melasma, with the mechanism of action likely being the facilitation of delivery of topical therapies to the epidermis and dermis, and one ancillary benefit of this approach being the very low risk of postinflammatory hyperpigmentation.
Topics: Administration, Cutaneous; Combined Modality Therapy; Dermatologic Agents; Dry Needling; Humans; Melanosis; Microinjections; Needles; Transdermal Patch; Treatment Outcome
PubMed: 32897944
DOI: 10.1097/DSS.0000000000002763 -
Advanced Drug Delivery Reviews 2020Microneedles (MNs) have been used to deliver drugs for over two decades. These platforms have been proven to increase transdermal drug delivery efficiency dramatically...
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.
Topics: Administration, Topical; Biological Transport; Drug Delivery Systems; Equipment Design; Humans; Microinjections; Microtechnology; Polymers; Prostheses and Implants
PubMed: 31837356
DOI: 10.1016/j.addr.2019.11.010 -
Animal Genetics Jun 2024Transgenic (Tg) animal technology is one of the growing areas in biology. Various Tg technologies, each with its own advantages and disadvantages, are available for... (Comparative Study)
Comparative Study
Transgenic (Tg) animal technology is one of the growing areas in biology. Various Tg technologies, each with its own advantages and disadvantages, are available for generating Tg animals. These include zygote microinjection, electroporation, viral infection, embryonic stem cell or spermatogonial stem cell-mediated production of Tg animals, sperm-mediated gene transfer (SMGT), and testis-mediated gene transfer (TMGT). However, there are currently no comprehensive studies comparing SMGT and TMGT methods, selecting appropriate gene delivery carriers (such as nanoparticles and liposomes), and determining the optimal route for gene delivery (SMGT and TMGT) for producing Tg animal. Here we aim to provide a comprehensive assessment comparing SMGT and TMGT methods, and to introduce the best carriers and gene transfer methods to sperm and testis to generate Tg animals in different species. From 2010 to 2022, 47 studies on SMGT and 25 studies on TMGT have been conducted. Mice and rats were the most commonly used species in SMGT and TMGT. Regarding the SMGT approach, nanoparticles, streptolysin-O, and virus packaging were found to be the best gene transfer methods for generating Tg mice. In the TMGT method, the best gene transfer methods for generating Tg mice and rats were virus packaging, dimethyl sulfoxide, electroporation, and liposome. Our study has shown that the efficiency of producing Tg animals varies depending on the species, gene carrier, and method of gene transfer.
Topics: Animals; Male; Mice; Rats; Animals, Genetically Modified; Gene Transfer Techniques; Spermatozoa; Testis
PubMed: 38361185
DOI: 10.1111/age.13404 -
Human Reproduction Update 2016ICSI is currently the most commonly used assisted reproductive technology, accounting for 70-80% of the cycles performed. This extensive use, even excessive, is partly... (Review)
Review
BACKGROUND
ICSI is currently the most commonly used assisted reproductive technology, accounting for 70-80% of the cycles performed. This extensive use, even excessive, is partly due to the high level of standardization reached by the procedure. There are, however, some aspects that deserve attention and can still be ameliorated. The aim of this systematic review was to evaluate the results of available publications dealing with the management of specific situations during ICSI in order to support embryologists in trying to offer the best laboratory individualized treatment.
METHODS
This systematic review is based on material obtained by searching PUBMED between January 1996 and March 2015. We included peer-reviewed, English-language journal articles that have evaluated ICSI outcomes in the case of (i) immature oocytes, (ii) oocyte degeneration, (iii) timing of the various phases, (iv) polar body position during injection, (v) zona-free oocytes, (vi) fertilization deficiency, (vii) round-headed sperm, (viii) immotile sperm and (ix) semen samples with high DNA fragmentation.
RESULTS
More than 1770 articles were obtained, from which only 90 were specifically related to the issues developed for female gametes and 55 for the issues developed for male gametes. The studies selected for this review were organized in order to provide a guide to overcome roadblocks. According to these studies, the injection of rescue metaphase I oocytes should be discouraged due to poor clinical outcomes and a high aneuploidy rates; laser-assisted ICSI represents an efficient method to solve the high oocyte degeneration rate; the optimal ICSI timing and the best polar body position during the injection have not been clarified; injected zona-free oocytes, if handled carefully, can develop up to blastocyst stage and implant; efficient options can be offered to patients who suffered fertilization failure in previous conventional ICSI cycles. Most controversial and inconclusive are data on the best method to select a viable spermatozoa when only immotile spermatozoa are available for ICSI and, to date, there is no reliable approach to completely filter out spermatozoa with fragmented DNA from an ejaculate. However, most of the studies do not report essential clinical outcomes, such as live birth, miscarriage and fetal abnormality rate, which are essential to establish the safety of a procedure.
CONCLUSIONS
This review provides the current knowledge on some controversial technical aspects of the ICSI procedures in order to improve its efficacy in specific contexts. Notwithstanding that embryologists might benefit from the approaches presented herein in order to improve ICSI outcomes, this area of expertise still demands a greater number of well-designed studies, especially in order to solve open issues about the safety of these procedures.
Topics: Asthenozoospermia; DNA Fragmentation; Female; Fertilization; Humans; Male; Metaphase; Microinjections; Oocytes; Pregnancy; Sperm Injections, Intracytoplasmic; Spermatozoa
PubMed: 26586241
DOI: 10.1093/humupd/dmv050 -
The Cochrane Database of Systematic... 2003In vitro fertilisation (IVF) as treatment for male factor subfertility is associated with lower fertilisation and pregnancy rates than for other indications. Since the... (Review)
Review
BACKGROUND
In vitro fertilisation (IVF) as treatment for male factor subfertility is associated with lower fertilisation and pregnancy rates than for other indications. Since the late 1980s several assisted fertilisation techniques have emerged and have been rapidly developed to try to enhance results for couples with male factor subfertility, or to help couples with severe male factor for whom conventional IVF was not possible. The techniques of partial zona dissection (PZD) and of subzonal microinjection of spermatozoa into the perivitelline space (SUZI) are by far surpassed by the technique of intra-cytoplasmatic sperm injection (ICSI). ICSI has proven to be the therapy of choice for couples with severe male factor subfertility.
OBJECTIVES
To investigate whether ICSI improves livebirth rate in comparison to IVF in couples with non-male subfertility.
SEARCH STRATEGY
We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (searched 30 May 2002), the Cochrane Controlled Trials Register (Cochrane Library Issue 2, 2002), PubMed (January 1992 to July 2002) and reference lists of articles.
SELECTION CRITERIA
Trials were included if they compared the effects of these techniques on livebirths, pregnancy and fertilisation outcomes. Only randomised studies were included in this review.
DATA COLLECTION AND ANALYSIS
One study met the inclusion criteria for this review. The study compared ICSI with IVF within couples with non-male infertility. Data was extracted independently by two reviewers.
MAIN RESULTS
There were no randomised data comparing livebirth rates. The single identified study did not find a difference in pregnancy rates (OR 1.4, 95% CI 0.95 to 2.2). There were no randomised data on miscarriage rates, or on other adverse events such as congenital malformations that may be of concern.
REVIEWER'S CONCLUSIONS
Whether ICSI should be preferred to IVF for cases of non-male factor subfertility remains an open question. Further research should report livebirth rates and adverse events.
Topics: Embryo Implantation; Female; Fertilization in Vitro; Humans; Infertility; Randomized Controlled Trials as Topic; Sperm Injections, Intracytoplasmic
PubMed: 12804403
DOI: 10.1002/14651858.CD001301 -
Cureus May 2024Patterned hair loss (PHL) is a severe hair condition that affects both sexes. Mesotherapy is a treatment that involves microinjecting medications and/or vitamins into... (Review)
Review
Patterned hair loss (PHL) is a severe hair condition that affects both sexes. Mesotherapy is a treatment that involves microinjecting medications and/or vitamins into the middle layer of the skin. Mesotherapy reduces systemic adverse effects by delivering drugs directly to the hair follicle, increasing local bioavailability while lowering systemic exposure. Local side effects and reactions may develop due to mesotherapy. This study systematically evaluated the safety and efficacy of mesotherapy to minoxidil 5%, as well as addressing its limitations, dosing, and technique, with the intent of providing valuable trials and insights for clinicians and patients considering mesotherapy for improved androgenetic alopecia (AGA) outcomes. The literature search carried out by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria yielded 11 relevant studies from an initial pool of 18 articles. These studies covered various aspects of the role of mesotherapy and minoxidil in AGA, including techniques, complications, limitations, and outcomes. In conclusion, available trials and research on mesotherapy and minoxidil demonstrated excellent statistical significance and a high patient satisfaction rate, with the exception of two publications that took into account certain uncommon adverse effects of mesotherapy. However, recent research suggests that a mesotherapy method for alopecia with a low risk of side effects is effective.
PubMed: 38841017
DOI: 10.7759/cureus.59705 -
Drug Development and Industrial Pharmacy Feb 2019Transdermal route has been explored for various agents due to its advantage of bypassing the first pass effect and sustained release of drug. Due to strong barrier...
Transdermal route has been explored for various agents due to its advantage of bypassing the first pass effect and sustained release of drug. Due to strong barrier properties of the skin, mainly stratum corneum (SC), the delivery of many therapeutic agents across the skin has become challenging. Few drugs with specific physicochemical properties (molecular weight <500 Da, adequate lipophilicity, and low melting point) can be effectively administered via transdermal route. However, delivery of hydrophilic drugs and macromolecular agents including peptides, DNA and small interfering RNA is challenging. Drug penetration through the SC may involve bypass or reversible disruption of SC layer by various means. Recently, the use of micron-scale needles has been proposed in increasing skin permeability and shown to dramatically increase permeation, especially for macromolecules. Microneedles (MNs) can penetrate through the SC layer of the skin into the viable epidermis, avoiding contact with nerve fibers and blood vessels that reside primarily in the dermal layer. This review summarizes the types of MNs and fabrication techniques of different types of MNs. The safety aspects of the materials used for fabrication have been discussed in detail. Biological applications and relevant phase III clinical trials are also highlighted.
Topics: Administration, Cutaneous; Animals; Drug Delivery Systems; Humans; Microinjections; Needles
PubMed: 30348022
DOI: 10.1080/03639045.2018.1539497 -
The Cochrane Database of Systematic... 2000In vitro fertilisation (IVF) and embryo transfer as treatment for male factor infertility is associated with lower fertilisation and pregnancy rates than for other... (Review)
Review
BACKGROUND
In vitro fertilisation (IVF) and embryo transfer as treatment for male factor infertility is associated with lower fertilisation and pregnancy rates than for other indications. Since the late 1980s several assisted fertilisation techniques have emerged and have been rapidly developed to try to enhance results for couples with male factor infertility, or to help couples with severe male factor for whom conventional IVF was not possible. The technique of partial zona dissection (PZD) was developed to increase the probability that a sperm capable of fertilisation comes in contact with the oocyte. Although this method improved conventional IVF results, the improvement was only marginal and relatively large numbers of sperm are still required. This drawback applied less to the subsequent technique of subzonal microinjection of spermatozoa into the perivitelline space (SUZI). However, for all of these techniques fertilisation rates remained low, rates of polyspermic fertilisation were increased, and cases with a very limited number of spermatozoa in the ejaculate could still not be treated. The advent of intra-cytoplasmatic sperm injection (ICSI) of a single sperm (or sperm head or nucleus) into the oocyte appears to be an important breakthrough.
OBJECTIVES
To investigate whether ICSI improves fertilisation and/or pregnancy rates in comparison to other fertilisation techniques.
SEARCH STRATEGY
The Menstrual Disorders and Subfertility Group search strategy (see Review Group details) was used to identify trials that had compared ICSI with other infertility techniques, such as PZD, SUZI, conventional IVF and additional IVF.
SELECTION CRITERIA
Trials were included if they compared the effects of these techniques on fertilisation and pregnancy outcomes. Only randomised studies were included in this review.
DATA COLLECTION AND ANALYSIS
Ten studies met the inclusion criteria for this review. Eight studies compared ICSI with conventional IVF. One study compared ICSI with SUZI and one study compared ICSI with additional IVF. Data was extracted independently by two reviewers. Where relevant data was missing or unclear, the authors had been consulted. Male participants were classified according to their semen parameters, i.e. normal semen (concentration >20 million per ml, motility >50%, morphology >14%), borderline semen (concentration 10-20 million per ml, motility 30-50%, morphology 4-14% normal forms) and very poor semen (concentration <10 million per ml, motility <30%, morphology <4% normal forms).
MAIN RESULTS
For couples with normal semen there is no evidence of a difference in fertilisation rates per retrieved oocyte or pregnancy rates between ICSI and conventional IVF. On the other hand, for fertilisation rate per inseminated oocyte, ICSI appears to result in better outcomes than IVF for normal semen. For couples with borderline semen ICSI results in higher fertilisation rates (all) than IVF. Couples with very poor semen will have better fertilisation outcomes with ICSI than with SUZI or additional IVF.
REVIEWER'S CONCLUSIONS
There is evidence from this systematic review that fertilisation rates are significantly better with ICSI than IVF in couples with borderline semen. When the semen parameters are normal there is insufficient evidence of a difference in effectiveness between ICSI and IVF when retrieved oocytes were the unit of randomisation. However, there was a small but statistically significant increase in fertilisation rate when inseminated oocytes were the unit of randomisation. Total fertilisation rates were significantly reduced in ICSI cycles than IVF but there were no damaged oocytes in IVF cycles regardless of the semen parameters.
Topics: Embryo Implantation; Female; Fertilization in Vitro; Humans; Sperm Injections, Intracytoplasmic
PubMed: 10796764
DOI: 10.1002/14651858.CD001301