Review

Authors: Jayoung Kim, Alan S Campbell, Berta Esteban-Fernández de Ávila...

Wearable biosensors are garnering substantial interest due to their potential to provide continuous, real-time physiological information via dynamic, noninvasive measurements of biochemical markers in biofluids, such as sweat, tears, saliva and interstitial fluid. Recent developments have focused on electrochemical and optical biosensors, together with advances in the noninvasive monitoring of biomarkers including metabolites, bacteria and hormones. A combination of multiplexed biosensing, microfluidic sampling and transport systems have been integrated, miniaturized and combined with flexible materials for improved wearability and ease of operation. Although wearable biosensors hold promise, a better understanding of the correlations between analyte concentrations in the blood and noninvasive biofluids is needed to improve reliability. An expanded set of on-body bioaffinity assays and more sensing strategies are needed to make more biomarkers accessible to monitoring. Large-cohort validation studies of wearable biosensor performance will be needed to underpin clinical acceptance. Accurate and reliable real-time sensing of physiological information using wearable biosensor technologies would have a broad impact on our daily lives.

Topics: Biosensing Techniques; Biotechnology; Body Fluids; Computer Systems; Humans; Iontophoresis; Lab-On-A-Chip Devices; Monitoring, Physiologic; Saliva; Sweat; Tears; Wearable Electronic Devices

PubMed: 30804534
DOI: 10.1038/s41587-019-0045-y

Meta-Analysis Review

Authors: L Bisset, A Paungmali, B Vicenzino...

A systematic review of the literature on the effectiveness of physical interventions for lateral epicondylalgia (tennis elbow) was carried out. Seventy six randomised controlled trials were identified, 28 of which satisfied the minimum criteria for meta-analysis. The evidence suggests that extracorporeal shock wave therapy is not beneficial in the treatment of tennis elbow. There is a lack of evidence for the long term benefit of physical interventions in general. However, further research with long term follow up into manipulation and exercise as treatments is indicated.

Topics: Acupuncture Therapy; Exercise Therapy; High-Energy Shock Waves; Humans; Iontophoresis; Laser Therapy; Massage; Musculoskeletal Manipulations; Pain; Physical Therapy Modalities; Randomized Controlled Trials as Topic; Tennis Elbow; Treatment Outcome

PubMed: 15976161
DOI: 10.1136/bjsm.2004.016170

Authors: Apipa Wanasathop, Patcharawan Nimmansophon, Michael Murawsky...

PURPOSE

Iontophoresis is a noninvasive method that enhances drug delivery using an electric field. This method can improve drug delivery to the tissues in the oral cavity. The effects of iontophoresis on gingival drug delivery have not been investigated. The objectives of this study were to (a) determine the flux enhancement of model permeants across porcine and human gingiva during iontophoresis, (b) examine the transport mechanisms of gingival iontophoresis, and (c) evaluate the potential of iontophoretically enhanced delivery for three model drugs lidocaine, ketorolac, and chlorhexidine.

METHODS

Passive and iontophoretic fluxes were determined with porcine and human gingiva using a modified Franz diffusion cell and model drugs and permeants. To investigate the transport mechanisms of iontophoresis, the enhancement from the direct-field effect was determined by positively and negatively charged model permeants. The electroosmosis enhancement effect was determined with neutral permeants of different molecular weight. The alteration of the gingival barrier due to electropermeabilization was evaluated using electrical resistance measurements.

RESULTS

Significant flux enhancement was observed during gingival iontophoresis. The direct-field effect was the major mechanism governing the iontophoretic transport of the charged permeants. Electroosmosis was from anode to cathode. The effective pore radius of the iontophoretic transport pathways in the porcine gingiva was ~0.68 nm. Irreversible electropermeabilization was observed after 2 and 4 h of iontophoresis under the conditions studied.

CONCLUSION

Iontophoresis could enhance drug delivery and reduce transport lag time, showing promise for gingival drug delivery.

Topics: Humans; Animals; Swine; Iontophoresis; Gingiva; Diffusion; Electroosmosis; Drug Delivery Systems; Administration, Cutaneous

PubMed: 37258949
DOI: 10.1007/s11095-023-03535-8

Authors: Deepal Vora, Harsha T Garimella, Carrie L German...

Psoriasis is a condition of the skin which involves scales, dry patches, and inflammation. Methotrexate (logP: -1.8, MW:454.44 g/mol) is administered orally or intravenously to treat psoriasis. The first-pass metabolism and systemic toxicity can be avoided by administration via skin. Topical and transdermal delivery of methotrexate using iontophoresis and microneedles, alone and in combination was investigated using full-thickness healthy human skin. It is also equally relevant to evaluate the delivery into and across damaged/diseased skin. Hence, this study investigated the delivery of methotrexate using ex vivo healthy and psoriatic human skin to understand the effect of skin disease condition on delivery of methotrexate via skin. A lower resistance and a higher TEWL for psoriatic skin indicated damaged barrier function, while histology studies indicated epithelial hyperproliferation and elongated rete ridges. Using the optimized iontophoretic parameters, there was no significant difference in receptor delivery for psoriatic skin (39.51 ± 4.45 µg/sq.cm) as compared to healthy skin (43.15 ± 0.83 µg/sq.cm). However, methotrexate delivery into psoriatic skin (126.23 ± 24.65 µg/sq.cm) was significantly higher as compared to healthy skin (12.02 ± 4.89 µg/sq.cm). Thus, significantly higher total delivery was observed from psoriatic skin than healthy skin.

Topics: Administration, Cutaneous; Humans; Iontophoresis; Methotrexate; Psoriasis; Skin

PubMed: 35331833
DOI: 10.1016/j.ijpharm.2022.121693

Review

Authors: Ripal Gaudana, Hari Krishna Ananthula, Ashwin Parenky...

Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. Static barriers (different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers), dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution), and efflux pumps in conjunction pose a significant challenge for delivery of a drug alone or in a dosage form, especially to the posterior segment. Identification of influx transporters on various ocular tissues and designing a transporter-targeted delivery of a parent drug has gathered momentum in recent years. Parallelly, colloidal dosage forms such as nanoparticles, nanomicelles, liposomes, and microemulsions have been widely explored to overcome various static and dynamic barriers. Novel drug delivery strategies such as bioadhesive gels and fibrin sealant-based approaches were developed to sustain drug levels at the target site. Designing noninvasive sustained drug delivery systems and exploring the feasibility of topical application to deliver drugs to the posterior segment may drastically improve drug delivery in the years to come. Current developments in the field of ophthalmic drug delivery promise a significant improvement in overcoming the challenges posed by various anterior and posterior segment diseases.

Topics: Administration, Topical; Colloids; Drug Delivery Systems; Eye; Half-Life; Humans; Iontophoresis; Melanins; Pharmacokinetics; Ultrasonics

PubMed: 20437123
DOI: 10.1208/s12248-010-9183-3

Authors: Siva Ram Kiran Vaka, H N Shivakumar, S Narasimha Murthy...

The objective of this study was to investigate the feasibility of rapid administration of iron via transdermal route as an alternative to parenteral route of administration. In vitro drug delivery studies were carried out using porcine epidermis mounted on Franz diffusion cells. The effect of chemical permeation enhancers and physical techniques (constant voltage iontophoresis, electroporation and combination of electroporation with iontophoresis) on the transport of ferric pyrophosphate (FPP) was studied. Transepidermal water loss (TEWL) and electrical resistance were measured in order to see the effect of these techniques on the skin barrier function. The amount of FPP permeated was not enhanced significantly with the use of any of the enhancers (P > 0.05). It was found that constant voltage iontophoresis (0.5, 2 or 4 V) for about 30 min across electroporated epidermis (120 V, 100 pulses, 10 ms at 5 Hz) enhanced the delivery of FPP over control in the range of 2- to 42-fold. Hence, a therapeutically required dose of iron could be delivered by transdermal route using electrically-mediated techniques.

Topics: Administration, Cutaneous; Anemia, Iron-Deficiency; Animals; Diphosphates; Drug Delivery Systems; Electroporation; Epidermis; Humans; Iontophoresis; Iron; Skin Absorption; Sus scrofa

PubMed: 20545483
DOI: 10.3109/10837450.2010.492219

Authors: Xin Rui Zhang, Yong Xun Jin, Pham Ngoc Chien...

BACKGROUND

Microneedles are tiny needles, typically ranging from tens to hundreds of micrometers in length, used in various medical procedures and treatments. The tested medical device named "CELLADEEP Patch" a dissolvable microneedle therapy system (MTS), made of hyaluronic acid and collagen. And the iontophoresis technique is also applied in the system. The study aimed to evaluate the effectiveness of the "CELLADEEP Patch" in skin improvement.

METHODS

Ex vivo human-derived skin tissue models were used in this study and they were divided into three different groups, namely, the Untreated Group, the Negative Control Group, and the Test Group respectively. The Untreated Group received no treatment measures, the Negative Control Group was exposed to ultraviolet B radiation (UVB) irradiation, and the Test Group was exposed to UVB irradiation and treated with "CELLADEEP Patch". Skin moisture content, transdermal water loss, and skin elasticity were evaluated by three clinical devices. Additionally, histological staining and related mRNA expression levels were also analyzed.

RESULTS

The results of skin moisture content, transdermal water loss, and skin elasticity evaluation consistently illustrated that the application of "CELLADEEP Patch" led to remarkable skin improvement. And the analysis of histological staining images also confirmed the effectiveness of the "CELLADEEP Patch", especially for increasing collagen density. Moreover, the upregulation of Collagen type 1 a (COL1A1) and hyaluronan synthase 3 mRNA expression and the decrease of Matrix metalloproteinase 1 (MMP-1) and Interleukin-1 beta (IL-1β) mRNA expression reflected its wrinkle improvement, moisturizing and anti-inflammation function.

CONCLUSION

"CELLADEPP Patch", the MTS combined with the iontophoresis technique, exhibits its effectiveness in moisturizing, skin elasticity improvement, and anti-inflammatory function when applied to ex vivo human-derived skin tissue models in experiments. The study has contributed to the understanding of the "CELLADEPP Patch" and laid the foundation for subsequent animal experiments and clinical trials.

Topics: Humans; Needles; Hyaluronic Acid; Iontophoresis; Skin; Collagen; Elasticity; Matrix Metalloproteinase 1; Interleukin-1beta; Ultraviolet Rays; Skin Aging; Water Loss, Insensible; Transdermal Patch; Collagen Type I

PubMed: 39031931
DOI: 10.1111/srt.13784

Review

Authors: Yuqi Zhang, Jicheng Yu, Anna R Kahkoska...

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

Review

Authors: Matthieu Roustit, Sophie Blaise, Jean-Luc Cracowski...

Iontophoresis is a method of non-invasive transdermal drug delivery based on the transfer of charged molecules using a low-intensity electric current. Both local and systemic administration are possible; however, the skin pharmacokinetics of iontophoretically delivered drugs is complex and difficult to anticipate. The unquestionable theoretical advantages of the technique make it attractive in several potential applications. After a brief review of the factors influencing iontophoresis, we detail the current applications of iontophoresis in therapeutics and the main potential applications under investigation, including systemic and topical drugs and focusing on the treatment of scleroderma-related ulcerations. Finally, we address the issue of safety, which could be a limitation to the routine clinical use of iontophoresis.

Topics: Administration, Cutaneous; Analgesics; Anesthetics, Local; Drug Delivery Systems; Humans; Iontophoresis; Models, Biological; Pharmaceutical Preparations; Scleroderma, Localized; Skin Absorption; Skin Ulcer; Vasoconstrictor Agents; Vasodilator Agents

PubMed: 23590287
DOI: 10.1111/bcp.12128

Meta-Analysis Review

Authors: Peter Kroeling, Anita Gross, Nadine Graham...

BACKGROUND

Neck pain is common, disabling and costly. The effectiveness of electrotherapy as a physiotherapeutic option remains unclear. This is an update of a Cochrane review first published in 2005 and previously updated in 2009.

OBJECTIVES

This systematic review assessed the short, intermediate and long-term effects of electrotherapy on pain, function, disability, patient satisfaction, global perceived effect, and quality of life in adults with neck pain with and without radiculopathy or cervicogenic headache.

SEARCH METHODS

We searched CENTRAL, MEDLINE, EMBASE, MANTIS, CINAHL, and ICL, without language restrictions, from their beginning to August 2012; handsearched relevant conference proceedings; and consulted content experts.

SELECTION CRITERIA

Randomized controlled trials (RCTs), in any language, investigating the effects of electrotherapy used primarily as unimodal treatment for neck pain. Quasi-RCTs and controlled clinical trials were excluded.

DATA COLLECTION AND ANALYSIS

We used standard methodological procedures expected by The Cochrane Collaboration. We were unable to statistically pool any of the results, but we assessed the quality of the evidence using an adapted GRADE approach.

MAIN RESULTS

Twenty small trials (1239 people with neck pain) containing 38 comparisons were included. Analysis was limited by trials of varied quality, heterogeneous treatment subtypes and conflicting results. The main findings for reduction of neck pain by treatment with electrotherapeutic modalities were as follows.Very low quality evidence determined that pulsed electromagnetic field therapy (PEMF) and repetitive magnetic stimulation (rMS) were more effective than placebo, while transcutaneous electrical nerve stimulation (TENS) showed inconsistent results.Very low quality evidence determined that PEMF, rMS and TENS were more effective than placebo.Low quality evidence (1 trial, 52 participants) determined that permanent magnets (necklace) were no more effective than placebo (standardized mean difference (SMD) 0.27, 95% CI -0.27 to 0.82, random-effects model).Very low quality evidence showed that modulated galvanic current, iontophoresis and electric muscle stimulation (EMS) were not more effective than placebo.There were four trials that reported on other outcomes such as function and global perceived effects, but none of the effects were of clinical importance. When TENS, iontophoresis and PEMF were compared to another treatment, very low quality evidence prevented us from suggesting any recommendations. No adverse side effects were reported in any of the included studies.

AUTHORS' CONCLUSIONS

We cannot make any definite statements on the efficacy and clinical usefulness of electrotherapy modalities for neck pain. Since the evidence is of low or very low quality, we are uncertain about the estimate of the effect. Further research is very likely to change both the estimate of effect and our confidence in the results. Current evidence for PEMF, rMS, and TENS shows that these modalities might be more effective than placebo. When compared to other interventions the quality of evidence was very low thus preventing further recommendations.Funding bias should be considered, especially in PEMF studies. Galvanic current, iontophoresis, EMS, and a static magnetic field did not reduce pain or disability. Future trials on these interventions should have larger patient samples, include more precise standardization, and detail treatment characteristics.

Topics: Electric Stimulation Therapy; Humans; Iontophoresis; Magnetic Field Therapy; Magnets; Musculoskeletal Pain; Neck Pain; Randomized Controlled Trials as Topic; Whiplash Injuries

PubMed: 23979926
DOI: 10.1002/14651858.CD004251.pub5