Reverse Iontophoretic Extraction of Skin Cancer-Related Biomarkers

Non-invasive methods for early diagnosis of skin cancer are highly valued. One possible approach is to monitor relevant biomarkers such as tryptophan (Trp) and kynurenine (Kyn), on the skin surface. The primary aim of this in vitro investigation was, therefore, to examine whether reverse iontophoresis (RI) can enhance the extraction of Trp and Kyn, and to demonstrate how the Trp/Kyn ratio acquired from the skin surface reflects that in the epidermal tissue. The study also explored whether the pH of the receiver medium impacted on extraction efficiency, and assessed the suitability of a bicontinuous cubic liquid crystal as an alternative to a simple buffer solution for this purpose. RI substantially enhanced the extraction of Trp and Kyn, in particular towards the cathode. The Trp/Kyn ratio obtained on the surface matched that in the viable skin. Increasing the receiver solution pH from 4 to 9 improved extraction of both analytes, but did not significantly change the Trp/Kyn ratio. RI extraction of Trp and Kyn into the cubic liquid crystal was comparable to that achieved with simple aqueous receiver solutions. We conclude that RI offers a potential for non-invasive sampling of low-molecular weight biomarkers and further investigations in vivo are therefore warranted.

IONTOPHORESIS: A FUNCTIONAL APPROACH FOR ENHANCEMENT OF TRANSDERMAL DRUG DELIVERY

Iontophoresis is one of the most widely studied active techniques for enhancing transdermal delivery of drugs. However, its ability to enhance the delivery of highly lipophilic compounds is poor due to lack of any charge and poor water solubility of molecules. The skin has been used as a port for systemic delivery of therapeutic agents since several decades. The composition of stratum corneum renders it a daunting barrier to the topical and transdermal administration of therapeutic agents. The number of drug molecules for transdermal delivery is limited owing to the physicochemical restrictions. The delivery of drugs into systemic circulation via skin has generated much attention during the last decade. Transdermal therapeutic systems propound controlled release of active ingredients through the skin and into the systemic circulation in a predictive manner. Drugs administered through these systems escape first-pass metabolism and maintain a steady state scenario similar to a continuous intravenous infusion for up to several days. Keywords: Iontophoresis, non-invasive, stratum corneum, acid-alkaline reaction, chemical permeation enhancer, reverse iontophoresis.

Sampling of fluid through skin with magnetohydrodynamics for noninvasive glucose monitoring

Out of 463 million people currently with diabetes, 232 million remain undiagnosed. Diabetes is a threat to human health, which could be mitigated via continuous self-monitoring of glucose. In addition to blood, interstitial fluid is considered to be a representative sample for glucose monitoring, which makes it highly attractive for wearable on-body sensing. However, new technologies are needed for efficient and noninvasive sampling of interstitial fluid through the skin. In this report, we introduce the use of Lorentz force and magnetohydrodynamics to noninvasively extract dermal interstitial fluid. Using porcine skin as an ex-vivo model, we demonstrate that the extraction rate of magnetohydrodynamics is superior to that of reverse iontophoresis. This work seeks to provide a safe, effective, and noninvasive sampling method to unlock the potential of wearable sensors in needle-free continuous glucose monitoring devices that can benefit people living with diabetes.

Novel glucose-responsive of the transparent nanofiber hydrogel patches as a wearable biosensor via electrospinning

Micro- and nanofiber (NF) hydrogels fabricated by electrospinning to typically exhibit outstanding high porosity and specific surface area under hydrated conditions. However, the high crystallinity of NFs limits the achievement of transparency via electrospinning. Transparent poly(vinyl alcohol)/β-cyclodextrin polymer NF hydrogels contacted with reverse iontophoresis electrodes were prepared for the development of a non-invasive continuous monitoring biosensor platform of interstitial fluid glucose levels reaching ~ 1 mM. We designed the PVA/BTCA/β-CD/GOx/AuNPs NF hydrogels, which exhibit flexibility, biocompatibility, excellent absorptivity (DI water: 21.9 ± 1.9, PBS: 41.91 ± 3.4), good mechanical properties (dried: 12.1 MPa, wetted: 5.33 MPa), and high enzyme activity of 76.3%. Owing to the unique features of PVA/β-CD/GOx containing AuNPs NF hydrogels, such as high permeability to bio-substrates and rapid electron transfer, our biosensors demonstrate excellent sensing performance with a wide linear range, high sensitivity(47.2 μA mM−1), low sensing limit (0.01 mM), and rapid response time (< 15 s). The results indicate that the PVA/BTCA/β-CD/GOx/AuNPs NF hydrogel patch sensor can measure the glucose concentration in human serum and holds massive potential for future clinical applications.

Non-Invasive Extraction of Gabapentin for Therapeutic Drug Monitoring by Reverse Iontophoresis: Effect of pH, Ionic Strength, and Polyethylene Glycol 400 in the Receiving Medium

Background: Monitoring of plasma concentrations is a necessity for narrow therapeutic index potent drugs. Development of non-invasive methods can save the patients from the trauma of needles and hence is considered as a research priority. Introduction: Gabapentin, an anti-epileptic drug requires therapeutic monitoring because of its narrow therapeutic index. The objective of the study was to develop a suitable method for the non-invasive extraction of gabapentin for the same. Methods: Transdermal reverse iontophoresis was performed using pig ear skin as a barrier membrane. Three compartment iontophoretic cells were used for the extraction study. Extractions were carried out under low intensity electric field (current intensity- 0.5 mA/cm2, electrical field approximately 5 V). The donor compartment was charged with aqueous gabapentin (10 µg/ml in phosphate buffer of pH 7.4). For studying the effect of receiving vehicle (pH, ionic strength, and enhancer) on the extraction efficiency of gabapentin, the two receiver chambers were charged with media having varying concentration of these factors. Drug content was determined by HPLC. Results: Compared to other pHs, cumulative extraction of gabapentin at pH 5 was significantly higher at both anode and cathode (p<0.001). At low ionic strength, extraction of gabapentin increased linearly with the increase in concentration of ions up to a certain value but at very high ionic strength the pattern reversed. Similar results were obtained with enhancer (polyethylene glycol 400). Extraction increased with increase in polyethylene glycol 400 up to 3% and then decreased. Conclusion: Extraction flux can be optimized by manipulation of the receiver media.

Current Advancements in Transdermal Biosensing and Targeted Drug Delivery

In this manuscript, recent advancements in the area of minimally-invasive transdermal biosensing and drug delivery are reviewed. The administration of therapeutic entities through the skin is complicated by the stratum corneum layer, which serves as a barrier to entry and retards bioavailability. A variety of strategies have been adopted for the enhancement of transdermal permeation for drug delivery and biosensing of various substances. Physical techniques such as iontophoresis, reverse iontophoresis, electroporation, and microneedles offer (a) electrical amplification for transdermal sensing of biomolecules and (b) transport of amphiphilic drug molecules to the targeted site in a minimally invasive manner. Iontophoretic delivery involves the application of low currents to the skin as well as the migration of polarized and neutral molecules across it. Transdermal biosensing via microneedles has emerged as a novel approach to replace hypodermic needles. In addition, microneedles have facilitated minimally invasive detection of analytes in body fluids. This review considers recent innovations in the structure and performance of transdermal systems.

A cellulose/β-cyclodextrin nanofiber patch as a wearable epidermal glucose sensor

In this study, we aimed to develop a cellulose/β-cyclodextrin (β-CD) electrospun immobilized GOx enzyme patch with reverse iontophoresis for noninvasive monitoring of interstitial fluid (ISF) glucose levels (0.1–0.6 mM dm−3).