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Pharmaceutics
Special Issues
Iontophoresis for Drug Delivery and Non-Invasive Sampling Applications
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Iontophoresis for Drug Delivery and Non-Invasive Sampling Applications

A special issue of Pharmaceutics (ISSN 1999-4923).

Deadline for manuscript submissions: closed (30 September 2018) | Viewed by 50454

Special Issue Editors

Prof. Dr. Maria Begoña Delgado-Charro

E-Mail Website
Guest Editor
Department of Life Sciences, University of Bath, Claverton Down, Bath BA2 7AY, UK
Interests: topical drug delivery; transdermal drug delivery; nail drug delivery; bioequivalence; regulatory science; onychomychosis
Special Issues, Collections and Topics in MDPI journals
Dr. Virginia Merino Sanjuán

E-Mail Website
Guest Editor
Department of Pharmacy and Pharmaceutical Technology and Parasitology, School of Pharmacy, University of Valencia, Valencia, Spain
Interests: pharmacokinetics; biopharmaceutics; oral absorption; topical formulations; in vitro release
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Iontophoresis is a versatile technique used for controlled drug delivery and non-invasive sampling applications. This drug delivery strategy has been exploited to increase and control the passage of molecules through biological membranes with applications in the transdermal, topical, ocular, dental, trans-ungueal and trans-mucosal routes of administration. Significant progress has improved our understanding of the mechanisms of transport and the design of efficient iontophoretic vehicles. Non-invasive sampling applications target the skin interface primarily. Several iontophoretic devices have gone through regulatory approval but demonstrated limited commercial success.

This Special Issue will gather current progress in the iontophoresis field and critically evaluate what is the place of this technique in the future therapeutic armamentarium and what is required to better exploit iontophoresis for the benefit of patients.

We invite articles from academics, industry and clinical researchers on all aspects of iontophoresis, from basic principles and theoretical modelling to basic and clinical research.

Dr. M. Begoña Delgado-Charro
Prof. Virginia Merino Sanjuán
Guest Editors

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Keywords

  • Iontophoresis
  • transdermal
  • ocular
  • non-invasive sampling
  • controlled drug delivery
  • electro-osmosis
  • electrorepulsion
  • nail-delivery
  • dental-delivery

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Published Papers (7 papers)

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Research

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11 pages, 1388 KiB  
Article
Investigation of Different Iontophoretic Currents Profiles for Short-Term Applications in Cosmetics
by Jennyfer Cázares-Delgadillo, Lien Planard-Luong, Sébastian Gregoire, César E. Serna-Jiménez, Mayank Singhal, Yogeshvar N. Kalia, Virginia Merino, Matilde Merino-Sanjuán, Amparo Nácher, Ma. Amparo Martínez-Gómez, Veronique Burnier-Yalaoui and Philippe Barbarat
Pharmaceutics 2018, 10(4), 266; https://doi.org/10.3390/pharmaceutics10040266 - 7 Dec 2018
Cited by 6 | Viewed by 5926
Abstract
This study aimed at investigating the effect of electrical current profile upon the iontophoretic transport of (i) ascorbic acid (AA) and (ii) ellagic acid (EA), into porcine skin in vitro, and the impact of the physicochemical properties of both actives on their mechanism [...] Read more.
This study aimed at investigating the effect of electrical current profile upon the iontophoretic transport of (i) ascorbic acid (AA) and (ii) ellagic acid (EA), into porcine skin in vitro, and the impact of the physicochemical properties of both actives on their mechanism of transport when formulated in cosmetic compositions. The experiments were performed using a proprietary iontophoretic device containing a roller to apply the formulation. Three current profiles were tested: (i) galvanic direct current (DC), (ii) square unipolar pulse current (SPC), and (iii) galvanic direct current (DC) + pulse current (PC). The skin samples were collected at different sampling points, extracted and analyzed by HPLC. Results suggested that the DC + PC mode for only 5 min was able to significantly increase the delivery of AA from o/w cosmetic compositions. The use of this current profile might improve the skin penetration of AA due to electromigration and passive diffusion, the latter being facilitated by the physical enhancement method. The SPC mode significantly improved the passage of EA in its neutral form from cosmetic o/w formulations by electroosmosis. Tailoring specific electrical current modes considering the ionization state of active ingredients would allow the design of short and personalized cosmetic treatments that significantly improve the penetration efficiency of the active ingredients and possibly reduce the doses applied. Full article
(This article belongs to the Special Issue Iontophoresis for Drug Delivery and Non-Invasive Sampling Applications)
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15 pages, 1345 KiB  
Article
Influence of Chemical Enhancers and Iontophoresis on the In Vitro Transdermal Permeation of Propranolol: Evaluation by Dermatopharmacokinetics
by María Aracely Calatayud-Pascual, María Sebastian-Morelló, Cristina Balaguer-Fernández, M. Begoña Delgado-Charro, Alicia López-Castellano and Virginia Merino
Pharmaceutics 2018, 10(4), 265; https://doi.org/10.3390/pharmaceutics10040265 - 7 Dec 2018
Cited by 20 | Viewed by 6060
Abstract
The aims of this study were to assess, in vitro, the possibility of administering propranolol transdermally and to evaluate the usefulness of the dermatopharmacokinetic (DPK) method in assessing the transport of drugs through stratum corneum, using propranolol as a model compound. Four chemical [...] Read more.
The aims of this study were to assess, in vitro, the possibility of administering propranolol transdermally and to evaluate the usefulness of the dermatopharmacokinetic (DPK) method in assessing the transport of drugs through stratum corneum, using propranolol as a model compound. Four chemical enhancers (decenoic and oleic acid, laurocapram, and R-(+)-limonene) and iontophoresis at two current densities, 0.25 and 0.5 mA/cm2 were tested. R-(+)-limonene, and iontophoresis at 0.5 mA/cm2 were proven to be the most efficient in increasing propranolol transdermal flux, both doubled the original propranolol transdermal flux. Iontophoresis was demonstrated to be superior than the chemical enhancer because it allowed faster delivery of the drug. The DPK method was sufficiently sensitive to detect subtle vehicle-induced effects on the skin permeation of propranolol. The shorter duration of these experiments and their ability to provide mechanistic information about partition between vehicle and skin and diffusivity through skin place them as practical and potentially insightful approach to quantify and, ultimately, optimize topical bioavailability. Full article
(This article belongs to the Special Issue Iontophoresis for Drug Delivery and Non-Invasive Sampling Applications)
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18 pages, 3898 KiB  
Article
Nanoemulsion as a Platform for Iontophoretic Delivery of Lipophilic Drugs in Skin Tumors
by Luciana Facco Dalmolin and Renata F. V. Lopez
Pharmaceutics 2018, 10(4), 214; https://doi.org/10.3390/pharmaceutics10040214 - 4 Nov 2018
Cited by 27 | Viewed by 5420
Abstract
Lipophilic drugs do not usually benefit from iontophoresis mainly because they do not solubilize in aqueous formulations suitable for the application of electric current. To explore the influence of iontophoresis on penetration of these drugs, a cationic nanoemulsion was developed to solubilize zinc [...] Read more.
Lipophilic drugs do not usually benefit from iontophoresis mainly because they do not solubilize in aqueous formulations suitable for the application of electric current. To explore the influence of iontophoresis on penetration of these drugs, a cationic nanoemulsion was developed to solubilize zinc phthalocyanine (ZnPc), a promising drug for the treatment of skin cancer. To verify the influence of particle size on iontophoresis, an emulsion of nanoemulsion-like composition was also developed. The formulations were characterized and cutaneous and tumor penetration studies were performed in vitro and in vivo, respectively. With particles of about 200 nm, the nanoemulsion solubilized 2.5-fold more ZnPc than the 13-µm emulsion. At the same concentration of ZnPc, in vitro passive penetration studies showed that the nanoemulsion increased, after 1 h of treatment, by almost 4 times the penetration of ZnPc into the viable layers of the skin when compared to the emulsion, whereas iontophoresis of nanoemulsion resulted in a 16-fold increase in ZnPc penetration in only 30 min. An in vivo study in a murine model of melanoma showed that ZnPc reached the tumor after iontophoresis of the nanoemulsion. Therefore, iontophoresis of nanoemulsions appears to be a promising strategy for the topical treatment of tumors with lipophilic drugs. Full article
(This article belongs to the Special Issue Iontophoresis for Drug Delivery and Non-Invasive Sampling Applications)
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11 pages, 3281 KiB  
Article
Iontophoretic Transdermal Delivery of Human Growth Hormone (hGH) and the Combination Effect of a New Type Microneedle, Tappy Tok Tok®
by Gyubin Noh, Taekwang Keum, Jo-Eun Seo, Santosh Bashyal, Nyeon-Sik Eum, Min Jung Kweon, Sooyeun Lee, Dong Hwan Sohn and Sangkil Lee
Pharmaceutics 2018, 10(3), 153; https://doi.org/10.3390/pharmaceutics10030153 - 7 Sep 2018
Cited by 26 | Viewed by 6538
Abstract
Transdermal drug administration presents several advantages and it is therefore favorable as an alternative drug delivery route. However, transdermal delivery of biopharmaceutical drugs is made difficult by the skin barrier. Microneedle application and iontophoresis are strategies which can be used to overcome this [...] Read more.
Transdermal drug administration presents several advantages and it is therefore favorable as an alternative drug delivery route. However, transdermal delivery of biopharmaceutical drugs is made difficult by the skin barrier. Microneedle application and iontophoresis are strategies which can be used to overcome this barrier. Therefore, recombinant human growth hormone (rhGH) was used as a model macromolecular drug and was transdermally delivered using microneedle application and iontophoresis. Methylene blue staining, stereomicroscopy and scanning electron microscope (SEM) imaging were used to characterize the microchannels produced. To optimize the iontophoresis protocol, the effects of molecular charge and current density on transdermal delivery were evaluated in an in vitro permeation study using excised rat skin tissues. Using the optimized iontophoresis protocol, the combination effects of iontophoretic delivery via microchannels were evaluated in three different experimental designs. The flux obtained with anodal iontophoresis in citrate buffer was approximately 10-fold higher that that with cathodal iontophoresis in phosphate buffered saline (PBS). Flux also increased with current density in anodal iontophoresis. The combination of iontophoresis and microneedle application produced higher flux than single application. These results suggest that anodal iontophoresis with higher current density enhances the permeation of macromolecules through microchannels created by microneedles. In conclusion, the combination of iontophoresis and microneedles is a potential strategy for the enhancement of transdermal delivery of macromolecular drugs. Full article
(This article belongs to the Special Issue Iontophoresis for Drug Delivery and Non-Invasive Sampling Applications)
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18 pages, 1872 KiB  
Article
Electrically and Ultrasonically Enhanced Transdermal Delivery of Methotrexate
by Hiep X. Nguyen and Ajay K. Banga
Pharmaceutics 2018, 10(3), 117; https://doi.org/10.3390/pharmaceutics10030117 - 5 Aug 2018
Cited by 40 | Viewed by 6368
Abstract
In this study, we used sonophoresis and iontophoresis to enhance the in vitro delivery of methotrexate through human cadaver skin. Iontophoresis was applied for 60 min at a 0.4 mA/sq·cm current density, while low-frequency sonophoresis was applied at a 20 kHz frequency (2 [...] Read more.
In this study, we used sonophoresis and iontophoresis to enhance the in vitro delivery of methotrexate through human cadaver skin. Iontophoresis was applied for 60 min at a 0.4 mA/sq·cm current density, while low-frequency sonophoresis was applied at a 20 kHz frequency (2 min application, and 6.9 W/sq·cm intensity). The treated skin was characterized by dye binding, transepidermal water loss, skin electrical resistance, and skin temperature measurement. Both sonophoresis and iontophoresis resulted in a significant reduction in skin electrical resistance as well as a marked increase in transepidermal water loss value (p < 0.05). Furthermore, the ultrasonic waves resulted in a significant increase in skin temperature (p < 0.05). In permeation studies, the use of iontophoresis led to a significantly higher drug permeability than the untreated group (n = 4, p < 0.05). The skin became markedly more permeable to methotrexate after the treatment by sonophoresis than by iontophoresis (p < 0.01). A synergistic effect for the combined application of sonophoresis and iontophoresis was also observed. Drug distribution in the skin layers revealed a significantly higher level of methotrexate in the sonicated skin than that in iontophoresis and untreated groups. Iontophoresis and low-frequency sonophoresis were found to enhance the transdermal and intradermal delivery of methotrexate in vitro. Full article
(This article belongs to the Special Issue Iontophoresis for Drug Delivery and Non-Invasive Sampling Applications)
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Review

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13 pages, 438 KiB  
Review
Selected Medicines Used in Iontophoresis
by Tomasz M. Karpiński
Pharmaceutics 2018, 10(4), 204; https://doi.org/10.3390/pharmaceutics10040204 - 25 Oct 2018
Cited by 48 | Viewed by 9857
Abstract
Iontophoresis is a non-invasive method of systemic and local drug delivery using an electric field. Iontophoresis enables diffusion of the selected drug via skin, mucosa, enamel, dentin, and other tissues. The amount of delivered therapeutic molecules is about 10–2000 times greater than conventional [...] Read more.
Iontophoresis is a non-invasive method of systemic and local drug delivery using an electric field. Iontophoresis enables diffusion of the selected drug via skin, mucosa, enamel, dentin, and other tissues. The amount of delivered therapeutic molecules is about 10–2000 times greater than conventional forms of delivery. Among other fields, this method is used in dentistry, ophthalmology, otorhinolaryngology, and dermatology. According to related literature, the most important drugs studied or administered by iontophoresis are: Local anesthetics, opioids, steroids, non-steroidal anti-inflammatory drugs, antibacterial drugs, antifungal drugs, antiviral drugs, anticancer drugs, fluorides, and vitamins. The present review covers current available data regarding the selected medicines used in iontophoresis. Furthermore, indications and conditions of iontophoresis application are reviewed. Full article
(This article belongs to the Special Issue Iontophoresis for Drug Delivery and Non-Invasive Sampling Applications)
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17 pages, 1218 KiB  
Review
Iontophoretic Drug Delivery in the Oral Cavity
by Apipa Wanasathop and S. Kevin Li
Pharmaceutics 2018, 10(3), 121; https://doi.org/10.3390/pharmaceutics10030121 - 7 Aug 2018
Cited by 29 | Viewed by 8445
Abstract
Iontophoresis is a noninvasive method to enhance systemic and local drug delivery by the application of an electric field. For systemic drug delivery in the oral cavity, iontophoresis was studied primarily for transbuccal delivery. Significant enhancement of drug delivery was observed in buccal [...] Read more.
Iontophoresis is a noninvasive method to enhance systemic and local drug delivery by the application of an electric field. For systemic drug delivery in the oral cavity, iontophoresis was studied primarily for transbuccal delivery. Significant enhancement of drug delivery was observed in buccal iontophoresis compared to passive transport for different drugs. For local drug delivery in the oral cavity, iontophoresis could enhance drug penetration into the enamel, dentin, and other oral tissues for the treatment of oral diseases. Iontophoresis was evaluated in dentistry such as to produce local anesthesia and treat tooth decalcification and hypersensitivity, but this technology has not been fully utilized. The most common drugs in these evaluations were fluoride and lidocaine. In general, there is limited knowledge of the mechanisms of iontophoresis in the oral tissues. In vivo animal and human studies have suggested that iontophoresis is safe in the oral cavity under the conditions investigated. The present review covers the topics of iontophoretic drug delivery in the oral cavity for both systemic and local treatments. The anatomy and diseases in the oral cavity for iontophoretic drug delivery are also briefly reviewed, and the challenges for this drug delivery method are discussed. Full article
(This article belongs to the Special Issue Iontophoresis for Drug Delivery and Non-Invasive Sampling Applications)
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