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Marro, Diego; Kalia, Yogeshvar N.; Delgado‐Charro, M. Begoña; Guy, Richard H.

doi:10.1023/a:1013370529366

Cited by 42 publications

(5 citation statements)

References 2 publications

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“…Application of an electric current dramatically increased the flux of both molecules even though the computation of transport numbers indicated that >99% of the charge was carried by TrisH+ from the buffer solution and subdermal chloride ions (transport numbers of NTX and BUP at pH 6 were 8.2 × 10 –4 and 4.5 × 10 –4 , respectively). This was expected and consistent with previous findings. , Importantly, the therapeutic target flux for BUP was achieved by iontophoresis.…”

Section: Resultssupporting

confidence: 89%

Simultaneous Transdermal Delivery of Buprenorphine Hydrochloride and Naltrexone Hydrochloride by Iontophoresis

et al. 2019

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The opioids buprenorphine hydrochloride (BUP) and naltrexone hydrochloride (NTX) show promise as a combination treatment for addiction, but no means of delivering the two compounds in one medicine currently exist. In this paper, we report sufficient input rates of both these drugs from one iontophoretic transdermal drug delivery system. Experiments were performed using dermatomed pig skin mounted in glass side-bi-side cells. BUP and NTX were iontophoretically delivered together from the anode using direct constant current from Ag/AgCl electrodes. The transdermal drug fluxes and the masses of drugs in both the stratum corneum and the underlying epidermis/dermis were measured. The apparent electroosmotic flow was quantified using a neutral marker (acetaminophen). The effects of donor composition (drug concentration/molar fraction and pH), current density and profile, and the choice of receptor solution were assessed. Iontophoresis dramatically increased the flux of both drugs compared to passive control values. Target fluxes (calculated from literature clearance values and required therapeutic plasma concentrations) were greatly exceeded for NTX and were met for BUP. The latter accumulated in the skin and suppressed electroosmotic flow, inhibiting both its own flux and that of NTX. NTX, in turn, negatively influenced the flux of BUP via co-ion competition. Lowering current density by increasing the delivery area resulted in increased electroosmotic flow but did not significantly affect current-normalized drug fluxes. Delivering the drugs from both electrodes and reversing the polarity for every 2 h did not increase the flux of either compound. In summary, during iontophoresis, BUP and NTX inhibited each other’s flux by two distinct mechanisms. While the more complex behavior of BUP complicates the optimization of this drug combination, iontophoresis nevertheless appears to be a feasible approach for the controlled codelivery of NTX and BUP through the skin.

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Section: Resultssupporting

confidence: 89%

Simultaneous Transdermal Delivery of Buprenorphine Hydrochloride and Naltrexone Hydrochloride by Iontophoresis

et al. 2019

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“…First, it is predictably altered by the ionic mole fraction, observations which have also been reported in transdermal iontophoresis. 37, 38 Importantly this provides a way to modify or predict changes in the ejection rate of a target ion. Secondly, the calculated transport number systematically underestimated the observed values, as larger quantities of DA were ejected than predicted from migration.…”

Section: Resultsmentioning

confidence: 99%

Quantitative analysis of iontophoretic drug delivery from micropipettes

Kirkpatrick

Walton

Edwards

et al. 2016

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Microiontophoresis is a drug delivery method in which an electric current is used to eject molecular species from a micropipette. It has been primarily utilized for neurochemical investigations, but is limited due to difficulty controlling and determining the ejected quantity. Consequently the concentration of an ejected species and the extent of the affected region are relegated to various methods of approximation. To address this, we investigated the principles underlying ejection rates and examined the concentration distribution in microiontophoresis using a combination of electrochemical, chromatographic, and fluorescence-based approaches. This involved a principal focus on how the iontophoretic barrel solution affects ejection characteristics. The ion ejection rate displayed a direct correspondence to the ionic mole fraction, regardless of the ejection current polarity. In contrast, neutral molecules are ejected by electroosmotic flow (EOF) at a rate proportional to the barrel solution concentration. Furthermore, the presence of EOF was observed from barrels containing high ionic strength solutions. In practice, use of a retaining current draws extracellular ions into the barrel and will alter the barrel solution composition. Even in the absence of a retaining current, diffusional exchange at the barrel tip will occur. Thus behavior of successive ejections may slightly differ. To account for this, electrochemical or fluorescence markers can be incorporated into the barrel solution in order to compare ejection quantities. These may also be used to provide an estimate of the ejected amount and distribution provided accurate use of calibration procedures.

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“…Molecular transport mechanisms in individual pores (e.g., protein ion channels and synthetic channels , ) and in materials containing pores of nanometer dimensions (e.g., zeolite catalysts and skin) are of interest throughout chemistry and biology. It is generally recognized that transport selectivity, based on a chemical or physical property of the permeant, is often observed in pores when the size of the pore is sufficiently small that interactions between the pore surface and permeant influence local transport dynamics.…”

Section: Introductionmentioning

confidence: 99%

Electrostatic-Gated Transport in Chemically Modified Glass Nanopore Electrodes

et al. 2006

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Electrostatic-gated transport in chemically modified glass nanopore electrodes with orifice radii as small as 15 nm is reported. A single conical-shaped nanopore in glass, with a approximately 1 microm radius Pt disk located at the pore base, is prepared by etching the exposed surface of a glass-sealed Pt nanodisk. The electrochemical response of the nanopore electrode corresponds to diffusion of redox-active species through the nanopore orifice to the Pt microdisk. Silanization of the exterior glass surface with Cl(Me)(2)Si(CH(2))(3)CN and the interior pore surface with EtO(Me)(2)Si(CH(2))(3)NH(2) introduces pH-dependent ion selectivity at the pore orifice, a consequence of the electrostatic interactions between the redox ions and protonated surface amines. Nanopore electrodes with very small pore orifice radii (< approximately 50 nm) display anion permselectively at pH < 4, as demonstrated by electrochemical measurement of transport through the pore orifice. Ion selective transport vanishes at pH > 6 or when the pore radius is significantly larger than the Debye screening length, consistent with the observed ion selectivity resulting from electrostatic interactions. The ability to introduce different surface functionalities to the interior and exterior surfaces of glass nanopores is demonstrated using fluorescence microscopy to monitor the localized covalent attachment of 5- (and 6)-carboxytetramethylrhodamine succinimidyl ester to interior pore surfaces previously silanized with EtO(Me)(2)Si(CH(2))(3)NH(2).

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Cited by 42 publications

References 2 publications

Simultaneous Transdermal Delivery of Buprenorphine Hydrochloride and Naltrexone Hydrochloride by Iontophoresis

Simultaneous Transdermal Delivery of Buprenorphine Hydrochloride and Naltrexone Hydrochloride by Iontophoresis

Quantitative analysis of iontophoretic drug delivery from micropipettes

Electrostatic-Gated Transport in Chemically Modified Glass Nanopore Electrodes

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