Transdermal Iontophoretic Delivery of Therapeutic Peptides/Proteins I: Insulin

Chien, Yie W.; Siddiqui, Ovais; Sun, Yi-Ming; Shi, Weimin; Liu, J. C.

doi:10.1111/j.1749-6632.1987.tb45790.x

Cited by 89 publications

(26 citation statements)

References 32 publications

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“…Data obtained from [28] Transdermal iontophoretic transport of normal, hexameric insulin through rodent skin in vitro has been reported to be very low [31] and far from clinically relevant. Several in vivo experiments with transdermal, iontophoretic delivery into diabetic pigs, rabbits and hairless rats have been reported [32][33][34][35][36][37][38] using variable current densities, formulation and polarity. Stephen et al [32] could not detect any effect after cathodal iontophoresis of porcine (hexameric) insulin, whereas with a monomeric, highly ionized sulphated insulin therapeutic plasma hormone levels were obtained in a single diabetic pig.…”

Section: Insulins For Transdermal Delivery By Iontophoresismentioning

confidence: 99%

“…Stephen et al [32] could not detect any effect after cathodal iontophoresis of porcine (hexameric) insulin, whereas with a monomeric, highly ionized sulphated insulin therapeutic plasma hormone levels were obtained in a single diabetic pig. Systemic insulin delivery to rats has been studied by Chien and coworkers [34][35][36]. Based on the reduction in blood glucose, enhanced iontophoretic transport was reported of positively charged, and less aggregated insulin at pH 3.6 as compared to negatively charged, hexameric insulin at neutral pH.…”

Section: Insulins For Transdermal Delivery By Iontophoresismentioning

confidence: 99%

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The new era of biotech insulin analogues

Brange

1997

Diabetologia

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The introduction of insulin in the 1920 s revolutionized the treatment of diabetes mellitus. However, pancreatic insulin did not evolve for exogenous administration, and subcutaneous injection therapy has not succeeded in normalizing glycaemic control despite the great efforts devoted to improvements in insulin preparations and injection regimens. The increasing awareness and acceptance of the relationship between metabolic control and the occurrence of devastating microvascular complications have stimulated considerable research into new methods of improving insulin therapy.In the field of pharmaceutical formulation important improvements have emerged. However, the pharmacokinetics following subcutaneous injection of the currently available rapid-, intermediate-and long-acting insulin preparations make it virtually impossible to achieve normoglycaemia. The absorption of insulin from the injection site is a complex process affected by many factors, such as location of the site, physical state of the patient and the nature of the insulin preparation. After subcutaneous injection of regular insulin into the femoral region it takes 2-4 h for the insulin to be absorbed at maximum rate. This slow rise to peak insulin concentration is likely to account for much of the observed postprandial hyperglycaemia seen in diabetic subjects. As the insulin concentration falls slowly after the peak, the extended period of elevated insulin concentration results in a tendency towards late hypoglycaemia. Such plasma insulin patterns bear no resemblance to those in normal subjects in response to a meal. After subcutaneous injection of soluble insulin an initial phase (lag phase) with low but increasing relative rate of absorption has been observed in most clinical studies. This initial delay in absorption is shortened or even disappears when reducing the concentration of insulin or decreasing the volume injected [1].Until recently advances in insulin formulation were limited to improvements in insulin purity, insulin Diabetologia (1997) 40: S 48-S 53 The new era of biotech insulin analogues J. BrangeNovo Nordisk A/S, Bagsvaerd, Denmark © Springer-Verlag 1997Corresponding author: Dr. J. Brange, Novo Nordisk A/S, Building 6A, Novo Alle, DK-2880 Bagsvaerd, Denmark Summary Many of the structural properties of insulin have evolved in response to the requirements of biosynthesis, processing, transport and storage in the pancreatic beta cells, properties that are not necessary for the biological action of the hormone. It is therefore not surprising that wild-type insulin has far from optimal characteristics for replacement therapy. For example, native human insulin self-associates to hexameric units, which limits the possibilities for the absorption of the molecule by various routes. During the last decade new techniques of molecular design have emerged and recombinant DNA technology offers new and exciting opportunities for rational protein drug design. This review describes examples of recent advances in insulin engineering aimed at op...

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Section: Insulins For Transdermal Delivery By Iontophoresismentioning

confidence: 99%

Section: Insulins For Transdermal Delivery By Iontophoresismentioning

confidence: 99%

The new era of biotech insulin analogues

Brange

1997

Diabetologia

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“…Many of the acute effects of this T1DM can, however, be controlled by insulin replacement therapy, which in recent times has come in the form of: (1) transdermal approach, [5][6][7] (2) pulmonary approach, [8][9][10][11] (3) oral approach 12,13 and (4) intranasal approach. 14,15 In addition, pancreatic transplantation has been used clinically since the 1960s 16 and is now being performed in increasing numbers.…”

Section: Introductionmentioning

confidence: 99%

“…Despite several attempts to provide alternative regimens to insulin therapy [5][6][7]14,22,23 for the debilitating sequelae of T1DM, there exists no present day panacea. Even the most recent successes of islet transplantation depends upon the number of islets transplanted to each patient.…”

Section: Introductionmentioning

confidence: 99%

Characterisation of the NES2Y cell line and its use in the production of human glucose-responsive insulin producing (hGRIP) cell lines by cell-cell fusion

Adams

Uddin²,

Vives-Pi³

et al. 2009

Islets

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“…This process, which disrupts local pH values, leads to stinging and erythrema (Howard et al 1995). The use of pulsed DC, (a constant DC delivered periodically), has been suggested to prevent charge build up on the skin (polarization) and minimize pH changes (Chien et al 1987;Chien et al 1990). Polarization effects turn the skin into what is effectively a charged capacitor and this reduces the fl ow of current and charged species during iontophoresis.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous transdermal extraction of glucose and lactate from human subjects by reverse iontophoresis

Connolly¹

2008

IJN

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This study investigated the possibility of simultaneously extracting glucose and lactate from human subjects, at the same skin location, using transdermal reverse iontophoresis. Transdermal monitoring using iontophoresis is made possible by the skin's permeability to small molecules and the nanoporous and microporous nature of the structure of skin. The study was intended to provide information which could be used to develop a full, biosensor-based, monitoring system for multiple parameters from transdermal extraction. As a precursor to the human study, in vitro reverse iontophoresis experiments were performed in an artifi cial skin system to establish the optimum current waveforms to be applied during iontophoresis. In the human study, a bipolar DC current waveform (with reversal of the electrode current direction every 15 minutes) was applied to ten healthy volunteers via skin electrodes and utilized for simultaneous glucose and lactate transdermal extraction at an applied current density of 300 µA/cm 2 . Glucose and lactate were successfully extracted through each subject's skin into the conducting gel that formed part of each iontophoresis electrode. The results suggest that it will be possible to noninvasively and simultaneously monitor glucose and lactate levels in patients using this approach and this could have future applications in diagnostic monitoring for a variety of medical conditions.

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Transdermal Iontophoretic Delivery of Therapeutic Peptides/Proteins I: Insulin

Cited by 89 publications

References 32 publications

The new era of biotech insulin analogues

The new era of biotech insulin analogues

Characterisation of the NES2Y cell line and its use in the production of human glucose-responsive insulin producing (hGRIP) cell lines by cell-cell fusion

Simultaneous transdermal extraction of glucose and lactate from human subjects by reverse iontophoresis

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