Transdermal iontophoretic delivery of bovine insulin and monomeric human insulin analogue

Kanikkannan, Narayanasamy; Singh, Jagdish; Ramarao, P.

doi:10.1016/s0168-3659(98)00184-9

Cited by 68 publications

(37 citation statements)

References 14 publications

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“…Induction of diabetes was performed as described previously (Kanikkannan et al, 1999). Briefly, a freshly prepared solution of streptozotocin (STZ) (Wako Pure Chemical, Osaka, Japan) (100 mg/kg) in 0.1 M citrate buffer, pH 4.4 was injected intraperitoneally.…”

Section: Experiments On Streptozotocin (Stz)-induced Diabetic Model Ratsmentioning

confidence: 99%

Noninvasive and persistent transfollicular drug delivery system using a combination of liposomes and iontophoresis

Kajimoto

Yamamoto

Watanabe

et al. 2011

International Journal of Pharmaceutics

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Iontophoresis is a promising technique for enhancing transdermal administration of charged drugs. However, conventional iontophoresis is not sufficient for effective delivery of large, hydrophilic, or electrically neutral molecules. In this study, we utilized charged liposomes as carriers, focused on a transfollicular route for delivery of the liposomes, and optimized iontophoretic conditions and lipid composition for this method in both in vitro and in vivo conditions.As a result, we identified the optimum condition (lipid composition:DOTAP/EPC/Chol=2:2:1, current supply: 0.45 mA/cm 2 , duration: 1 hr) for effective iontophoretic delivery of aqueous solution, which can not be transferred into the skin without charged liposomes. We also examined the pharmacological effects of iontophoresis of liposomes encapsulating insulin (INS-lipo) using a rat model of type I diabetes. Interestingly, iontophoresis of INS-lipo onto a diabetes rat skin resulted in a gradual decrease in blood glucose levels, with levels reaching 20% of initial values at 18 hr after administration. These lower blood glucose levels were maintained for up to 24 hr. Significant amount of insulin were also detected in plasma 18 hr after iontophoresis of INS-lipo. We succeeded in developing a non-invasive and persistent transfollicular drug delivery system that used a combination of liposomes and iontophoresis.

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Section: Experiments On Streptozotocin (Stz)-induced Diabetic Model Ratsmentioning

confidence: 99%

Noninvasive and persistent transfollicular drug delivery system using a combination of liposomes and iontophoresis

Kajimoto

Yamamoto

Watanabe

et al. 2011

International Journal of Pharmaceutics

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“…The insulin content of FhI-8, FhI-9 and FhI-10 and FhI-11 hybrids was monitored using eLISa over a period of 10 and 20 days (n = 3). Cell per well was defined as 10 6 and all experiments were carried out in triplicate. Insulin concentrations were given in μU/mL.…”

Section: Methodsmentioning

confidence: 99%

“…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%

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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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“…However, the percutaneous absorption of drugs with a high molecular weight and hydrophilic properties is not sufficient due to the barrier function of the skin. To enhance the absorption, several investigations using vehicles, 1,2) chemical enhancers, [3][4][5][6] iontophoresis, [7][8][9] electroporation 10,11) and phonophoresis 12,13) have been performed. We have focused on iontophoresis in terms of the enhancement of the amount of drug delivered by current with low skin irritation.…”

mentioning

confidence: 99%

Evaluation of Skin Barrier Function Using Direct Current III: Effects of Electrode Distance, Boundary Length and Shape

Kanebako¹,

Inagi²,

Takayama

2003

Biological & Pharmaceutical Bulletin

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Transdermal drug delivery can avoid first-pass metabolism, which is the greatest disadvantage of oral administration. However, the percutaneous absorption of drugs with a high molecular weight and hydrophilic properties is not sufficient due to the barrier function of the skin. To enhance the absorption, several investigations using vehicles, 1,2) chemical enhancers, [3][4][5][6] iontophoresis, 7-9) electroporation 10,11) and phonophoresis 12,13) have been performed. We have focused on iontophoresis in terms of the enhancement of the amount of drug delivered by current with low skin irritation. In a previous study, we predicted that the amount of drug that migrated in the skin was determined by a synergistic effect of both current application and enhanced passive diffusion due to the reduction in barrier function.14)The prediction was proved by the measurement of the distribution using indomethacin as a model drug. 15) In these studies, the accumulation of drug in the stratum corneum contributed to enhanced passive diffusion due to the reduction in barrier function. On the other hand, the accumulation from dermis to upper dermis was attributed to a passage of current. Further, a novel method for analyzing the reduction in barrier function under constant voltage was proposed.16) With this method, the barrier function was defined as resistance, which represented the sum of exponential functions of surface and skin resistance. In addition, the evaluation was carried out using the initial value and rate constant of the surface resistance. Using this method, effects of conductivity in the adhesive pad, voltage, the distance between electrodes and electrode area on the barrier function were evaluated. Furthermore, the influence of a pulsed direct current, which could prevent skin polarization and irritation was investigated. 17)The reduction in barrier function brought about by the application of sine and rectangular waveforms with a 75% duty cycle was almost the same as that caused by the application of direct current. Considering the skin polarization, the pulsed currents were more suitable.In the evaluation of changing electrode area, 16) although the initial value of surface resistance increased with increasing electrode area, no change of rate constant was observed. The rate constant showed the damping of the surface resistance, i.e., the barrier function. These phenomena contributed to the higher current density in the portion adjacent to the other electrode. Therefore, we investigated the electrode disposition and shape considering the reduction in barrier function as well as effective delivery of drugs into the skin. Similar results were reported by Haga et al. 18) They prepared electrodes with different boundary lengths using a photoeching technique, and then observed the skin distribution of 6-carboxyfluorescein (6-CF) under constant voltage. In that paper, the topical distribution of 6-CF in the skin was recognized in both boundary portions, i.e., the portion adjacent to the other electrode. They suggested ...

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Transdermal iontophoretic delivery of bovine insulin and monomeric human insulin analogue

Cited by 68 publications

References 14 publications

Noninvasive and persistent transfollicular drug delivery system using a combination of liposomes and iontophoresis

Noninvasive and persistent transfollicular drug delivery system using a combination of liposomes and iontophoresis

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

Evaluation of Skin Barrier Function Using Direct Current III: Effects of Electrode Distance, Boundary Length and Shape

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