Topical iodine facilitates transdermal delivery of insulin

Department of Clinical Pharmacology and School of Pharmacy, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel.
Journal of Controlled Release (Impact Factor: 7.71). 05/2007; 118(2):185-8. DOI: 10.1016/j.jconrel.2006.12.006
Source: PubMed


Transdermal delivery of insulin is a non-invasive alternative to the subcutaneous injection of insulin in diabetic patients. It has been found that skin pretreatment with iodine followed by a dermal application of insulin results in reduced glucose and elevated hormone levels in the plasma. Topical iodine protects the dermally applied insulin presumably by inactivation of endogenous sulfhydryls such as glutathione and gamma glutamylcysteine which can reduce the disulfide bonds of the hormone. Thus, the effect of iodine is mediated by retaining the potency of the hormone during its penetration via the skin into the circulation. The proposed procedure might be applicable for additional disulfide-containing peptides such as calcitonin, somatostatin, oxytocin/vasopressin and their analogs.

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    • "To limit these drawbacks , transdermal route for insulin delivery as an alternative non-parenteral route of administration can be used to treat diabetic patients. During the past few years, various experimental methodologies have been successfully developed for facilitating transdermal delivery of insulin (Sen et al., 2002; Pillai et al., 2003; Amnon and Wormser, 2007; Cevc, 2003; King et al., 2002). "
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    ABSTRACT: The present study deals with the development of transferosomal gel containing insulin by reverse phase evaporation method for painless insulin delivery for use in the treatment of insulin dependent diabetes mellitus. The effect of independent process variables like ratio of lipids (soya lecithin:cholesterol), ratio of lipids and surfactants, and ratio of surfactants (Tween 80:sodium deoxycholate) on the in vitro permeation flux (μg/cm(2)/h) of formulated transferosomal gels containing insulin through porcine ear skin was optimized using 2(3) factorial design. The optimal permeation flux was achieved as 13.50 ± 0.22 μg/cm(2)/h with drug entrapment efficiency of 56.55 ± 0.37% and average vesicle diameter range, 625-815 nm. The in vitro insulin permeation through porcine ear skin from these transferosomal gel followed zero-order kinetics (R (2) = 0.9232-0.9989) over a period of 24 h with case-II transport mechanism. The in vitro skin permeation of insulin from optimized transferosomal gel by iontophoretic influence (with 0.5 mA/cm(2) current supply) also provided further enhancement of permeation flux to 17.60 ± 0.03 μg/cm(2)/h. The in vivo study of optimized transferosomal gel in alloxan-induced diabetic rat has demonstrated prolonged hypoglycemic effect in diabetic rats over 24 h after transdermal administration.
    Saudi Pharmaceutical Journal 10/2012; 20(4):355-63. DOI:10.1016/j.jsps.2012.02.001 · 1.28 Impact Factor
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    • "Priborsky et al. (Priborsky et al., 1988) studied the effects of CPEs without using any physical methods, but the number of CPEs investigated was limited to three. Similar studies on a handful of CPEs have been carried out by others (Rastogi and Singh, 2003, Sintov and Wormser, 2007). This literature review suggests that there is a serious shortage of insulin permeability data in the presence of different CPE classes. "
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    ABSTRACT: Enhancing transdermal delivery of insulin using chemical penetration enhancers (CPEs) has several advantages over other non-traditional methods; however, lack of suitable predictive models, make experimentation the only alternative for discovering new CPEs. To address this limitation, a quantitative structure–property relationship (QSPR) model was developed, for predicting insulin permeation in the presence of CPEs. A virtual design algorithm that incorporates QSPR models for predicting CPE properties was used to identify 48 potential CPEs. Permeation experiments using Franz diffusion cells and resistance experiments were performed to quantify the effect of CPEs on insulin permeability and skin structure, respectively. Of the 48 CPEs, 35 were used for training and 13 were used for validation. In addition, 12 CPEs reported in literature were also included in the validation set. Differential evolution (DE) was coupled with artificial neural networks (ANNs) to develop the non-linear QSPR models. The six-descriptor model had a 16% absolute average deviation (%AAD) in the training set and 4 misclassifications in the validation set. Five of the six descriptors were found to be statistically significant after sensitivity analyses. The results suggest, molecules with low dipoles that are capable of forming intermolecular bonds with skin lipid bi-layers show promise as effective insulin-specific CPEs.
    International Journal of Pharmaceutics 12/2009; 388(1-2-388):13-23. DOI:10.1016/j.ijpharm.2009.12.028 · 3.65 Impact Factor
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    • "In one study, the pharmacological availability of insulin delivered by drug-loaded polymer microneedles was found to be between 91 and 98% when compared to intravenous dosing. In many practical cases, it may be possible to prevent metabolism, as demonstrated by Sintov and Wormser (2007). Iodine was used to deactivate skin glutathione so that insulin could retain its potency as it permeated through. "
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    ABSTRACT: This article was published in the journal, Chemical Engineering Research and Design [Elsevier / © The Institution of Chemical Engineers] and the definitive version is available at: Although transdermal drug delivery has been used for about three decades, the range of therapeutics that are administered this way is limited by the barrier function of the stratum corneum (the top layer of skin). Microneedle arrays have been shown to increase the drug permeability in skin by several orders of magnitude by bypassing the stratum corneum. This 15 can potentially allow the transdermal delivery of many medicaments including large macromolecules that typically cannot diffuse through the skin. This paper addresses the use of microneedles coated with a drug solution film. In particular, we identify how the geometries of various microneedles affect the drug permeability in skin. Effective skin permeability is calculated for a range of microneedle shapes and dimensions in order to identify the most 20 efficient geometry. To calculate effective permeability (Peff), the effective skin thickness (Heff) is calculated. These are then plotted for insulin as a model drug to see how various microneedle parameters affect the profiles of both Heff and Peff. It is found that the depth of penetration from the microneedle array is the most important factor in determining Peff, followed by the microneedle spacings. Other parameters such as microneedle diameter and 25 coating depth are less significant. Accepted for publication
    Chemical Engineering Research and Design 11/2008; 86(11A). DOI:10.1016/j.cherd.2008.06.002 · 2.28 Impact Factor
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