Transdermal iontophoresis of insulin

Pillai, Omathanu; Borkute, S. D.; Sivaprasad, N.; Panchagnula, Ramesh

doi:10.1016/s0378-5173(03)00034-6

Cited by 45 publications

(6 citation statements)

References 25 publications

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“…Many studies showed no significant effect of insulin concentration (0.2-10 mg/ml) on PGL reduction in diabetic rats. 8,37) In the present study, we confirmed that the size distribution (3.3-5.0 nm) was similar for 62.5 U/ml and 125 U/ml of insulin solutions, which could correspond to the permeability of insulin through the skin. On the other hand, we observed a concentration-dependent effect of trypsin on PGL reduction by insulin.…”

supporting

confidence: 84%

Transdermal Delivery of Insulin Using Trypsin as a Biochemical Enhancer

Quan

Zang

et al. 2008

Biological & Pharmaceutical Bulletin

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There are 30 million patients with diabetes mellitus worldwide, and 1.2 million new patients are diagnosed each year, including a growing number of children and young adults. 1)However, insulin has been administered only by parenteral routes for the therapeutic control of type 1 diabetes; many patients typically require injections of insulin a minimum of two to three times per day. To improve patient convenience and compliance, alternative routes have been investigated including nasal, oral, transdermal, buccal, ocular, rectal, and vaginal pathways. 2) Transdermal delivery of insulin can prevent its metabolization and the first-pass effect and may thus be an optimal route of administration. However, delivery of large molecules by the transdermal route is also limited by the unique bioarchitecture of skin, which has primarily evolved as a protective barrier against the entry of microorganisms and water.3)The stratum corneum (SC) barrier can be partially overcome by disruption of the lipid structure using fatty acids and surfactants as chemical penetration enhancers. [4][5][6] However, these enhancers are only useful for small molecules, 6,7) and it is difficult to achieve meaningful permeation of large peptides. Most recent research has focused on the use of electrical energy to increase drug flux across the skin, including techniques such as iontophoresis, sonophoresis, electroporation, etc. [8][9][10] Unfortunately, the large, complex, and relatively uncharged insulin molecule still cannot across the intercellular lipid layer of the SC. The transport rate of hexameric insulin by iontophoresis across mouse skin has been low and variable.11) Monomeric insulin analogues carrying two additional negative charges have demonstrated transport rates 50-100-fold higher than those of hexameric insulin. However, the quantity of delivery is still not sufficiently high to provide an effective basal insulin level (1 IU/h). 11)To overcome the barrier presented by the SC, proteolytic enzymes maybe used as skin penetration enhancers because their action is highly specific toward proteins and their molecular size is too large to permeate the viable epidermis. Such enzymes perhaps alter skin permeability by provoking biochemical and metabolic events within skin. For more than 50 years, proteolytic enzymes such as trypsin have been extensively used in laboratory settings for in vitro epidermal separation and keratinocyte isolation.12-15) The unique ability of proteases to cause selective epidermal separation has been in part explained by the proteolytic degradation of desmosomal proteins in the SC, which leads to cell dissociation. 16,17) Recently, several endogenous proteases occurring in the epidermis have been found to play important roles in regulating epidermal cell desquamation.18-21) Based on these findings, several therapeutic applications have been attempted for wound debridement and epidermal ablation. [22][23][24] However, no studies have examined the use of such proteolytic enzymes as a penetration enhancers for t...

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supporting

confidence: 84%

Transdermal Delivery of Insulin Using Trypsin as a Biochemical Enhancer

Quan

Zang

et al. 2008

Biological & Pharmaceutical Bulletin

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“…Transdermal delivery has been at the forefront of research addressing the development of non-invasive methods for the systemic administration of peptide and protein therapeutics generated by the biotechnology revolution [16, 39, 84]. Various approaches showed potential to cross the skin’s formidable barrier function.…”

Section: Iontophoretic Research and Drug Deliverymentioning

confidence: 99%

Iontophoresis: A Potential Emergence of a Transdermal Drug Delivery System

Dhote¹

2012

Sci. Pharm.

129

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The delivery of drugs into systemic circulation via skin has generated much attention during the last decade. Transdermal therapeutic systems propound controlled release of active ingredients through the skin and into the systemic circulation in a predictive manner. Drugs administered through these systems escape first-pass metabolism and maintain a steady state scenario similar to a continuous intravenous infusion for up to several days. However, the excellent impervious nature of the skin offers the greatest challenge for successful delivery of drug molecules by utilizing the concepts of iontophoresis. The present review deals with the principles and the recent innovations in the field of iontophoretic drug delivery system together with factors affecting the system. This delivery system utilizes electric current as a driving force for permeation of ionic and non-ionic medications. The rationale behind using this technique is to reversibly alter the barrier properties of skin, which could possibly improve the penetration of drugs such as proteins, peptides and other macromolecules to increase the systemic delivery of high molecular weight compounds with controlled input kinetics and minimum inter-subject variability. Although iontophoresis seems to be an ideal candidate to overcome the limitations associated with the delivery of ionic drugs, further extrapolation of this technique is imperative for translational utility and mass human application.

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“…For macromolecules and protein and peptide structures there have also been a number of encouraging published studies including: calcitonin (salmon) [29], corticotrophin-releasing hormone [30], delta sleep-inducing peptide [31], dextran sulphate [32], inulin [33], insulin [34][35][36][37][38], gonadotropinreleasing hormone [39], growth hormone-releasing factor [40], leuprolide acetate [23,41,43], leutenising hormonereleasing hormone [44][45][46], neutral thyrotrophin-releasing hormone [47], oligonucleotides [48,49], parathyroid hormone [50,51] and vasopressin [52,53]. To date, however, clinical studies have been limited to smaller molecules such as lidocaine [54][55][56], dexamethasone [57], etofenamate [58], naproxen [59], metoclopramide plus hydrocortisone [60], cortisone [61], vincristine [62] and fentanyl [63].…”

Section: Iontophoresismentioning

confidence: 99%

Physical Enhancement of Transdermal Drug Application: Is Delivery Technology Keeping up with Pharmaceutical Development?

Cross

Roberts

2004

CDD

132

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Advances in molecular biology have given us a wide range of protein and peptide-based drugs that are unsuitable for oral delivery because of their high degree of first-pass metabolism. Though parenteral delivery is the obvious answer, for the successful development of commercial chronic and self-administration usage formulations it is not the ideal choice. Transdermal delivery is emerging as the biggest application target for these agents, however, the skin is extremely efficient at keeping out such large molecular weight compounds and therapeutic levels are never going to be realistically achieved by passive absorption. Physical enhancement mechanisms including: iontophoresis, electroporation, ultrasound, photomechanical waves, microneedles and jet-propelled particles are emerging as solutions to this topical delivery dilemma. Adding proteins and peptides to the list of other large molecular weight drugs with insufficient passive transdermal fluxes to be therapeutically useful, we have a collection of pharmacological agents waiting for efficient delivery methods to be introduced. This article reviews the current state of physical transdermal delivery technology, assesses the pros and cons of each technique and summarises the evidence-base of their drug delivery capabilities.

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Transdermal iontophoresis of insulin

Cited by 45 publications

References 25 publications

Transdermal Delivery of Insulin Using Trypsin as a Biochemical Enhancer

Transdermal Delivery of Insulin Using Trypsin as a Biochemical Enhancer

Iontophoresis: A Potential Emergence of a Transdermal Drug Delivery System

Physical Enhancement of Transdermal Drug Application: Is Delivery Technology Keeping up with Pharmaceutical Development?

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