Sustained release of insulin through skin by intradermal microdelivery system

Abstract

An intradermal microdelivery system comprising a wafer having 150-mum long microneedles and an applicator was used for controlled release of insulin. Insulin was topically applied on microneedle-pretreated skin. In vitro percutaneous studies showed that the penetration amount of FITC-Insulin following microneedle pretreatment was enhanced significantly and continued to increase for several hours after the removal of donor phase. In vivo studies on diabetic rats confirmed that the pharmacodynamic profile of percutaneously administrated regular insulin was smooth, with the duration of action comparable to that of subcutaneously injected biphasic insulin. The effects of insulin concentration, duration and area of microneedle treatment on blood glucose lowering were studied in vivo. The results indicated that the duration of microneedle treatment and insulin concentration were key influencing factors to optimize blood glucose control. The extent of blood glucose lowering was in proportion to the area of microneedle treatment.

Application of Microneedle Arrays for Enhancement of Transdermal Permeation of Insulin: In Vitro Experiments, Scaling Analyses and Numerical Simulations

“…4a and which may be due to the resistance shown by the skin for MN insertion as a result of its viscoelastic nature (8,16). In concurrence with the reports published earlier that a large amount of insulin penetrates through the skin after the application of high concentrations of insulin at the donor site, the passive diffusion experiments we conducted resulted in a 1.5-fold increase in the cumulative amount of insulin permeated by increasing insulin strength from 40 to 100 IU and volume from 0.5 to 1 mL as donor vehicle (p<0.05) (11,12). This increase in the insulin permeation may be attributed to increased chemical potential of insulin in donor compartment.…”

“…Some of the works utilized various permeation enhancers alone and along with iontophoresis for insulin permeation enhancement (6,7). Some works were also carried out using microneedles (MN) to enhance the transdermal delivery of insulin (8)(9)(10)(11)(12). While these works show the potential of using MN for enhancement of insulin delivery, and no works depicting a systematic approach to evaluate the overall dependence of insulin permeation on various parameters, for example the MN lengths (MN density in a patch) and insulin donor concentration, etc.…”

Rapid Pharmacokinetics of Intradermal Insulin Administered Using Microneedles in Type 1 Diabetes Subjects

“…[13][14][15][16] Microneedles may reduce this pain, fear, and apprehension because their small size not only causes less physical pain, but also appears less threatening than a hypodermic needle or catheter. [17][18][19][20] In this report, we present the first peer-reviewed study in human subjects to test the hypothesis that intradermal insulin infusion using microneedles leads to more rapid PK, improved postprandial glycemic control, and less pain than subcutaneous catheter-based infusion in subjects with type 1 diabetes.…”

Transdermal Delivery of biopharmaceuticals: Dream or reality?

“…For example, insulin has been used as a model drug for several years in transdermal research. Insulin therapy is used to treat diabetes mellitus and is administered by hypodermic injection [3]. Patient aversion to needles has made the research on noninvasive therapies very relevant.…”

“…Recent focus has shifted from making metal-based microneedles to developing microneedles made of bio- [11] Parathyroid hormone (1-34) 4 Coated microneedles [12], [13] Insulin 6 Hollow microneedles [3,[14][15][16][17] Dissolvable microneedles Solid microneedles Lysozyme 14.3 Dissolvable (polymer) microneedles [18] Human growth hormone 22 Hollow microneedles [19][20][21] Dissolvable (polymer) microneedles Bovine serum albumin 66 Dissolvable (polymer) microneedles [22] Human immunoglobulin 1500 Dissolvable (sugar) microneedles [23] Solid (metal-based) microneedles [18]. Simple modifications of drug loading and patch design allowed these microneedles to deliver a bolus dose or controlled release of the drug.…”