Study Of Preparation Technology For Insulin Microneedles

All patients with type 1 diabetes and some with type 2 diabetes need to give exogenous insulin to control blood sugar and prevent complications.However,lifetime frequent injections,inconvenient storage(such as refrigeration and anti-frozen),as well as the risk of overdose and hypoglycemia greatly compromise the patient’s life quality.Non-and minimal invasive administration of insulin have therefore been highly demanded for nearly a century.Compared with the inefficiency of oral dose and inaccuracy of inhalation,the recently reported microneedle-based transdermal delivery shows to be more promising for non-injecting administration of insulin.Unlike other skin permeability enhancement such as chemical enhancers,electric field,and ultrasound,microneedles penetrate the epidermis,the primary permeability barrier of the skin,by minimal invasion.The expected transdermal efficiency has already attracted intensive research efforts to microneedle-based transdermal drug delivery.Phase-transition microneedles(PTM)patch invented by the laboratory where the present study was carried out represents a new generation of microneedle systems that overcomes the limitations of existing solid microneedles,hollow microneedles and dissolvable microneedles.The needle tips of PMT are formed of polyvinyl alcohol(PVA),a chemically inert pharmaceutical excipient that forms sub-microcrystalline domains as cross-linking junctions by freeze-thaw treatment post molding.The needle tips of PTM are sufficiently strong to penetrate the epidermis at dry state and to withdraw from the skin at swollen state,a nature preventing polymer deposition in the skin and allowing termination of medication whenever hypoglycemia is a concern.PTM also differs from other swellable but insoluble microneedles;its microcrystalline cross-linking process is mild and friendly to delicate proteins so that the medicines can be loaded in the needle tips for efficient transdermal release.The drawback of PTM may be that its onset response is approximately 20-30 min slower than the injections of quick-acting insulin.The primary objective of the present study is to accelerate insulin release from PTM by optimizing the microneedle formulation and fabrication process.The experimental details are outlined below.1.Performance study of PTFE microneedle moldMold is one of the key factors for the formation of phase-transition microneedles.Molds with different parameters are investigated by the amount of solution loaded and the easiness of peeling the microneedle patches off the molds.2.Preparation of fast-acting insulin microneedlesIn order to achieve more rapid release of insulin from microneedles,impregnation method is introduced.Insulin is loaded by impregnating microneedles in insulin solution.Impregnation devices and methods are designed and investigated.In-vitro release data show fast release of insulin loaded into microneedles by impregnation.3.Feasibility evaluation by in vivo experimentInsulin microneedles prepared by impregnation and premixing methods are investigated by applying them on diabetic rats.Data shows that both kinds of insulin microneedles are effective and insulin microneedles made by impregnation lower blood sugar faster than those made by premixing with same dosage,proving the feasibility of making fast-acting insulin microneedles by impregnation method.