Polymeric Microneedle Device for Transcutaneous Delivery of Antigen and Chemotherapeutics

Abstract

Microneedles have been used to deliver a wide variety of different low molecular weight drugs, biotherapeutics and vaccines, including reports of clinical trials with newlinea number of small molecules, biomacromolecules and vaccines. Microneedles have also been employed for delivery of actives into the eye and into cells. The newlineaim of the current thesis work was to understand the deliverability of different newlinedrug molecules from polymeric microneedles. Corn protein zein, and synthetic polymers polyvinyl alchohol and polyvinyl pyrrolidone were used to fabricate microneedles in two different designs and geometries. Zein microneedles were investigated for their potential for transcutaneous immunization. Conical microneedles with a height of 974.6 ± 13.8 and#956;m and a base diameter of 362.7 ± 13.8 and#956;m with a smooth surface were formed using the micromolding technique. The insertion of zein microneedles and the delivery of the model antigen, ovalbumin into the skin was confirmed by histological examination and confocal microscopy. Using fluorescence labelled S. epidermidis,a significantly lower permeation of bacteria was seen with microneedle treatment against hypodermal syringe application. Stability of ovalbumin coated on zein microneedles was investigated using SDS-PAGE and circular dichroism. Stability evaluation of ovalbumin coated zein microneedles suggested 2 month stability of newlinethe preparation under ambient and cold conditions. Transcutaneous immunization newlinestudies in Balb/c mice showed significantly (p lt 0.001) greater antibody titers newline(total anti-OVA IgG, IgG1, and IgG2a) after the application of ovalbumin coated zein microneedles and intradermal injection of ovalbumin compared with the control group. Splenocyte proliferation further suggested that ovalbumin coated zein microneedles have the ability to enhance the antigen presentation to the Tcells and to induce a long-lasting immune response. Zein microneedles were further studied for delivery of two chemotherapeutic agents with contrasting physicochemical characteristics, tam