Microneedles coated with porous calcium phosphate ceramics: Effective vehicles for transdermal delivery of solid trehalose

Abstract

Trehalose (alpha-D-glucopyranosyl-alpha-D-glucopyranoside) is recognized as a promising fast-dissolving solid reservoir capable of stabilizing the native structure of proteins and suitable for loading with a wide variety of bioactive substances. Currently, there is a growing interest in developing cost-effective methods for immobilizing solid trehalose on arrays of microneedles for delivering protein-based and DNA-based vaccine to the epidermis. In the present work, micro-porous calcium phosphate coatings were used to provide a biocompatible interface with a large surface area for the effective immobilization of trehalose on microneedles. Calcium phosphate coatings with varying degrees of porosity were electrochemically synthesized on the tips of stainless steel acupuncture needles and loaded with solid trehalose. Skin experiments were designed to determine the ability of micro-porous calcium phosphate coatings to deliver solid trehalose into epidermis without breaking during insertion. The mechanical performance of the coatings was assessed by inserting the tips of the coated needles into human skin to an average depth of 100-300 microm and then removing them for analysis by scanning electron microscopy. Microporous calcium phosphate coatings loaded with trehalose effectively breached the stratum corneum and allowed direct access to the epidermis without breaking and without stimulating nerves in deeper tissues.