A unique biomedical delivery system (biolistics), for micro-sized powder formulation of drugs (typically protein- and/or DNA-based macromolecules) to be effectively and efficiently delivered into human skin or mucosal tissue for the treatment of a scope of diseases, has been proposed. One of the key concerns for designing and evaluating the biolistic system is to warrant that inicro-particles are accelerated and penetrated in to the skin with a controllable velocity range and uniform spatial distribution for optimal targeting the cells of interest. In this paper, we numerically interrogate the performance of a prototype biolistic device, designed for a uniform micro-particle acceleration and penetration. Swirling effects on the gas-particle dynamics, the particle acceleration and penetration as well as the device performance are presented and interpreted. Variations of the inicro-particle velocity range and spatial distribution with swirl ratios are examined. The ability of the inicro-particles penetrating in to a model skin target is demonstrated and discussed. (c) 2007 Elsevier B.V. All rights reserved.