Using micro-nanostructures to deliver genes and drugs to skin for immunotherapeutic applications

A problem presented at the UK MMSG Oxford 2005.

Presented by:
Dr Mark Kendall (The PowderJect Centre for Gene and Drug Delivery Research, University of Oxford)

Problem Description

The provision of safe and efficient routes of delivery of polynucleotides to the immunologically sensitive Langerhans cells in the skin (and mucosa) has the potential to enhance DNA vaccine strategies in the treatment of major disease. The application of practical, commercially-viable physical methods to the achievement of this goal presents unique engineering challenges in the physical transport of polynucleotides to the nuclei of these cells.

We are developing two physical targeting methods, one using micro-particles and the other using nanostructures. The first, called Biolistics (or Gene Guns), operates by accelerating micro-particles coated in DNA to a momentum sufficient to ballistically penetrate the human skin to achieve an immunological effect. The microparticles are transported to the tissue by a high-speed helium gas flow generated within a hand-held nozzle based delivery system. The effectiveness of ballistic microparticle to the skin is often dependant on breaching the SC and targeting cells within defined layers of the viable epidermis. With a typical impact velocity of 600 m/s, the micro-particles come to rest in the epidermis within 100 ns. Under this highly dynamic loading, key material properties of the skin are very different to typical quasi-static conditions exhibited by a range of more common interactions (e.g. touch). Furthermore, microscopy imaging experiments show the action of particle impact leads to considerable cell death. The second-in an earlier research stage-employs an array of thousands of micro-nanoprojections administered on a patch to deliver genes and drugs to epidermal cells. This approach has many advantages over the biolistics that will be discussed, along with initial calculations and data outlining the device design and its utility.

Study Group Report

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