Biophysical Methods of Drug Delivery
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Many medical therapies would benefit from better control over drug transport into and within the body. Medicinal chemists often control drug transport by changing drug structure in ways that alter its physicochemical properties. Pharmacists frequently control drug transport by modifying the drug formulation by encapsulating drugs within carriers or adding excipients. These conventional approaches accept the transport barriers imposed by the body as a given and work to design drugs and formulations that work around those constraints. In our laboratory, we seek to remove those constraints by transiently breaking down transport barriers in the body using biophysical mechanisms. The optimal extent and duration of barrier disruption depends on the nature of the barrier and the desired application. The challenge of this approach is to achieve a balance between perturbing the barrier enough to achieve drug delivery goals, but not so much as to cause lasting damage, safety concerns or pain. In some scenarios, we create micrometer-scale pathways in tissue to target delivery to precise locations within tissues. Using microfabrication technology, we have designed solid microneedle patches with coated or encapsulated drugs and vaccines for painless administration to the skin. We showed that targeted influenza vaccination to the skin in this way induces more potent immune responses compared to conventional intramuscular injection in mice. In addition, hollow microneedles that inject insulin in the skin of human diabetics show faster pharmacokinetics and better blood glucose control compared subcutaneous infusion. We have also shown that hollow microneedles enable injection into the suprachoroidal space of the eye, facilitating minimally invasive drug delivery targeted to the retina in rabbits and pigs. In separate projects, we have used thermal ablation and microdermabrasion to selectively remove the outer permeability barrier of the skin "the stratum corneum" and thereby allow absorption of macromolecules. In other scenarios, we create nanometer-scale holes in cell membranes to drive molecules into tissues and cells more effectively. One approach involves electroporation, which we employ to drive genetic material into cells for gene therapy and DNA vaccination and to increase permeability of epithelial barriers to increase drug absorption. We also study the use of ultrasound under conditions that generate cavitational bubble activity, which can be harnessed to increase cell membrane permeability for uptake of macromolecules. More recently, we have employed laser-activated nanoparticles that similarly open cell membranes for drug uptake by a mechanism believed to involve cavitation as well. Overall, we seek to enable and increase the efficacy of pharmaceutical therapies by transiently disrupting transport barriers in the body at the nanometer and micrometer lengthscales in order to increase uptake and target delivery of drugs, proteins, DNA and vaccines.
- NanoFANS Forum