Title:
Biophysical Methods of Drug Delivery
Biophysical Methods of Drug Delivery
Author(s)
Prausnitz, Mark R.
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Abstract
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.
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Date Issued
2010-11-18
Extent
41:02 minutes
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