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J Control Release. 2014 Sep 28;190:157-71. doi: 10.1016/j.jconrel.2014.04.049. Epub 2014 May 4.

Single compartment drug delivery.

Author information

1
The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Materials Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: mjcima@mit.edu.
2
TARIS Biomedical, Inc., Lexington, MA 02421, USA.
3
The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
4
The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Materials Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
5
The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
6
On Demand Therapeutics, Inc., Menlo Park, CA 94025, USA.
7
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Abstract

Drug design is built on the concept that key molecular targets of disease are isolated in the diseased tissue. Systemic drug administration would be sufficient for targeting in such a case. It is, however, common for enzymes or receptors that are integral to disease to be structurally similar or identical to those that play important biological roles in normal tissues of the body. Additionally, systemic administration may not lead to local drug concentrations high enough to yield disease modification because of rapid systemic metabolism or lack of sufficient partitioning into the diseased tissue compartment. This review focuses on drug delivery methods that physically target drugs to individual compartments of the body. Compartments such as the bladder, peritoneum, brain, eye and skin are often sites of disease and can sometimes be viewed as "privileged," since they intrinsically hinder partitioning of systemically administered agents. These compartments have become the focus of a wide array of procedures and devices for direct administration of drugs. We discuss the rationale behind single compartment drug delivery for each of these compartments, and give an overview of examples at different development stages, from the lab bench to phase III clinical trials to clinical practice. We approach single compartment drug delivery from both a translational and a technological perspective.

KEYWORDS:

Controlled release drug delivery; Local therapy; Microfabrication; Noninvasive; Single compartment; Targeted therapy

PMID:
24798478
PMCID:
PMC4179298
DOI:
10.1016/j.jconrel.2014.04.049
[Indexed for MEDLINE]
Free PMC Article

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