Discovery of transdermal penetration enhancers by high-throughput screening

Although transdermal drug delivery is more attractive than injection, it has not been applied to macromolecules because of low skin permeability. Here we describe particular mixtures of penetration enhancers that increase skin permeability to macromolecules (∼1–10 kDa) by up to ∼100-fold without ind...

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Bibliographic Details
Published in:Nature biotechnology 2004-02, Vol.22 (2), p.192-197
Main Authors: Mitragotri, Samir, Karande, Pankaj, Jain, Amit
Format: Article
Language:English
Subjects:
Administration, Cutaneous
Agriculture
Animals
Bioinformatics
Biological and medical sciences
Biomedical and Life Sciences
Biomedical Engineering/Biotechnology
Biomedicine
Biotechnology
Drug Delivery Systems - methods
Drug Evaluation - methods
Drug Synergism
Feasibility Studies
Fundamental and applied biological sciences. Psychology
Health. Pharmaceutical industry
high-throughput screening
Humans
Impedance
Industrial applications and implications. Economical aspects
Injection
Life Sciences
Miscellaneous
Permeability
Pharmaceutical Preparations - administration & dosage
Pharmaceutical Vehicles - administration & dosage
Pharmaceutical Vehicles - pharmacokinetics
Rats
Skin - drug effects
Skin - metabolism
Skin Absorption - drug effects
Skin Absorption - physiology
Sodium
Sulfates
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Summary:Although transdermal drug delivery is more attractive than injection, it has not been applied to macromolecules because of low skin permeability. Here we describe particular mixtures of penetration enhancers that increase skin permeability to macromolecules (∼1–10 kDa) by up to ∼100-fold without inducing skin irritation. The discovery of these mixtures was enabled by an experimental tool, in vitro skin impedance guided high-throughput (INSIGHT) screening, which is >100-fold more efficient than current tools. In vitro experiments demonstrated that the mixtures delivered macromolecular drugs, including heparin, leutinizing hormone releasing hormone (LHRH) and oligonulceotides, across the skin. In vivo experiments on hairless rats with leuprolide acetate confirmed the potency and safety of one such mixture, sodium laureth sulfate (SLA) and phenyl piperazine (PP). These studies show the feasibility of using penetration enhancers for systemic delivery of macromolecules from a transdermal patch.
ISSN:1087-0156
1546-1696
DOI:10.1038/nbt928