Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10613394 | Journal of Controlled Release | 2005 | 15 Pages |
Abstract
Drugs are optimally effective in the therapeutic concentration range. A challenge in the delivery area is to design a system that will allow the therapeutic range to be accessed and to be maintained for defined periods. The lipidic cubic phases have been used as delivery matrices with such properties. For water-soluble drugs, release from the cubic phase is controlled by transport through aqueous channels that permeate the phase. Channel size can be tuned over wide limits by adjusting temperature and lipid identity. Thus, the possibility exists to regulate the rate of drug release from the cubic phase. With a view to exploiting these features for small molecule, proteinaceous and nucleic acid drugs, we have taken a systematic approach toward understanding how cubic phase transport is controlled by phase identity and microstructure and by the physical and chemical properties of the drug itself. Measurements were made using tryptophan, rubipy, DNA and six proteins as drug surrogates and with three hosting lipids. Remarkably, transport was observed with apo-ferritin whose size far exceeds that of the aqueous channel suggesting a molecular breathing or peristalsis type of facilitated release. Exquisite control over release was achieved by adjusting electrostatic interaction strength and by His-tag displacement.
Related Topics
Physical Sciences and Engineering
Materials Science
Biomaterials
Authors
J. Clogston, M. Caffrey,