Lipid-coated microgels for the triggered release of doxorubicin.
We have systematically engineered a polymeric, multi-component drug delivery system composed of a lipid-coated hydrogel microparticle (microgel). The design of this delivery system was motivated by the recent elucidation of the mechanism of regulated secretion from the secretory granule and the compositional and structural features that underlie its ability to store and release endogenous drug-like compounds. The present work describes the assembly and response of a prototype construct which displays several important features of the secretory granule, including its high drug loading capacity, and triggered microgel swelling, resulting in the burst release of drug. To achieve this, ionic microgels were synthesized, and loaded with doxorubicin via ion exchange. These microgels were then coated with a lipid bilayer, and the release of doxorubicin was triggered from the gels using either lipid-solubilizing surfactants or electroporation. The use of a microanalytical technique is featured utilizing micropipette manipulation that allows the study of the behavior of individual microparticles. The lipid-coated microgels were electroporated in saline solution; they swelled and disrupted their bilayer coating over a period of several seconds and exchanged doxorubicin with the external plasma saline over a period of several minutes. It is envisioned that this system will ultimately find utility in drug delivery systems that are designed to release chemotherapeutic agents and peptides by the application of a triggering signal.
Kiser
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PF
The Glynn Wilson Group, 700 NW Gilman Blvd E103, 98027-5335, Issaquah, WA 98027-5335, USA.
Wilson
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Needham
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D000970:Antineoplastic Agents / Q000008:administration & dosage*; D003594:Cytoplasmic Granules; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods*; D020100:Hydrogels / Q000008:administration & dosage*; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000008:administration & dosage
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D020100:Hydrogels; D008051:Lipid Bilayers; D004317:Doxorubicin