TY - JOUR
T1 - Lipid-coated microgels for the triggered release of doxorubicin
AU - Kiser, Patrick F.
AU - Wilson, Glynn
AU - Needham, David
N1 - Funding Information:
We thank Drs. J. Fernandez and P. Verdugo for helpful discussions, Dr. P. Marszalek for guidance on microelectroporation, and Dr. John Rice for reviewing the manuscript. We thank Access Pharmaceuticals Inc., Dallas, TX, for support of this work.
PY - 2000/7/31
Y1 - 2000/7/31
N2 - 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. Copyright (C) 2000 Elsevier Science B.V.
AB - 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. Copyright (C) 2000 Elsevier Science B.V.
KW - Anti-neoplastic agents
KW - Drug delivery
KW - Lipid bilayer
KW - Poly(methacrylic acid-co-methylene-bis-acrylamide) hydrogels
KW - Secretory granule
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U2 - 10.1016/S0168-3659(00)00236-4
DO - 10.1016/S0168-3659(00)00236-4
M3 - Article
C2 - 10884575
AN - SCOPUS:0034738836
VL - 68
SP - 9
EP - 22
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 1
ER -