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Nanoparticle delivery of an AKT/PDK1 inhibitor improves the therapeutic effect in pancreatic cancer

Lucero-Acuña, Armando ; Jeffery, Justin J ; Abril, Edward R ; Nagle, Raymond B ; Guzman, Roberto ; Pagel, Mark D ; Meuillet, Emmanuelle J

International journal of nanomedicine, 2014-01, Vol.9 (Issue 1), p.5653-5665 [Periódico revisado por pares]

New Zealand: Dove Medical Press Limited

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Título:
Nanoparticle delivery of an AKT/PDK1 inhibitor improves the therapeutic effect in pancreatic cancer
Autor: Lucero-Acuña, Armando ; Jeffery, Justin J ; Abril, Edward R ; Nagle, Raymond B ; Guzman, Roberto ; Pagel, Mark D ; Meuillet, Emmanuelle J
Assuntos: Acids ; AKT ; Alcohol ; Animals ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacokinetics ; Antineoplastic Agents - pharmacology ; bioluminescence imaging ; Cancer therapies ; Cell Line, Tumor ; Drug Carriers - chemistry ; drug delivery ; Drug delivery systems ; Drug therapy ; Drugs ; Extracellular matrix ; Female ; Genetic aspects ; Health aspects ; Humans ; Lactic Acid - chemistry ; Medical research ; Mice ; Mice, SCID ; Molecular weight ; Mutation ; Nanoparticles ; Nanoparticles - chemistry ; Optical Imaging ; Original Research ; Pancreatic cancer ; Pancreatic Neoplasms - metabolism ; Physiological aspects ; Polyglycolic Acid - chemistry ; Protein Kinase Inhibitors - chemistry ; Protein Kinase Inhibitors - pharmacokinetics ; Protein Kinase Inhibitors - pharmacology ; Proto-Oncogene Proteins c-akt - antagonists & inhibitors ; Proto-Oncogene Proteins c-akt - metabolism ; Studies ; Tumors ; Vehicles
É parte de: International journal of nanomedicine, 2014-01, Vol.9 (Issue 1), p.5653-5665
Descrição: The K-ras mutation in pancreatic cancer can inhibit drug delivery and increase drug resistance. This is exemplified by the therapeutic effect of PH-427, a small molecule inhibitor of AKT/PDK1, which has shown a good therapeutic effect against a BxPC3 pancreatic cancer model that has K-ras, but has a poor therapeutic effect against a MiaPaCa-2 pancreatic cancer model with mutant K-ras. To increase the therapeutic effect of PH-427 against the MiaPaCa-2 pancreatic cancer model with mutant K-ras, we encapsulated PH-427 into poly(lactic-co-glycolic acid) nanoparticles (PNP) to form drug-loaded PH-427-PNP. PH-427 showed a biphasic release from PH-427-PNP over 30 days during studies in sodium phosphate buffer, and in vitro studies revealed that the PNP was rapidly internalized into MiaPaCa-2 tumor cells, suggesting that PNP can improve PH-427 delivery into cells harboring mutant K-ras. In vivo studies of an orthotopic MiaPaCa-2 pancreatic cancer model showed reduced tumor load with PH-427-PNP as compared with treatment using PH-427 alone or with no treatment. Ex vivo studies confirmed the in vivo results, suggesting that PNP can improve drug delivery to pancreatic cancer harboring mutant K-ras.
Editor: New Zealand: Dove Medical Press Limited
Idioma: Inglês

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Nanoparticle delivery of an AKT/PDK1 inhibitor improves the therapeutic effect in pancreatic cancer

Lucero-Acuña, Armando ; Jeffery, Justin J ; Abril, Edward R ; Nagle, Raymond B ; Guzman, Roberto ; Pagel, Mark D ; Meuillet, Emmanuelle J

New Zealand: Dove Medical Press Limited

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