Bifunctional succinylated ε-polylysine-coated mesoporous silica nanoparticles for pH-responsive and intracellular drug delivery targeting the colon

Nguyen, Chau T. H., Webb, Richard I., Lambert, Lynette K., Strounina, Ekaterina, Lee, Edward C., Parat, Marie-Odile, McGuckin, Michael A., Popat, Amirali, Cabot, Peter J. and Ross, Benjamin P. (2017) Bifunctional succinylated ε-polylysine-coated mesoporous silica nanoparticles for pH-responsive and intracellular drug delivery targeting the colon. ACS Applied Materials and Interfaces, 9 11: 9470-9483. doi:10.1021/acsami.7b00411


Author Nguyen, Chau T. H.
Webb, Richard I.
Lambert, Lynette K.
Strounina, Ekaterina
Lee, Edward C.
Parat, Marie-Odile
McGuckin, Michael A.
Popat, Amirali
Cabot, Peter J.
Ross, Benjamin P.
Title Bifunctional succinylated ε-polylysine-coated mesoporous silica nanoparticles for pH-responsive and intracellular drug delivery targeting the colon
Journal name ACS Applied Materials and Interfaces   Check publisher's open access policy
ISSN 1944-8252
1944-8244
Publication date 2017-03-22
Year available 2017
Sub-type Article (original research)
DOI 10.1021/acsami.7b00411
Open Access Status Not yet assessed
Volume 9
Issue 11
Start page 9470
End page 9483
Total pages 14
Place of publication Washington, DC, United States
Publisher American Chemical Society
Language eng
Subject 2500 Materials Science
Abstract Conventional oral drug formulations for colonic diseases require the administration of high doses of drug to achieve effective drug concentrations at the target site. However, this exposes patients to serious systemic toxicity in order to achieve efficacy. To overcome this problem, an oral drug delivery system was developed by loading a large amount (ca. 34% w/w) of prednisolone into 3-aminopropyl-functionalized mesoporous silica nanoparticles (MCM-NH) and targeting prednisolone release to the colon by coating the nanoparticle with succinylated ε-polylysine (SPL). We demonstrate for the first time the pH-responsive ability of SPL as a “nanogate” to selectively release prednisolone in the pH conditions of the colon (pH 5.5-7.4) but not in the more acidic conditions of the stomach (pH 1.9) or small intestine (pH 5.0). In addition to targeting drug delivery to the colon, we explored whether the nanoparticles could deliver cargo intracellularly to immune cells (RAW 264.7 macrophages) and intestinal epithelial cells (LS 174T and Caco-2 adenocarcinoma cell lines). To trace uptake, MCM-NH were loaded with a cell membrane-impermeable dye, sulforhodamine B. The SPL-coated nanoparticles were able to deliver the dye intracellularly to RAW 264.7 macrophages and the intestinal epithelial cancer cells, which offers a highly promising and novel drug delivery system for diseases of the colon such as inflammatory bowel disease and colorectal cancer.
Formatted abstract
Conventional oral drug formulations for colonic diseases require the administration of high doses of drug to achieve effective drug concentrations at the target site. However, this exposes patients to serious systemic toxicity in order to achieve efficacy. To overcome this problem, an oral drug delivery system was developed by loading a large amount (ca. 34% w/w) of prednisolone into 3-aminopropyl-functionalized mesoporous silica nanoparticles (MCM-NH2) and targeting prednisolone release to the colon by coating the nanoparticle with succinylated ε-polylysine (SPL). We demonstrate for the first time the pH-responsive ability of SPL as a “nanogate” to selectively release prednisolone in the pH conditions of the colon (pH 5.5-7.4) but not in the more acidic conditions of the stomach (pH 1.9) or small intestine (pH 5.0). In addition to targeting drug delivery to the colon, we explored whether the nanoparticles could deliver cargo intracellularly to immune cells (RAW 264.7 macrophages) and intestinal epithelial cells (LS 174T and Caco-2 adenocarcinoma cell lines). To trace uptake, MCM-NH2 were loaded with a cell membrane-impermeable dye, sulforhodamine B. The SPL-coated nanoparticles were able to deliver the dye intracellularly to RAW 264.7 macrophages and the intestinal epithelial cancer cells, which offers a highly promising and novel drug delivery system for diseases of the colon such as inflammatory bowel disease and colorectal cancer.
Keyword Colon targeted drug delivery
Intracellular drug delivery
Mesoporous silica nanoparticles
PH-responsive
Prednisolone
Succinylated ε-polylysine
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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