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dc.contributor.authorMeka, AK
dc.contributor.authorJenkins, LJ
dc.contributor.authorDavalos-Salas, M
dc.contributor.authorPujara, N
dc.contributor.authorWong, KY
dc.contributor.authorKumeria, T
dc.contributor.authorMariadason, JM
dc.contributor.authorPopat, A
dc.date.accessioned2020-12-10T00:35:22Z
dc.date.available2020-12-10T00:35:22Z
dc.date.issued2018-12-01
dc.identifierpii: pharmaceutics10040283
dc.identifier.citationMeka, A. K., Jenkins, L. J., Davalos-Salas, M., Pujara, N., Wong, K. Y., Kumeria, T., Mariadason, J. M. & Popat, A. (2018). Enhanced Solubility, Permeability and Anticancer Activity of Vorinostat Using Tailored Mesoporous Silica Nanoparticles. PHARMACEUTICS, 10 (4), https://doi.org/10.3390/pharmaceutics10040283.
dc.identifier.issn1999-4923
dc.identifier.urihttp://hdl.handle.net/11343/253521
dc.description.abstractSuberoylanilide hydroxamic acid (SAHA) or vorinostat (VOR) is a potent inhibitor of class I histone deacetylases (HDACs) that is approved for the treatment of cutaneous T-cell lymphoma. However, it has the intrinsic limitations of low water solubility and low permeability which reduces its clinical potential especially when given orally. Packaging of drugs within ordered mesoporous silica nanoparticles (MSNs) is an emerging strategy for increasing drug solubility and permeability of BCS (Biopharmaceutical Classification System) class II and IV drugs. In this study, we encapsulated vorinostat within MSNs modified with different functional groups, and assessed its solubility, permeability and anti-cancer efficacy in vitro. Compared to free drug, the solubility of vorinostat was enhanced 2.6-fold upon encapsulation in pristine MSNs (MCM-41-VOR). Solubility was further enhanced when MSNs were modified with silanes having amino (3.9 fold) or phosphonate (4.3 fold) terminal functional groups. Moreover, permeability of vorinostat into Caco-2 human colon cancer cells was significantly enhanced for MSN-based formulations, particularly MSNs modified with amino functional group (MCM-41-NH₂-VOR) where it was enhanced ~4 fold. Compared to free drug, vorinostat encapsulated within amino-modified MSNs robustly induced histone hyperacetylation and expression of established histone deacetylase inhibitor (HDACi)-target genes, and induced extensive apoptosis in HCT116 colon cancer cells. Similar effects were observed on apoptosis induction in HH cutaneous T-cell lymphoma cells. Thus, encapsulation of the BCS class IV molecule vorinostat within MSNs represents an effective strategy for improving its solubility, permeability and anti-tumour activity.
dc.languageEnglish
dc.publisherMDPI
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleEnhanced Solubility, Permeability and Anticancer Activity of Vorinostat Using Tailored Mesoporous Silica Nanoparticles
dc.typeJournal Article
dc.identifier.doi10.3390/pharmaceutics10040283
melbourne.affiliation.departmentMedicine (Austin & Northern Health)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titlePharmaceutics
melbourne.source.volume10
melbourne.source.issue4
dc.rights.licenseCC BY
melbourne.elementsid1366143
melbourne.contributor.authorMariadason, John
dc.identifier.eissn1999-4923
melbourne.accessrightsOpen Access


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