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Title: Enhanced Solubility, Permeability and Anticancer Activity of Vorinostat Using Tailored Mesoporous Silica Nanoparticles.
Austin Authors: Meka, Anand Kumar;Jenkins, Laura J;Dàvalos-Salas, Mercedes;Pujara, Naisarg;Wong, Kuan Yau;Kumeria, Tushar;Mariadason, John M ;Popat, Amirali
Affiliation: Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
School of Pharmacy, The University of Queensland, Brisbane, QLD 4102, Australia
School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia
Mater Research Institute-The University of Queensland, Translational Research Institute, Woolloongabba, QLD 4102, Australia
Issue Date: 17-Dec-2018 2018-12-17
Publication information: Pharmaceutics 2018; 10(4): E283
Abstract: Suberoylanilide 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.
DOI: 10.3390/pharmaceutics10040283
ORCID: 0000-0003-0692-5904
PubMed URL: 30562958
ISSN: 1999-4923
Type: Journal Article
Subjects: BCS classification
drug delivery
particle cell interaction
porous materials
porous silica
Appears in Collections:Journal articles

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