Development of lipid nanoparticles for a histone deacetylases inhibitor as a promising anticancer therapeutic

Tran, Tuan Hiep; Chu, Duc Thanh; Truong, Duy Hieu; Tak, Jin Wook; Jeong, Jee–Heon; Hoang, Van Luong; Yong, Chul Soon; Kim, Jong Oh

doi:10.3109/10717544.2014.991432

Cited by 22 publications

(10 citation statements)

References 38 publications

(41 reference statements)

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“…As VRS and DTX are both hydrophobic drugs, they can be carried on a lipophilic, biocompatible vehicle with a high loading capacity to amplify their activity [4,38,39] . In the past few decades, lipid carriers have proven an attractive option through the incorporation of hydrophobic agents into the lip ophilic matrix as an effective delivery system into the body [40,41] .…”

Section: Resultsmentioning

confidence: 99%

Synergistic Therapeutic Strategy of Dual Drug-loaded Lipid Polymer Hybrid Nanoparticles for Breast Cancer Treatment

Tran¹,

Nguyen²,

Chen³

et al. 2019

pharmaceutical-sciences

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Tran et al.: Dual Drug-loaded Lipid Polymer Hybrid Nanoparticles In this investigation, a smart nanocarrier-loaded docetaxel, a microtubules disrupting agent and vorinostat, a histone deacetylase inhibitor was developed to achieve a synergistic anticancer effect. Dual drug-loaded lipid polymer hybrid nanoparticles were prepared, with easy fabrication and favourable properties including small size, narrow distribution and a high loading effi cacy. The in vitro drug release conducted in phosphatebuffered saline, pH 7.4 and acetate-buffered saline, pH 5.5 media demonstrated the sustained, pH-dependent release profi le. The nanoparticles were effectively taken up by cells, which ensured greater suppression of cell growth. The co-delivery of both drugs exhibited a synergistic effect on the induction of cancer cell apoptosis, resulting in greater inhibition of SCC-7, MCF-7, and MDA-MB-231 cancer cells by the drug-loaded carrier. These promising results may lead to clinical applications with enhanced docetaxel activity.

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Section: Resultsmentioning

confidence: 99%

Synergistic Therapeutic Strategy of Dual Drug-loaded Lipid Polymer Hybrid Nanoparticles for Breast Cancer Treatment

Tran¹,

Nguyen²,

Chen³

et al. 2019

pharmaceutical-sciences

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“…Better strategies to enhance the bioavailability of vorinostat are therefore needed. While previous studies have investigated the use of polymeric and lipidic nanoparticles to deliver vorinostat for tumour therapy [38,47,48,49,50], the majority of these studies focused on the intracellular delivery of vorinostat in cancer cells. Recently, Kim et al, encapsulated vorinostat within solid lipid and liquid lipid, and showed marked improvement in oral bioavailability.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Kim et al, encapsulated vorinostat within solid lipid and liquid lipid, and showed marked improvement in oral bioavailability. However, their formulation suffered from low encapsulation capacity (~2–3% loading), and the effect of encapsulation on solubility, permeability and anti-cancer activity was not studied [38,50].…”

Section: Discussionmentioning

confidence: 99%

“…The approved marketed oral formulation ZOLINZA ® contains 100 mg of vorinostat and has to be taken up to 4 times a day due to poor oral bioavailability. The parenteral formulations of this drug also suffer from poor half-life in the blood (40 mins) after intravenous administration [38]. We hypothesised that use of nanostructured materials such as mesoporous silica as a delivery vehicle may significantly improve the physicochemical properties of BCS class IV molecules such as vorinostat.…”

Section: Introductionmentioning

confidence: 99%

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Enhanced Solubility, Permeability and Anticancer Activity of Vorinostat Using Tailored Mesoporous Silica Nanoparticles

et al. 2018

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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.

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“…An improvement of the anti-tumor effect was observed when the vectored HDACi was combined with chemo–radiotherapy and compared to the free HDACi [15]. When loaded in solid lipid nanoparticles or nanostructured lipid carriers, vorinostat is more cytotoxic on breast cancer and lung cancer cell lines than the free drug [12,16]. Cholesteryl butyrate solid lipid has shown a better activity than the free butyrate on breast and promyelocytic leukemia cancer cell lines [17].…”

Section: Concepts For Delivery Of Epigenetic Modulatorsmentioning

confidence: 99%

The ROMP: A Powerful Approach to Synthesize Novel pH-Sensitive Nanoparticles for Tumor Therapy

2019

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Fast clearance, metabolism, and systemic toxicity are major limits for the clinical use of anti-cancer drugs. Histone deacetylase inhibitors (HDACi) present these defects, despite displaying promising anti-tumor properties on tumor cells in vitro and in in vivo models of cancer. The specific delivery of anti-cancer drugs into the tumor should improve their clinical benefit by limiting systemic toxicity and by increasing the anti-tumor effect. This paper deals with the synthesis of the polymeric nanoparticle platform, which was produced by Ring-Opening Metathesis Polymerization (ROMP), able to release anti-cancer drugs in dispersion, such as histone deacetylase inhibitors, into mesothelioma tumors. The core-shell nanoparticles (NPs) have stealth properties due to their poly(ethylene oxide) shell and can be viewed as universal nano-carriers on which any alkyne-modified anti-cancer molecule can be grafted by click chemistry. A cleavage reaction of the chemical bond between NPs and drugs through the contact of NPs with a medium presenting an acidic pH, which is typically a cancer tumor environment or an acidic intracellular compartment, induces a controlled release of the bioactive molecule in its native form. In our in vivo syngeneic model of mesothelioma, a highly selective accumulation of the particles in the tumor was obtained. The release of the drugs led to an 80% reduction of tumor weight for the best compound without toxicity. Our work demonstrates that the use of theranostic nanovectors leads to an optimized delivery of epigenetic inhibitors in tumors, which improves their anti-tumor properties in vivo.

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Development of lipid nanoparticles for a histone deacetylases inhibitor as a promising anticancer therapeutic

Cited by 22 publications

References 38 publications

Synergistic Therapeutic Strategy of Dual Drug-loaded Lipid Polymer Hybrid Nanoparticles for Breast Cancer Treatment

Synergistic Therapeutic Strategy of Dual Drug-loaded Lipid Polymer Hybrid Nanoparticles for Breast Cancer Treatment

Enhanced Solubility, Permeability and Anticancer Activity of Vorinostat Using Tailored Mesoporous Silica Nanoparticles

The ROMP: A Powerful Approach to Synthesize Novel pH-Sensitive Nanoparticles for Tumor Therapy

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