Dataset Information

Dual-drug nanomedicine with hydrophilic F127-modified magnetic nanocarriers assembled in amphiphilic gelatin for enhanced penetration and drug delivery in deep tumor tissue.

ABSTRACT:

Introduction

Deep penetration of large-sized drug nanocarriers into tumors is important to improve the efficacy of tumor therapy.

Methods

In this study, we developed a size-changeable "Trojan Horse" nanocarrier (THNC) composed of paclitaxel (PTX)-loaded Greek soldiers (GSs; ~20 nm) assembled in an amphiphilic gelatin matrix with hydrophilic losartan (LST) added.

Results

With amphiphilic gelatin matrix cleavage by matrix metalloproteinase-2, LST showed fast release of up to 60% accumulated drug at 6 h, but a slow release kinetic (~20%) was detected in the PTX from the GSs, indicating that THNCs enable controllable release of LST and PTX drugs for penetration into the tumor tissue. The in vitro cell viability in a 3D tumor spheroid model indicated that the PTX-loaded GSs liberated from THNCs showed deeper penetration as well as higher cytotoxicity, reducing a tumor spheroid to half its original size and collapsing the structure of the tumor microenvironment.

Conclusion

The results demonstrate that the THNCs with controlled drug release and deep penetration of magnetic GSs show great potential for cancer therapy.

SUBMITTER: Lai YH

PROVIDER: S-EPMC5968781 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dual-drug nanomedicine with hydrophilic F127-modified magnetic nanocarriers assembled in amphiphilic gelatin for enhanced penetration and drug delivery in deep tumor tissue.

Lai Yen-Ho YH Chiang Chih-Sheng CS Kao Tzu-Hsun TH Chen San-Yuan SY

International journal of nanomedicine 20180522

<h4>Introduction</h4>Deep penetration of large-sized drug nanocarriers into tumors is important to improve the efficacy of tumor therapy.<h4>Methods</h4>In this study, we developed a size-changeable "Trojan Horse" nanocarrier (THNC) composed of paclitaxel (PTX)-loaded Greek soldiers (GSs; ~20 nm) assembled in an amphiphilic gelatin matrix with hydrophilic losartan (LST) added.<h4>Results</h4>With amphiphilic gelatin matrix cleavage by matrix metalloproteinase-2, LST showed fast release of up to ...[more]

PMID: 29861633

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Project description:Self-nanoemulsifying systems (SNEs) have excellent ability to improve the solubility of poorly water-soluble drugs (PWSD). However, SNEs are likely to be degraded in gastrointestinal (GIT) when their surface is recognized by lipase/co-lipase enzyme complex, resulting in rapid release and precipitation of encapsulated drugs. The precipitates are then captured and removed by intestinal mucus, reducing the delivery efficacy of SNEs. Herein, the amphiphilic polymer Pluronic® F127 was incorporated into long and short-chain triglycerides (LCT, SCT) based SNEs to diminish the recognition and therefore minimized their degradation by enzymes and clearance by mucus. The SNEs were characterized in terms of particle size, zeta potential and stability. Ex vivo multiple particles tracking studies were performed by adding particle solution into fresh rat mucus. Cellular uptake of SNEs were conducted by using E12 cells, the absorption and distribution in small intestine were also studied after oral administration in male Sprague-Dawley (SD) rats. The in vitro digestion rate of SNEs were found to be in following order SCT-SNE > SCT-F127-SNE > LCT-SNE > LCT-F127-SNE. Moreover, the LCT-F127-SNE was found to be most effective in enhancing cellular uptake, resulting in 3.5-fold, 2.1-fold and 1.7-fold higher than that of SCT-SNE, LCT-SNE and SCT-F127-SNE, respectively. After incubating the SNE with E12 cells, the LCT-F127-SNE exhibited the highest amount regarding both mucus penetration and cellular uptake, with an uptake amount number (via bicinchoninic acid (BCA) analysis) of 3.5-fold, 2.1-fold and 1.7-fold higher than that of SCT-SNE, LCT-SNE and SCT-F127-SNE, respectively. The in vivo results revealed that orally administered LCT-F127-SNE could significantly increase the bioavailability of Cyclosporine A (CsA), which was approximately 2.43-fold, 1.33-fold and 1.80-fold higher than that of SCT-SNE, SCT-F127-SNE and LCT-SNE, respectively. We address in this work that F127-modified SNEs have potentials to improve oral drug absorption by significantly reducing gastrointestinal enzymatic degradation and simultaneously enhancing mucus penetration.

Dataset Information

Dual-drug nanomedicine with hydrophilic F127-modified magnetic nanocarriers assembled in amphiphilic gelatin for enhanced penetration and drug delivery in deep tumor tissue.

Introduction

Methods

Results

Conclusion

Publications

Dual-drug nanomedicine with hydrophilic F127-modified magnetic nanocarriers assembled in amphiphilic gelatin for enhanced penetration and drug delivery in deep tumor tissue.

Similar Datasets

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