Browsing by Author "Li, Wei-Ming"

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Amifostine-conjugated pH-sensitive calcium phosphate-covered magnetic-amphiphilic gelatin nanoparticles for controlled intracellular dual drug release for dual-targeting in HER-2-overexpressing breast cancer
(2015-12-28)
Li, Wei-Ming
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Chiang, Chih-Sheng
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Huang, Wei-Chen
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Su, Chia-Wei
;
Chiang, Min-Yu
We developed a surfactant-free method utilizing amifostine to stably link a targeting ligand (Herceptin) to amphiphilic gelatin (AG)-iron oxide@calcium phosphate (CaP) nanoparticles with hydrophobic curcumin (CUR) and hydrophilic doxorubicin (DOX) encapsulated in the AG core and CaP shell (AGIO@CaP-CD), respectively. This multi-functional nanoparticle system has a pH-sensitive CaP shell and degradable amphiphilic gelatin (AG) core, which enables controllable sequential release of the two drugs. The dual-targeting system of AGIO@CaP-CD (HER-AGIO@CaP-CD) with a bioligand and magnetic targeting resulted in significantly elevated cellular uptake in HER2-overexpressing SKBr3 cells and more efficacious therapy than delivery of targeting ligand alone due to the synergistic cell multi-drug resistance/apoptosis-inducing effect of the CUR and DOX combination. This nanoparticle combined with Herceptin and iron oxide nanoparticles not only provided a dual-targeting functionality, but also encapsulated CUR and DOX as a dual-drug delivery system for the combination therapy. This study further demonstrated that the therapeutic efficacy of this dual-targeting co-delivery system can be improved by modifying the application duration of magnetic targeting, which makes this combination therapy system a powerful new tool for in vitro/in vivo cancer therapy, especially for HER2-positive cancers. (C) 2015 Elsevier B.V. All rights reserved.
Amphiphilically-modified gelatin nanoparticles: Self-assembly behavior, controlled biodegradability, and rapid cellular uptake for intracellular drug delivery
(2011)
Li, Wei-Ming
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Liu, Dean-Mo
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Chen, San-Yuan
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材料科學與工程學系
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Department of Materials Science and Engineering
An amphiphilic gelatin macromolecule capable of self-assembling to form micelle-like nanospheres for entrapping hydrophobic therapeutic molecules was successfully synthesized by grafting hydrophobic hexanoyl anhydrides to the amino groups of primitive gelatin. The substitution and grafting efficiency of the modified gelatin displayed a concentration-dependent manner toward the hexanoyl anhydride. The particle size and stability of the resulting self-assembled nanoparticles strongly depend on the degree of substitution of the gelatin. These gelatin nanoparticles exhibited an outstanding cytocompatibility and highly efficient drug encapsulation efficiency. The drug release profile of the anticancer agent (camptothecin) from the amphiphilic gelatin nanoparticles shows that the drug release mechanism is dominated by a combined effect of diffusion and degradation. Furthermore, a tunable sustained release and degradation behavior can be controlled by changing the degree of substitution of the gelatin. This new type of amphiphilic gelatin nanoparticles with controlled biodegradability and rapid cellular internalization may serve in the intracellular delivery of specific proteins or genes, permitting a novel design for intracellularly-based nanotherapy.
In situ DOX-calcium phosphate mineralized CPT-amphiphilic gelatin nanoparticle for intracellular controlled sequential release of multiple drugs
(2015-03-15)
Li, Wei-Ming
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Su, Chia-Wei
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Chen, Yu-Wei
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Chen, San-Yuan
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材料科學與工程學系
A co-delivery strategy has been developed to achieve the synergistic effect of a hydrophobic drug (camptothecin, CPT) and a hydrophilic drug (doxorubicin, DOX) by utilizing the unique structure of amphiphilic gelatin/camptothecin @calcium phosphate-doxorubicin (AG/CPT@CaP-DOX) nanoparticles as a carriers in order to replace double emulsions while preserving the advantages of inorganic materials. The hydrophobic agent (CPT) was encapsulated via emulsion with an amphiphilic gelatin core, and subsequently mineralized by CaP-hydrophilic drug (DOX) through precipitation to form a CaP shell on the CPT-AG amphiphilic gelatin core so that drug molecules with different characteristics (i.e. hydrophobic and hydrophilic) can be encapsulated in different regions to avoid their interaction. The existence of the CaP shell can protect the DOX against free release and cause an increased transfer of DOX across membranes, overcoming multidrug resistance. Release studies from core-shell carriers showed the possibility of achieving sequential release of more than one type of drug by controlling the pH-sensitive CaP shell and degradable AG core. The highly pH-responsive behavior of the carrier can modulate the dual-drug-release of DOX/CPT, specifically in acidic intracellular pH environments. The AG/CPT@CaP-DOX nanoparticles also exhibited higher drug efficiencies against MCF-7/ADR cells than MCF-7 cells, thanks to a synergistic cell cycle arrest/apoptosis-inducing effect between CPT and DOX. As such, this core shell system can serve as a general platform for the localized, controlled, sequential delivery of multiple drugs to treat several diseases, especially for multidrug-resistant cancer cells. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Multifunctional nanocarriers for simultaneous encapsulation of hydrophobic and hydrophilic drugs in cancer treatment
(2014-01-01)
Su, Chia-Wei
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Chiang, Chih-Sheng
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Li, Wei-Ming
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Hu, Shang-Hsiu
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Chen, San-Yuan
Combination therapy for cancer patients is an important standard of care protocol because it can elicit synergistic therapeutic effects and reduce systemic toxicity by simultaneously modulating multiple cell-signaling pathways and overcoming multidrug resistance. Nanocarriers are expected to play a major role in delivering multiple drugs to tumor tissues by overcoming biological barriers. However, especially considering the different physical chemistry of chemotherapeutic drugs, it is highly desirable to develop a codelivery nanocarrier for controlled and targeted delivery of both hydrophobic and hydrophilic drugs. This review reports the recent developments in various combinational drug delivery systems and the simultaneous use of combinational drug delivery systems with functional agents.
Sodium Dodecyl Sulfate-Modified Doxorubicin-Loaded Chitosan-Lipid Nanocarrier with Multi Polysaccharide-Lecithin Nanoarchitecture for Augmented Bioavailability and Stability of Oral Administration In Vitro and In Vivo
(2016-05)
Su, Chia-Wei
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Chiang, Min-Yu
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Lin, Yu-Ling
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Tsai, Nu-Man
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Chen, Yen-Po
For oral anti-cancer drug delivery, a new chitosan-lipid nanoparticle with sodium dodecyl sulfate modification was designed and synthesized using a double emulsification. TEM examination showed that the DOX-loaded nanoparticles, termed D-PL/TG NPs, exhibited a unique core shell configuration composed of multiple amphiphilic chitosan-lecithin reverse micelles as the core and a triglyceride shell as a physical barrier to improve the encapsulation efficiency and reduce the drug leakage. In addition, the D-PL/TG NPs with sodium dodecyl sulfate modification on the surface have enhanced stability in the GI tract and increased oral bioavailability of doxorubicin. In vitro transport studies performed on Caco-2 monolayers indicated that the D-PL/TG NPs enhanced the permeability of DOX in the Caco-2 monolayers by altering the transport pathway from passive diffusion to transcytosis. The in vivo intestinal absorption assay suggested that the D-PL/TG NPs were preferentially absorbed through the specialized membranous epithelial cells (M cells) of the Peyer\'s patches, resulting in a significant improvement (8-fold) in oral bioavailability compared to that of free DOX. The experimental outcomes in this work demonstrate that the D-PL/TG NPs provide an exciting opportunity for advances in the oral administration of drugs with poor bioavailability that are usually used in treating tough and chronic diseases.
Synergistic combination therapy using a lipid shell-droplet core nanosphere with tunable thickness
(2014)
Su, Chia-Wei
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Fan, Ting-Hsi
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Li, Wei-Ming
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Chen, San-Yuan
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交大名義發表
A newly-designed drug carrier composed of an internal droplet core and a thickness-controllable shell was successfully developed. By co-delivering paclitaxel, doxorubicin and quantum dots simultaneously, this combinational drug delivery system could achieve in vitro fluorescence imaging, chemotherapeutic and oxidation therapy.
Using the interplay of magnetic guidance and controlled TGF-beta release from protein-based nanocapsules to stimulate chondrogenesis
(2018-01-01)
Chiang, Chih-Sheng
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Chen, Jian-Yi
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Chiang, Min-Yu
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Hou, Kai-Ting
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Li, Wei-Ming
Introduction: Stimulating the proliferation and differentiation of chondrocytes for the regeneration of articular cartilage is a promising strategy, but it is currently ineffective. Although both physical stimulation and growth factors play important roles in cartilage repair, their interplay remains unclear and requires further investigation. In this study, we aimed to clarify their contribution using a magnetic drug carrier that not only can deliver growth factors but also provide an external stimulation to cells in the two-dimensional environment. Materials and methods: We developed a nanocapsule ( transforming growth factor-beta 1 [TGF-beta 1]lo aded magnetic amphiphilic gelatin nanocapsules [MAGNCs]; TGF-beta 1@MAGNCs) composed of hexanoic-anhydride-grafted gelatin and iron oxide nanoparticles to provide a combination treatment of TGF-beta 1 and magnetically induced physical stimuli. With the expression of Arg-Gly-Asp peptide in the gelatin, the TGF-beta 1@MAGNCs have an inherent affinity for chondrogenic ATDC5 cells. Results: In the absence of TGF-beta 1, ATDC5 cells treated with a magnetic field show significantly upregulated Col2a1 expression. Moreover, TGF-beta 1 slowly released from biodegradable TGF-beta 1@MAGNCs further improves the differentiation with increased expression of Col2a1 and Aggrecan. Conclusion: Our study shows the time-dependent interplay of physical stimuli and growth factors on chondrogenic regeneration, and demonstrates the promising use of TGF-beta 1@MAGNCs for articular cartilage repair.