An injectable, thermosensitive and multicompartment hydrogel for simultaneous encapsulation and independent release of a drug cocktail as an effective combination therapy platform

Wang, Weiwei; Song, Huijuan; Zhang, Ju; Li, Pan; Li, Chen; Wang, Chun; Kong, Deling; Zhao, Qiang

doi:10.1016/j.jconrel.2015.02.015

Cited by 79 publications

(57 citation statements)

References 54 publications

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“…11,99–101 As the liposomes constituted a structural component of the hybrid hydrogels, we anticipated that the multicomponent network would offer opportunities for dual encapsulation and differential release of multiple therapeutic cargo molecules. To examine the potential suitability of these hybrid hydrogels for such applications, cytochrome c, a small mitochondrial protein (~12 kDa) that can initiate an apoptotic cascade leading to programmed cell death upon cytoplasmic release, 102–105 was chosen as a second therapeutic molecule.…”

Section: Resultsmentioning

confidence: 99%

Liposome-Cross-Linked Hybrid Hydrogels for Glutathione-Triggered Delivery of Multiple Cargo Molecules

Liang¹,

Kiick

2016

Biomacromolecules

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Novel, liposome-cross-linked hybrid hydrogels cross-linked by the Michael-type addition of thiols with maleimides were prepared via the use of maleimide-functionalized liposome cross-linkers and thiolated polyethylene glycol (PEG) polymers. Gelation of the materials was confirmed by oscillatory rheology experiments. These hybrid hydrogels are rendered degradable upon exposure to thiol-containing molecules such as glutathione (GSH), via the incorporation of selected thioether succinimide cross-links between the PEG polymers and liposome nanoparticles. Dynamic light scattering (DLS) characterization confirmed that intact liposomes were released upon network degradation. Owing to the hierarchical structure of the network, multiple cargo molecules relevant for chemotherapies, namely doxorubicin (DOX) and cytochrome c, were encapsulated and simultaneously released from the hybrid hydrogels, with differential release profiles that were driven by degradation-mediated release and Fickian diffusion, respectively. This work introduces a facile approach for the development of advanced, hybrid drug delivery vehicles that exhibit novel chemical degradation.

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Section: Resultsmentioning

confidence: 99%

Liposome-Cross-Linked Hybrid Hydrogels for Glutathione-Triggered Delivery of Multiple Cargo Molecules

Liang¹,

Kiick

2016

Biomacromolecules

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“…An in-vivo study showed improved antitumor activity over free drugs via enhanced accumulation of the nanocarriers in the tumor site. A thermosensitive, multi-compartment, and injectable hydrogel was engineered using assembly of PEGylated fluorocarbon and PEGylated hydrocarbon nanoparticles [180]. The injectable material incorporated PTX and DOX separately and released simultaneously to achieve a synergistic effect in vitro and in vivo in human breast carcinoma cells and xenograft mouse models, respectively.…”

Section: Optimal Design Of Delivery Systems For Combination Therapymentioning

confidence: 99%

“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

Kemp

Shim

Heo

et al. 2016

Advanced Drug Delivery Reviews

440

258

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a b s t r a c t a r t i c l e i n f oThe dynamic and versatile nature of diseases such as cancer has been a pivotal challenge for developing efficient and safe therapies. Cancer treatments using a single therapeutic agent often result in limited clinical outcomes due to tumor heterogeneity and drug resistance. Combination therapies using multiple therapeutic modalities can synergistically elevate anti-cancer activity while lowering doses of each agent, hence, reducing side effects. Co-administration of multiple therapeutic agents requires a delivery platform that can normalize pharmacokinetics and pharmacodynamics of the agents, prolong circulation, selectively accumulate, specifically bind to the target, and enable controlled release in target site. Nanomaterials, such as polymeric nanoparticles, gold nanoparticles/cages/shells, and carbon nanomaterials, have the desired properties, and they can mediate therapeutic effects different from those generated by small molecule drugs (e.g., gene therapy, photothermal therapy, photodynamic therapy, and radiotherapy). This review aims to provide an overview of developing multi-modal therapies using nanomaterials ("combo" nanomedicine) along with the rationale, up-to-date progress, further considerations, and the crucial roles of interdisciplinary approaches.

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“…After being entrapped by various nanosized vehicles, [1][2][3][4] the circulation time of therapeutic agents was prolonged, and the concentration of drugs accumulated into tumor sites was enhanced owing to the enhanced permeability and retention effect. 5,6 However, the nanocarrier for this drug delivery system is still confronted with a series of barriers when applied to antitumor activities in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

Folic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors

Zhou¹,

Yang²,

Wang³

et al. 2016

IJN

Self Cite

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Although the shortcomings of small molecular antitumor drugs were efficiently improved by being entrapped into nanosized vehicles, premature drug release and insufficient tumor targeting demand innovative approaches that boost the stability and tumor responsiveness of drug-loaded nanocarriers. Here, we show the use of the core cross-linking method to generate a micelle with enhanced drug encapsulation ability and sensitivity of drug release in tumor. This kind of micelle could increase curcumin (Cur) delivery to HeLa cells in vitro and improve tumor accumulation in vivo. We designed and synthesized the core cross-linked micelle (CCM) with polyethylene glycol and folic acid-polyethylene glycol as the hydrophilic units, pyridyldisulfide as the cross-linkable and hydrophobic unit, and disulfide bond as the cross-linker. CCM showed spherical shape with a diameter of 91.2 nm by the characterization of dynamic light scattering and transmission electron microscope. Attributed to the core cross-linking, drug-loaded CCM displayed higher Nile Red or Cur-encapsulated stability and better sensitivity to glutathione than noncross-linked micelle (NCM). Cellular uptake and in vitro antitumor studies proved the enhanced endocytosis and better cytotoxicity of CCM-Cur against HeLa cells, which had a high level of glutathione. Meanwhile, the folate receptor-mediated drug delivery (FA-CCM-Cur) further enhanced the endocytosis and cytotoxicity. Ex vivo imaging studies showed that CCM-Cur and FA-CCM-Cur possessed higher tumor accumulation until 24 hours after injection. Concretely, FA-CCM-Cur exhibited the highest tumor accumulation with 1.7-fold of noncross-linked micelle Cur and 2.8-fold of free Cur. By combining cross-linking of the core with active tumor targeting of FA, we demonstrated a new and effective way to design nanocarriers for enhanced drug encapsulation, smart tumor responsiveness, and elevated tumor accumulation.

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An injectable, thermosensitive and multicompartment hydrogel for simultaneous encapsulation and independent release of a drug cocktail as an effective combination therapy platform

Cited by 79 publications

References 54 publications

Liposome-Cross-Linked Hybrid Hydrogels for Glutathione-Triggered Delivery of Multiple Cargo Molecules

Liposome-Cross-Linked Hybrid Hydrogels for Glutathione-Triggered Delivery of Multiple Cargo Molecules

“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

Folic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors

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