Macromolecular complexes of drugs. I. Doxorubicin-heparin complex.

Aoyama, Toshinobu; Horioka, Masayoshi; Nagamitsu, S.

doi:10.1248/cpb.35.808

Cited by 15 publications

(7 citation statements)

References 1 publication

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“…In summary, in silico modelling showed that the heparin component of the cryogel microcarriers plays a crucial role in their drug loading capacity and is expected to directly impact the long and steady release of doxorubicin. These data are in accordance with previous studies showing doxorubicin binding to heparin or heparin hydrogels (Aoyama, Horioka, & Nagamitsu, 1987;Li, Ye, Zhang, & Feng, 2019;Wen et al, 2020;Yu et al, 2019). Here, the PEG region has only a marginal role in the doxorubicin-microcarrier interaction, suggesting that specifically heparin-based microcarriers can be an efficient drug delivery platform for doxorubicin.…”

Section: In Silico Drug Loading: Doxorubicin Preferentially Binds To Heparinsupporting

confidence: 92%

Focal drug administration via heparin-containing cryogel microcarriers reduces cancer growth and metastasis

Newland

Varricchio

Körner

et al. 2020

Carbohydrate Polymers

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Developing drug delivery systems that release anticancer drugs in a controlled and sustained manner remains challenging. We hypothesized that highly sulfated heparinbased microcarriers would allow electrostatic drug binding and controlled release. In silico modelling showed that the anticancer drug doxorubicin has affinity for the heparin component of the microcarriers. Experimental results showed that the strong electrostatic interaction was reversible, allowing both doxorubicin loading and a subsequent slow release over 42 days without an initial burst release. The drug-loaded microcarriers were able to reduce cancer cell viability in vitro in both hormone-dependent and highly aggressive triple-negative human breast cancer cells. Focal drug treatment, of an in vivo orthotopic triple-negative breast cancer model significantly decreased tumor burden and reduced cancer metastasis, whereas systemic administration of an equivalent drug dose was ineffective. This study proves that heparin-based microcarriers can be used as drug delivery platforms, for focal delivery and sustained longterm drug release.

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Section: In Silico Drug Loading: Doxorubicin Preferentially Binds To Heparinsupporting

confidence: 92%

Focal drug administration via heparin-containing cryogel microcarriers reduces cancer growth and metastasis

Newland

Varricchio

Körner

et al. 2020

Carbohydrate Polymers

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“…By increasing the β-sheet content, these hydrophobic domains provide more adsorption sites [33]. In addition to providing hydrophobic adsorption sites, the negative net charge of silk is also expected to contribute to drug binding, analogous to that observed in doxorubicin-heparin complexes [34]. The desorption of doxorubicin from silk was greatest in the 4°C water annealed silk films, which further supports the idea that β-sheet content regulates doxorubicin-silk interactions and kinetics.…”

Section: Discussionmentioning

confidence: 74%

Doxorubicin-loaded silk films: Drug-silk interactions and in vivo performance in human orthotopic breast cancer

2012

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Breast cancer is the most common of all malignant diseases in women. Systemic chemotherapy provides low clinical benefit for locoregional control of the disease, while localised chemotherapy may provide a therapeutic advantage. In this study, doxorubicin-loaded silk films were directly applied to tumours. Affinity binding studies demonstrated that the adsorption of doxorubicin onto silk was partially dependent on crystallinity. By manipulating silk crystallinity, or β-sheet content, the doxorubicin release rate could be controlled ranging from immediate release to prolonged release over >4 weeks. Following successful in vitro studies, the therapeutic impact of doxorubicin-loaded silk films on primary tumour growth and metastasis was assessed in mice using a humanised orthotopic breast cancer model (adenocarcinoma). Both soluble and stabilised silk films loaded with doxorubicin had a significantly greater primary tumour response than the equivalent dose of doxorubicin administered intravenously in the absence of the silk film carrier. In addition to reducing primary tumour growth, stabilised silk films loaded with doxorubicin also reduced metastatic spread and autopsy indicated that these films were not associated with any local or systemic toxicities. Collectively, these results suggest that the future use of this approach for localised chemotherapy is promising.

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“…Besides, the negative net charge of SF also contributes to the positively charged DOX binding. These properties enable DOX to diffuse through SF NPs Figure A describes the release behaviors of DOX from DSF-NPs and DSF@Z-NPs.…”

Section: Results and Discussionmentioning

confidence: 99%

Biomimetic Nucleation of Metal–Organic Frameworks on Silk Fibroin Nanoparticles for Designing Core–Shell-Structured pH-Responsive Anticancer Drug Carriers

Chen

Yang

et al. 2021

ACS Appl. Mater. Interfaces

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Silk fibroin (SF) is a biomacromolecule that can be assembled into nanostructures and induce biomimetic nucleation of inorganic materials. Zeolitic imidazolate framework-8 (ZIF-8), a metal–organic framework (MOF), can be dissolved selectively under acidic pH. Here, we integrated SF and ZIF-8 to develop novel drug carriers that selectively release drug in the acidic intracellular environment of cancer cells. Specifically, SF was assembled into nanoparticles (SF-NPs), which were then loaded with an antitumor drug, doxorubicin (DOX), to form DSF-NPs. Due to the SF-mediated organization of ZIF-8 precursors such as zinc ions, the DSF-NPs further templated the nucleation of ZIF-8 onto their surface to generate core–shell-structured NPs (termed DSF@Z-NPs) with ZIF-8 as a shell and DSF-NP as a core. We found that the DSF@Z-NPs, highly stable under neutral conditions, could be uptaken by breast cancer cells, release DOX selectively owing to dissolution of ZIF-8 shells in the acidic intracellular environment in a controlled manner, and induce cell apoptosis. We also confirmed that the DSF@Z-NPs could inhibit tumor growth more efficiently to reach a higher survival rate than their controls by inducing cell apoptosis in vivo. Our study suggests that SF and MOF could be combined to design a new type of cancer therapeutics.

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Macromolecular complexes of drugs. I. Doxorubicin-heparin complex.

Cited by 15 publications

References 1 publication

Focal drug administration via heparin-containing cryogel microcarriers reduces cancer growth and metastasis

Focal drug administration via heparin-containing cryogel microcarriers reduces cancer growth and metastasis

Doxorubicin-loaded silk films: Drug-silk interactions and in vivo performance in human orthotopic breast cancer

Biomimetic Nucleation of Metal–Organic Frameworks on Silk Fibroin Nanoparticles for Designing Core–Shell-Structured pH-Responsive Anticancer Drug Carriers

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