Dataset Information

Cancer Nanomedicines Stabilized by ?-? Stacking between Heterodimeric Prodrugs Enable Exceptionally High Drug Loading Capacity and Safer Delivery of Drug Combinations.

ABSTRACT: Combination therapy using distinct mode-of-action drugs has sparked a rapidly growing interest because this paradigm holds promise for improving the therapeutic efficacy of anticancer therapy. However, the current drug combination therapy refers to administering individual drugs together, which is far from a perfect regimen for cancer patients. The aim of this work was to demonstrate that synergistic delivery of two chemotherapeutic drugs in a single nanoparticle reservoir could be achieved through the rational chemical ligation of the drugs followed by supramolecular nano-assembly via blending of the drugs with a minimal amount of matrix. Choosing 7-ethyl-10-hydroxycamptothecin and taxanes, which are rich in aromatic structures, as model compounds, we show that the heterodimeric conjugates of the two agents are miscible with lipids to form systemically injectable nanomedicines. The compatibility between the prodrug conjugates and lipid carriers is substantially augmented by the intermolecular ?-? stacking and alleviated polarity, thus enabling an exceptionally high drug loading (DL) capacity (~92%) and a gratifyingly long drug retention time within the micellar core. We further observed superior therapeutic outcomes in a mouse tumor model without detecting accompanying systemic toxicity. This structure-based, self-assembled cancer nanomedicine increased the potency and drug tolerability in animals and thus offers a robust strategy for simultaneously formulating two or more drugs in single nanovehicles.

SUBMITTER: Wang H

PROVIDER: S-EPMC5667338 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Cancer Nanomedicines Stabilized by π-π Stacking between Heterodimeric Prodrugs Enable Exceptionally High Drug Loading Capacity and Safer Delivery of Drug Combinations.

Wang Hangxiang H Chen Jianmei J Xu Chang C Shi Linlin L Tayier Munire M Zhou Jiahui J Zhang Jun J Wu Jiaping J Ye Zhijian Z Fang Tao T Han Weidong W

Theranostics 20170823 15

Combination therapy using distinct mode-of-action drugs has sparked a rapidly growing interest because this paradigm holds promise for improving the therapeutic efficacy of anticancer therapy. However, the current drug combination therapy refers to administering individual drugs together, which is far from a perfect regimen for cancer patients. The aim of this work was to demonstrate that synergistic delivery of two chemotherapeutic drugs in a single nanoparticle reservoir could be achieved thro ...[more]

PMID: 29109766

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Project description:BackgroundInternet-sourced drugs are often considered suspect. The World Health Organization reports that drugs from websites that conceal their physical address are counterfeit in over 50 percent of cases; the U.S. Food and Drug Administration (FDA) works with the National Association of Boards of Pharmacy (NABP) to regularly update a list of websites likely to sell drugs that are illegal or of questionable quality.Methods and findingsThis study examines drug purchasing over the Internet, by comparing the sales of five popular drugs from a selection of websites stratified by NABP or other ratings. The drugs were assessed for price, conditions of purchase, and basic quality. Prices and conditions of purchase varied widely. Some websites advertised single pills while others only permitted the purchase of large quantities. Not all websites delivered the exact drugs ordered, some delivered no drugs at all; many websites shipped from multiple international locations, and from locations that were different from those advertised on the websites. All drug samples were tested against approved U.S. brand formulations using Raman spectrometry. Many (17) websites substituted drugs, often in different formulations from the brands requested. These drugs, some of which were probably generics or perhaps non-bioequivalent copy versions, could not be assessed accurately. Of those drugs that could be assessed, none failed from "approved", "legally compliant" or "not recommended" websites (0 out of 86), whereas 8.6% (3 out of 35) failed from "highly not recommended" and unidentifiable websites.ConclusionsOf those drugs that could be assessed, all except Viagra(R) passed spectrometry testing. Of those that failed, few could be identified either by a country of manufacture listed on the packaging, or by the physical location of the website pharmacy. If confirmed by future studies on other drug samples, then U.S. consumers should be able to reduce their risk by relying on credentialing agencies recommended lists and by using common sense when examining packaging and pills.

Dataset Information

Cancer Nanomedicines Stabilized by ?-? Stacking between Heterodimeric Prodrugs Enable Exceptionally High Drug Loading Capacity and Safer Delivery of Drug Combinations.

Publications

Cancer Nanomedicines Stabilized by π-π Stacking between Heterodimeric Prodrugs Enable Exceptionally High Drug Loading Capacity and Safer Delivery of Drug Combinations.

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