PRCosomes: pretty reactive complexes formed in liposomes

Wehbe, Mohamed; Chernov, Lina; Chen, Kent; Bally, Marcel B.

doi:10.1080/1061186x.2016.1186169

Cited by 21 publications

(12 citation statements)

References 70 publications

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“…We confirmed that quercetin exhibits limited aqueous solubility despite heating the mixtures to 60°C (solubility is 12.33 μg/mL in water (60°C) and 38 μg/mL in HBS (60°C); data not shown). As described previously, the ability to form copper-quercetin within copper-containing liposomes is dependent on quercetin permeation across the liposomal lipid bilayer and this process is influenced by temperature [23]. Further, the rate of copper-quercetin complex formation is also likely temperature-dependent.…”

Section: Formation Of Copper-quercetin Within Copper-containing Dspc/mentioning

confidence: 71%

“…If a suitable intravenous formulation of quercetin was developed, issues related to bioavailability would then be addressed and perhaps suitable concentrations of quercetin in the blood could be obtained. We recently described a formulation method for poorly soluble drugs, including flavonoids like quercetin, that considers the use of compounds that can coordinate metals and nanotechnology [23]. In this report, liposomal formulations prepared based on quercetin-copper binding have been characterized.…”

Section: Discussionmentioning

confidence: 99%

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Characterization of a liposomal copper(II)-quercetin formulation suitable for parenteral use

Chen

Anantha

Leung

et al. 2019

Drug Deliv. and Transl. Res.

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Quercetin (3,3′,4′,5,7-pentahydroxyflavone) is a naturally derived flavonoid that is commonly found in fruits and vegetables. There is mounting evidence to suggest that quercetin has potential anticancer effects and appears to interact synergistically when used in combination with approved chemotherapeutic agents such as irinotecan and cisplatin. Unfortunately, quercetin has shown limited clinical utility, partly due to low bioavailability related to its poor aqueous solutions (< 10 μg/mL). In this study, liposomal formulations of quercetin were developed by exploiting quercetin's ability to bind copper. Quercetin powder was added directly to pre-formed copper-containing liposomes (2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and cholesterol (CHOL) (55:45 M ratio)). As a function of time and temperature, the formation of copper-quercetin was measured. Using this methodology, a final quercetin-to-lipid (mol:mol) ratio of 0.2 was achievable and solutions containing quercetin at concentrations of > 5 mg/mL were attained, representing at least a > 100-fold increase in apparent solubility. The resulting formulation was suitable for intravenous dosing with no overt toxicities when administered at doses of 50 mg/kg in mice. Pharmacokinetic studies demonstrated that the copper-quercetin formulations had an AUC 0-24H of 8382.1 μg h/mL when administered to mice at 50 mg/kg. These studies suggested that quercetin (not copper-quercetin) dissociates from the liposomes after administration. The resulting formulation is suitable for further development and also serves as a proof-of-concept for formulating other flavonoids and flavonoid-like compounds. Given that quercetin exhibits an IC 50 of >10 μM when tested against cancer cell lines, we believe that the utility of this novel quercetin formulation for cancer indications will ultimately be as a component of a combination product.

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Section: Formation Of Copper-quercetin Within Copper-containing Dspc/mentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Characterization of a liposomal copper(II)-quercetin formulation suitable for parenteral use

Chen

Anantha

Leung

et al. 2019

Drug Deliv. and Transl. Res.

Self Cite

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“…Additionally, polymers like poly(lactic acid) nanoparticles (183), superparamagnetic iron oxide nanoparticles (184), and mesoporous silica nanoparticles (185) have all been shown to encapsulate quercetin. Additionally, a quercetin-encapsulated liposomal product was successfully developed in our lab using a metal complexation technology that enhanced quercetin’s circulation longevity and improved its apparent solubility (186). Thus, it would be of particular interest to see if these formulations can be used to encapsulate flavopiridol to increase the therapeutic potential of the drug.…”

Section: Nanoparticulate Formulations For Flavopiridolmentioning

confidence: 99%

Recent Treatment Advances and the Role of Nanotechnology, Combination Products, and Immunotherapy in Changing the Therapeutic Landscape of Acute Myeloid Leukemia

Chen

Gilabert-Oriol²,

Bally

et al. 2019

Pharm Res

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Acute myeloid leukemia (AML) is the most common acute leukemia that is becoming more prevalent particularly in the older (65 years of age or older) population. For decades, “7 + 3” remission induction therapy with cytarabine and an anthracycline, followed by consolidation therapy, has been the standard of care treatment for AML. This stagnancy in AML treatment has resulted in less than ideal treatment outcomes for AML patients, especially for elderly patients and those with unfavourable profiles. Over the past two years, six new therapeutic agents have received regulatory approval, suggesting that a number of obstacles to treating AML have been addressed and the treatment landscape for AML is finally changing. This review outlines the challenges and obstacles in treating AML and highlights the advances in AML treatment made in recent years, including Vyxeos®, midostaurin, gemtuzumab ozogamicin, and venetoclax, with particular emphasis on combination treatment strategies. We also discuss the potential utility of new combination products such as one that we call “EnFlaM”, which comprises an encapsulated nanoformulation of flavopiridol and mitoxantrone. Finally, we provide a review on the immunotherapeutic landscape of AML, discussing yet another angle through which novel treatments can be designed to further improve treatment outcomes for AML patients.

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“…This transition metal-complexation technology has further evolved through works completed by the Bally’s group, who is now working with other founders (Ada Leung and Thomas Redelmeier), the Vice President of research (Michael Abrams), and the entrepreneurial group at UBC (e@UBC and HATCH) to lead the development of what is referred to as Metaplex technology. The Metaplex technology is an active loading platform wherein a transition metal ion gradient is established across the membrane and used as the primary driving force to accumulate drugs inside liposomes; drugs that exhibit limited water solubility, may not contain a protonizable amine, but do contain a metal binding function [60,61]. In this technology, there is clear evidence that the selected drug has a metal binding function.…”

Section: Optimization Of Liposomes For Pharmaceutical Usementioning

confidence: 99%

What Drives Innovation: The Canadian Touch on Liposomal Therapeutics

et al. 2019

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Liposomes are considered one of the most successful drug delivery systems (DDS) given their established utility and success in the clinic. In the past 40–50 years, Canadian scientists have made ground-breaking discoveries, many of which were successfully translated to the clinic, leading to the formation of biotech companies, the creation of research tools, such as the Lipex Extruder and the NanoAssemblr™, as well as contributing significantly to the development of pharmaceutical products, such as Abelcet®, MyoCet®, Marqibo®, Vyxeos®, and Onpattro™, which are making positive impacts on patients’ health. This review highlights the Canadian contribution to the development of these and other important liposomal technologies that have touched patients. In this review, we try to address the question of what drives innovation: Is it the individual, the teams, the funding, and/or an entrepreneurial spirit that leads to success? From this perspective, it is possible to define how innovation will translate to meaningful commercial ventures and products with impact in the future. We begin with a brief history followed by descriptions of drug delivery technologies influenced by Canadian researchers. We will discuss recent advances in liposomal technologies, including the Metaplex technology from the author’s lab. The latter exemplifies how a nanotechnology platform can be designed based on multidisciplinary groups with expertise in coordination chemistry, nanomedicines, disease, and business to create new therapeutics that can effect better outcomes in patient populations. We conclude that the team is central to the effort; arguing if the team is entrepreneurial and well positioned, the funds needed will be found, but likely not solely in Canada.

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PRCosomes: pretty reactive complexes formed in liposomes

Cited by 21 publications

References 70 publications

Characterization of a liposomal copper(II)-quercetin formulation suitable for parenteral use

Characterization of a liposomal copper(II)-quercetin formulation suitable for parenteral use

Recent Treatment Advances and the Role of Nanotechnology, Combination Products, and Immunotherapy in Changing the Therapeutic Landscape of Acute Myeloid Leukemia

What Drives Innovation: The Canadian Touch on Liposomal Therapeutics

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