Altering the intra-liver distribution of phospholipid-free small unilamellar vesicles using temperature-dependent size-tunability

Vogler, Julian; Böttger, Roland; Fayez, Nojoud Al; Zhang, Wunan; Zhu, Qi; Hohenwarter, Lukas; Chao, Po-Han; Rouhollahi, Elham; Bilal, Nida; Chen, Naliangzi; Lee, Brandon; Chen, Christine; Wilkinson, Brayden; Kieffer, Timothy J.; Kulkarni, Jayesh A.; Cullis, Pieter R.; Witzigmann, Dominik; Li, Shyh-Dar

doi:10.1016/j.jconrel.2021.03.025

Cited by 9 publications

(8 citation statements)

References 41 publications

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“…9 Our data showed that PFSUVs fabricated using the staggered herringbone mixer (SHM) microfluidic system with a 5:1 molar ratio of Chol/Tween80 displayed predominant accumulation in the liver. 12 In this study, we further demonstrated that within the liver, PFSUVs selectively accumulated in the hepatocytes as soon as 2 h post injection. As shown in Figure 1, the hepatocytes (indicated by arrow 1) can be identified through the phalloidin staining and their distinct nuclear morphology from the Kupffer cells (indicated by arrow 2), and approximately ∼70% of DiR-labeled PFSUVs were detected within the hepatocytes.…”

Section: ■ Results and Discussionsupporting

confidence: 65%

“…delivery . Our data showed that PFSUVs fabricated using the staggered herringbone mixer (SHM) microfluidic system with a 5:1 molar ratio of Chol/Tween80 displayed predominant accumulation in the liver . In this study, we further demonstrated that within the liver, PFSUVs selectively accumulated in the hepatocytes as soon as 2 h post injection.…”

Section: Results and Discussionsupporting

confidence: 51%

“…This delivery system is composed of cholesterol and Tween80, hence the name “phospholipid-free” to differentiate from standard liposomal SUVs that are made of phospholipids. Although there have been many different nanoparticles developed for drug delivery, the vast majority of them were captured by the Kupffer cells and eliminated. , Here, we report the utilization of this formulation for targeting PQ to the liver with reduced RBC exposure and toxicity. We fabricated the particles using microfluidics and optimized the active loading protocol for PQ with detailed characterizations of the final formulation.…”

Section: Introductionmentioning

confidence: 99%

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Improved Liver Delivery of Primaquine by Phospholipid-Free Small Unilamellar Vesicles with Reduced Hemolytic Toxicity

et al. 2021

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Hemolytic toxicity caused by primaquine (PQ) is a high-risk condition that hampers the wide use of PQ to treat liverstage malaria. This study demonstrated that phospholipid-free small unilamellar vesicles (PFSUVs) composed of Tween80 and cholesterol could encapsulate and deliver PQ to the hepatocytes with reduced exposure to the red blood cells (RBCs). Nonionic surfactant (Tween80) and cholesterol-forming SUVs with a mean diameter of 50 nm were fabricated for delivering PQ. Drug release/ retention, drug uptake by RBCs, pharmacokinetics, and liver uptake of PFSUVs-PQ were evaluated in in vitro and in vivo models in comparison to free drugs. Additionally, the stress effect on RBCs induced by free PQ and PFSUVs-PQ was evaluated by examining RBC morphology. PFSUVs provided >95% encapsulation efficiency for PQ at a drug-to-lipid ratio of 1:20 (w/w) and stably retained the drug in the presence of serum. When incubated with RBCs, PQ uptake in the PFSUVs group was reduced by 4-to 8-folds compared to free PQ. As a result, free PQ induced significant RBC morphology changes, while PFSUVs-PQ showed no such adverse effect. Intravenously (i.v.) delivered PFSUVs-PQ produced a comparable plasma profile as free PQ, given i.v. and orally, while the liver uptake was increased by 4.8 and 1.6-folds, respectively, in mice. Within the liver, PFSUVs selectively targeted the hepatocytes, with no significant blood or liver toxicity in mice. PFSUVs effectively targeted PQ to the liver and reduced RBC uptake compared to free PQ, leading to reduced RBC toxicity. PFSUVs exhibited potential in improving the efficacy of PQ for treating liver-stage malaria.

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Section: ■ Results and Discussionsupporting

confidence: 65%

Section: Results and Discussionsupporting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

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Improved Liver Delivery of Primaquine by Phospholipid-Free Small Unilamellar Vesicles with Reduced Hemolytic Toxicity

et al. 2021

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“…We previously developed an innovative niosomal delivery system comprising of 75–83 mol% Chol and 17–25 mol% TWEEN 80, a nonionic surfactant. , Weak-base amphipathic compounds actively loaded into the niosomes were rapidly and effectively delivered to the hepatocytes, making it a promising drug delivery system for improving treatment of liver diseases. , Here, we passively incorporated Cur, a phytotherapeutic with antioxidant and anti-inflammatory effects, into the niosomes (Nio-Cur) and developed and employed a HPLC-UV/vis-ELS method to characterize the products during the formulation optimization stage.…”

Section: Resultsmentioning

confidence: 99%

Simultaneous Chromatographic Quantitation of Drug Substance and Excipients in Nanoformulations Using a Combination of Evaporative Light Scattering and Absorbance Detectors

et al. 2022

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Nanomedicines including lipid-and polymer-based nanoparticles and polymer−drug conjugates enable targeted drug delivery for the treatment of numerous diseases. Quantitative analysis of components in nanomedicines is routinely performed to characterize the products to ensure quality and property consistency but has been mainly focused on the active pharmaceutical ingredients (APIs) in academic publications. It has been increasingly recognized that excipients in nanomedicines are critical in determining the product quality, stability, consistency, and safety. APIs are often analyzed by highperformance liquid chromatography (HPLC), and it would be convenient if the same method can be applied to excipients to robustly quantify all components in nanomedicines. Here, we report the development of a HPLC method that combined an evaporative light scattering (ELS) detector with an UV−vis detector to simultaneously analyze drugs and excipients in nanomedicines. This method was tested on diverse nanodrug delivery systems, including a niosomal nanoparticle encapsulating a phytotherapeutic, a liposome encapsulating an immune boosting agent, and a PEGylated peptide. This method can be utilized for a variety of applications, such as monitoring drug loading, studying drug release, and storage stability. The information obtained from the analyses is of importance for nanomedicine formulation development.

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“…Several studies have utilized this platform to synthesize various NPs such as liposomes, LNPs, oil-in-water nanoemulsions, and unilamellar vesicles. [42][43][44][45]…”

Section: Staggered Herringbone Micromixingmentioning

confidence: 99%

Microfluidic Nanoparticles for Drug Delivery

Liu

Yang

Hui

et al. 2022

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Nanoparticles (NPs) have attracted tremendous interest in drug delivery in the past decades. Microfluidics offers a promising strategy for making NPs for drug delivery due to its capability in precisely controlling NP properties. The recent success of mRNA vaccines using microfluidics represents a big milestone for microfluidic NPs for pharmaceutical applications, and its rapid scaling up demonstrates the feasibility of using microfluidics for industrial‐scale manufacturing. This article provides a critical review of recent progress in microfluidic NPs for drug delivery. First, the synthesis of organic NPs using microfluidics focusing on typical microfluidic methods and their applications in making popular and clinically relevant NPs, such as liposomes, lipid NPs, and polymer NPs, as well as their synthesis mechanisms are summarized. Then, the microfluidic synthesis of several representative inorganic NPs (e.g., silica, metal, metal oxide, and quantum dots), and hybrid NPs is discussed. Lastly, the applications of microfluidic NPs for various drug delivery applications are presented.

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Altering the intra-liver distribution of phospholipid-free small unilamellar vesicles using temperature-dependent size-tunability

Cited by 9 publications

References 41 publications

Improved Liver Delivery of Primaquine by Phospholipid-Free Small Unilamellar Vesicles with Reduced Hemolytic Toxicity

Improved Liver Delivery of Primaquine by Phospholipid-Free Small Unilamellar Vesicles with Reduced Hemolytic Toxicity

Simultaneous Chromatographic Quantitation of Drug Substance and Excipients in Nanoformulations Using a Combination of Evaporative Light Scattering and Absorbance Detectors

Microfluidic Nanoparticles for Drug Delivery

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