Influence of the formulation on the tolerance profile of nanoparticle-bound doxorubicin in healthy rats: Focus on cardio- and testicular toxicity

Переверзева, Э. Р.; Treschalin, I. D.; Bodyagin, D. A.; Maksimenko, Olga; Langer, Klaus; Dreis, Sebastian; Asmussen, B.; Kreuter, Jörg; Gelperina, Svetlana

doi:10.1016/j.ijpharm.2007.01.031

Cited by 71 publications

(38 citation statements)

References 33 publications

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“…Surfactants may cause damage to cell membranes of erythrocytes due to increases in membrane permeability [54] and therefore an in vitro erythrocyte toxicity test was carried out to evaluate biocompatibility of the nanoparticles [55] Triton-X-100 (positive control) showed 100% [32]. This might be due to micelle formation of the surfactant at the nanoparticle and water interface, resulting in solubilisation of the drug and stabilisation of the entire system.…”

Section: In Vitro Erythrocyte Toxicity Studymentioning

confidence: 99%

Bio-inspired artemether-loaded human serum albumin nanoparticles for effective control of malaria-infected erythrocytes

Sidhaye¹,

Bhuran²,

Zambare³

et al. 2016

Nanomedicine

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Aim: The intra-erythrocytic development of the malarial parasite is dependent on active uptake of nutrients, including human serum albumin (HSA), into parasitized red blood cells (pRBCs). We have designed HSA-based nanoparticles as a potential drug-delivery option for antimalarials. Methods: Artemether-loaded nanoparticles (AAN) were designed and antimalarial activity evaluated in-vitro/in-vivo using Plasmodium falciparum/Plasmodium berghei species, respectively. Results: Selective internalisation of AAN into Plasmodiuminfected RBCs in preference to healthy erythrocytes was observed using confocal-imaging.In-vitro studies showed 50% dose reduction for AAN as compared to drug-only controls to achieve IC50 levels of inhibition. The nanoparticles exhibited 2-fold higher peak drug concentrations in RBCs with antimalarial activity at 50% of therapeutic doses in P.bergeiinfected mice. Conclusion: HSA-based nanoparticles offer safe and effective approach for selective targeting of antimalarial drugs.

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Section: In Vitro Erythrocyte Toxicity Studymentioning

confidence: 99%

Bio-inspired artemether-loaded human serum albumin nanoparticles for effective control of malaria-infected erythrocytes

Sidhaye¹,

Bhuran²,

Zambare³

et al. 2016

Nanomedicine

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“…For acute toxicity the lethal dose 50 (LD50) or maximum tolerated dose (MTD) is used (Kim et al 2001;Kaminskas et al 2012;Larabi et al 2004). Whilst for specific organ toxicity, irregularities in organ function such as the glomerular filtration rate (GFR) for the kidneys (Mora et al 2003) or the QT interval for the heart can be measured (Pereverzeva et al 2007). Organ weights or total animal body weights compared to a control can also be useful indications of toxicity (Pereverzeva et al 2007;Injac et al 2008).…”

Section: Measuring Toxicitymentioning

confidence: 99%

Using random forest and decision tree models for a new vehicle prediction approach in computational toxicology

et al. 2015

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Drug vehicles are chemical carriers that provide beneficial aid to the drugs they bear. Taking advantage of their favourable properties can potentially allow the safer use of drugs that are considered highly toxic. A means for vehicle selection without experimental trial would therefore be of benefit in saving time and money for the industry. Although machine learning is increasingly used in predictive toxicology, to our knowledge there is no reported work in using machine learning techniques to model drug-vehicle relationships for vehicle selection to minimise toxicity. In this paper we demonstrate the use of data mining and machine learning techniques to process, extract and build models based on classifiers (decision trees and random forests) that allow us to predict which vehicle would be most suited to reduce a drug's toxicity. Using data acquired from the National Institute of Health's (NIH) Developmental Therapeutics Program (DTP) we propose a methodology using an area under a curve (AUC) approach that allows us to distinguish which vehicle provides the best toxicity profile for a drug and build classification models based on this knowledge. Our results show that we can achieve prediction accuracies of 80 % using random forest models whilst the decision tree models produce Communicated by D. Neagu. Electronic supplementary materialThe online version of this article (doi:10.1007/s00500-015-1925-9) contains supplementary material, which is available to authorized users.

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“…It is well known that several proteases such as serine proteases or cysteine proteases are produced by tumors. [26][27][28] Like proteinase K, proteases in tumor cells such as cathepsin B or matrix metalloproteinase may function to cleave crosslinking and to release drugs from nanoparticles. Langer and colleagues previously reported an equivalent or increased cytotoxicity of DXR-HSA NPs in neuroblastoma cell lines, UKF-NB3 and IMR 32 compared to free DXR.…”

Section: Discussionmentioning

confidence: 99%

“…17,[29][30][31] Using mice transplanted liver cancer cells, Miao et al showed that the tumor-suppressing effect of DXR-albumin NPs (diameter: 170 nm) was superior to that of DXR alone. 17) Using healthy rats, Pereverzeva et al suggested that DXR-HSA NPs (diameter: 404 nm) reduces cardio-and testicular toxicities observed in free DXR.…”

Section: Discussionmentioning

confidence: 99%

“…17) Using healthy rats, Pereverzeva et al suggested that DXR-HSA NPs (diameter: 404 nm) reduces cardio-and testicular toxicities observed in free DXR. 29) Polyak et al showed that 73 and 74% of the particles with the diameters of 176 and 429 nm, respectively were located in the liver 5 min after their administration and more than 50% of nanoparticles remained in the body, even after 22 h. 30) Furthermore, Farlander et al suggested that modifying the surface of nanoparticles by polyethylene glycol (PEG) could contribute to the extension of plasma half-life of drug-unloaded HSA nanoparticles (diameter; 140 nm). 31) Taking such previous in vivo data and our present data into consideration, the anthracycline-HSA NPs produced by the desolvation technique in present study would also be expected to show therapeutic effects against tumors.…”

Section: Discussionmentioning

confidence: 99%

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Preparation and <i>in Vitro</i> Analysis of Human Serum Albumin Nanoparticles Loaded with Anthracycline Derivatives

et al. 2018

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Nanoparticles prepared using human serum albumin (HSA) have emerged as versatile carriers for improving the pharmacokinetic profile of drugs. The desolvation of HSA using ethanol followed by stabilization through crosslinking with glutaraldehyde is a common technique for preparing HSA nanoparticles, but our knowledge concerning the characteristics (or functions) of HSA nanoparticles and their efficiency when loaded with drugs is limited. To address this issue in more detail, we prepared anthracycline-loaded HSA nanoparticles. Doxorubicin-loaded HSA nanoparticles with a size similar to doxorubicin-unloaded particles could be prepared by desolvating at a higher pH (8-9), and the size (100-150 nm) was optimum for delivery to tumor tissues. Using this procedure, HSA nanoparticles were loaded with other anthracycline derivatives, and all showed cytotoxicity in cancer cells. However, the efficiency of drug loading and dissolution rate were different among them possibly due to the differences in the type of association of the drugs on nanoparticles (doxorubicin and daunorubicin; covalently bound to nanoparticles, pirarubicin; both covalently bound to and adsorbed on nanoparticles, aclarubicin; adsorbed on nanoparticles). Since the formulation of such drug-loaded HSA nanoparticles should be modified for efficient delivery to tumors, the findings reported herein provide the useful information for optimizing the formulation and the production process for the HSA nanoparticles using a desolvation technique.

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Influence of the formulation on the tolerance profile of nanoparticle-bound doxorubicin in healthy rats: Focus on cardio- and testicular toxicity

Cited by 71 publications

References 33 publications

Bio-inspired artemether-loaded human serum albumin nanoparticles for effective control of malaria-infected erythrocytes

Bio-inspired artemether-loaded human serum albumin nanoparticles for effective control of malaria-infected erythrocytes

Using random forest and decision tree models for a new vehicle prediction approach in computational toxicology

Preparation and <i>in Vitro</i> Analysis of Human Serum Albumin Nanoparticles Loaded with Anthracycline Derivatives

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