Intravenous tolerance of a nanoparticle-based formulation of doxorubicin in healthy rats

Переверзева, Э. Р.; Treschalin, I. D.; Bodyagin, D. A.; Maksimenko, Olga; Kreuter, Jörg; Gelperina, Svetlana

doi:10.1016/j.toxlet.2008.01.020

Cited by 43 publications

(19 citation statements)

References 18 publications

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“…Consistent with our current study, recent studies have shown encouraging results using other animal models, e.g. Pereverzeva et al evaluating the intravenous tolerance of nanoparticle-based formulation of doxorubicin in healthy rats and pointed out that the employment of the nanoparticles exhibits a more favorable safety profile (32). Furthermore, Tang et al used the HPLC to evaluate the tissue distribution of the free doxorubincin and micelle-encapsulated doxorubicin (M-Dox) and concluded that the mean doxorubicin concentrations 12 h after injection of doxorubicin in heart, liver, lung, spleen, and kidney of mice treated with M-Dox (10 mg/kg) are much lower than free doxorubicin (10 mg/kg) (33).…”

Section: Discussionsupporting

confidence: 91%

Antitumor activity of monomethoxy poly(ethylene glycol)-poly (ε-caprolactone) micelle-encapsulated doxorubicin against mouse melanoma

Qian¹

2011

Oncol Rep

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Abstract. Doxorubicin (Dox) is one of the most commonly used and highly effective antineoplastic agents, but the clinical application of this broad spectrum drug is largely hampered by its poor stability and serious toxicity to normal tissues. Hence, it is essential to improve the therapeutic effect and decrease the systematic toxicity for the administration of doxorubicin. In our study, doxorubicin was incorporated into monomethoxy poly(ethylene glycol)-poly(Â-caprolactone) (MPEG-PCL) micelle by a self-assembly method. The cytotoxicity and cellular uptake efficiency of Dox-loaded MPEG-PCL (Dox/MPEG-PCL) micelle against B16-F10 murine melanoma cells was examined by the methylthiazoltetrazolium (MTT) test and flow cytometry. The antitumor activity of Dox/MPEG-PCL was evaluated in C57BL/6 mice injected subcutaneously with B16-F10 cells. Toxicity was evaluated in tumor-free mice. Meanwhile, tumor proliferation, intratumoal angiogenesis and apoptotic cells were evaluated by PCNA, CD31 staining and TUNEL assay, respectively. Encapsulation of doxorubicin in MPEG-PCL micelle improved the cytotoxicity of doxorubicin and enhanced its cellular uptake on B16-F10 cell in vitro. Administration of Dox/MPEG-PCL micelle resulted in significant inhibition (75% maximum inhibition relative to controls) in the growth of B16-F10 tumor xenografts and prolonged the survival of the treated mice (P<0.05). These anti-tumor responses were associated with marked increase of tumor apoptosis and notable reduction of cell proliferation and intratumoral microvessel density (P<0.05). The system toxicity also decreased in the Dox/MPEG-PCL group compared with free doxorubicin group. Our data indicate that the encapsulation of doxorubicin in MPEG-PCL micelle improved the anti-tumor activity in vivo without conspicuous systemic toxic effects.

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Section: Discussionsupporting

confidence: 91%

Antitumor activity of monomethoxy poly(ethylene glycol)-poly (ε-caprolactone) micelle-encapsulated doxorubicin against mouse melanoma

Qian¹

2011

Oncol Rep

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“…According to the previous reports, free DOX administration caused heart damage, swollen cardiac muscle fibers, interstitial edema and inflammatory infiltration [45,46]. As seen in Fig.…”

Section: Anti-tumor Efficacy Of Dox-loaded Nanopolymersomesmentioning

confidence: 62%

The chemotherapeutic potential of doxorubicin-loaded PEG-b-PLGA nanopolymersomes in mouse breast cancer model

Alibolandi

Sadeghi

Abnous

et al. 2015

European Journal of Pharmaceutics and Biopharmaceutics

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“…5). Studies have shown that histological evidence of organ toxicity can be observed postinjection within days (31,32). In this study, a thorough examination of H&E-stained organ sections did not reveal any significant signs of toxicity.…”

Section: Resultsmentioning

confidence: 99%

In vivo prevention of arterial restenosis with paclitaxel-encapsulated targeted lipid–polymeric nanoparticles

Chan

Rhee

Drum

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

130

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Following recent successes with percutaneous coronary intervention (PCI) for treating coronary artery disease (CAD), many challenges remain. In particular, mechanical injury from the procedure results in extensive endothelial denudation, exposing the underlying collagen IV-rich basal lamina, which promotes both intravascular thrombosis and smooth muscle proliferation. Previously, we reported the engineering of collagen IV-targeting nanoparticles (NPs) and demonstrated their preferential localization to sites of arterial injury. Here, we develop a systemically administered, targeted NP system to deliver an antiproliferative agent to injured vasculature. Approximately 60-nm lipid-polymeric NPs were surface functionalized with collagen IV-targeting peptides and loaded with paclitaxel. In safety studies, the targeted NPs showed no signs of toxicity and a ≥3.5-fold improved maximum tolerated dose versus paclitaxel. In efficacy studies using a rat carotid injury model, paclitaxel (0.3 mg/kg or 1 mg/kg) was i.v. administered postprocedure on days 0 and 5. The targeted NP group resulted in lower neointima-to-media (N/M) scores at 2 wk versus control groups of saline, paclitaxel, or nontargeted NPs. Compared with sham-injury groups, an ∼50% reduction in arterial stenosis was observed with targeted NP treatment. The combination of improved tolerability, sustained release, and vascular targeting could potentially provide a safe and efficacious option in the management of CAD. P ercutaneous coronary interventions (PCIs) using drug-eluting stents (DESs) are credited with significant reductions in vessel restenosis, due to the effective combination of a drug delivery system and mechanical scaffold (1). Despite the extensive clinical use of DESs to maintain vascular patency, not all coronary lesions are amenable to DES placement (2). In addition, DESs are associated with delayed endothelialization (3) and increased thrombogenicity (4, 5) that require extended antiplatelet treatment (6). In some cases, only bare metal stents (BMSs) may be applied, which lack the benefit of antirestenotic therapy and instead stimulate neointimal smooth muscle cell (SMC) proliferation (7,8).Nanomedicines may offer improvements to existing clinical treatments, including those for cardiovascular disorders (9, 10). Sub-100-nm organic nanoparticles (NPs) combine useful features of ultrasmall size (11, 12), surface modification (13), controlled drug release, biodegradability, and biocompatibility (14). Liposomal, polymeric, and albumin-based NPs have been formulated to improve drug solubility and deliver paclitaxel at doses higher than otherwise possible in circulation (15-17). Temporal control of drug delivery may facilitate endothelial healing after injury, as NPs may be used to deliver antiproliferative agents to the vascular wall when neointimal proliferation is most active, followed by complete degradation and clearance (18). Targeted NPs that bind to exposed antigens in injured arteries may help to achieve therapeutic doses at sites of injury, b...

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Intravenous tolerance of a nanoparticle-based formulation of doxorubicin in healthy rats

Cited by 43 publications

References 18 publications

Antitumor activity of monomethoxy poly(ethylene glycol)-poly (ε-caprolactone) micelle-encapsulated doxorubicin against mouse melanoma

Antitumor activity of monomethoxy poly(ethylene glycol)-poly (ε-caprolactone) micelle-encapsulated doxorubicin against mouse melanoma

The chemotherapeutic potential of doxorubicin-loaded PEG-b-PLGA nanopolymersomes in mouse breast cancer model

In vivo prevention of arterial restenosis with paclitaxel-encapsulated targeted lipid–polymeric nanoparticles

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