In vivo toxicological evaluation of polymeric nanocapsules after intradermal administration

Bulcão, Rachel Picada; Freitas, Fernando Monteiro de; Dallegrave, Eliane; Venturini, Cristina G.; Baierle, Marília; Durgante, Juliano; Saüer, Elisa; Cassini, Carina; Cerski, Carlos Thadeu Schmidt; Zielinsky, Paulo; Salvador, Mirian; Pohlmann, Adriana Raffin; Guterres, Sílvia Stanisçuaski; Garcia, Solange Cristina

doi:10.1016/j.ejpb.2013.04.001

Cited by 36 publications

(26 citation statements)

References 43 publications

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“…The doses were five-times higher than the doses used in our previous studies with Wistar rats, [21][22][23] because our purpose was the potential treatment against acute intoxication, when high doses of antidotes are necessary to reverse symptoms quickly. It was observed that increasing the dose of LNC/mL led to an increase in mortality rate in the nematodes.…”

Section: Caenorhabditis Elegans As An Alternative In Vivo Modelmentioning

confidence: 97%

“…20,54 In vitro and in vivo studies reported that the large surface area of NPs results in a high reactivity, which could lead to cytotoxicity. 16,[20][21][22]54 The NPs' properties such as chemical composition, shape, size, surface chemistry, and large surface reactivity are mainly responsible for the possible toxicological effects caused by NPs. 16,21,22 Thus, although the present work did not explore different physical and chemical characteristics of nanocapsules, this alternative model is recommended for toxicological screening because it allows a systematic evaluation of many particularities of nanomaterials, yielding rapid and accurate results.…”

Section: Caenorhabditis Elegans As An Alternative In Vivo Modelmentioning

confidence: 99%

“…These toxicity data are in agreement with our previous studies with Wistar rats, which demonstrated no toxic effects or death after acute and subchronic intraperitoneal and intradermal administration of LNC. 21,22 Another toxicity endpoint used to verify potential toxic effects of LNC was the evaluation of the worm development, which was monitored by measuring body area. Because growth of C. elegans is determined by a conservative genetic regulatory pathway, this endpoint test is a good parameter to evaluate toxic effects in C. elegans.…”

Section: Caenorhabditis Elegans As An Alternative In Vivo Modelmentioning

confidence: 99%

“…Previous studies from our research group have evaluated acute and subchronic LNC toxicity in rats after intraperitoneal and intradermal administration, whose results showed the safety of this promising drug delivery system. [21][22][23] However, the great number of new nanomaterials requires the use of in vivo models to provide the toxicological screening, 24 and following the three Rs policy (to reduce, replace, and refine the animals used for this purpose) is important, 25 especially with alternative in vivo models.…”

Section: Introductionmentioning

confidence: 99%

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Caenorhabditis elegans as an alternative in vivo model to determine oral uptake, nanotoxicity, and efficacy of melatonin-loaded lipid-core nanocapsules on paraquat damage

Charão

Souto

Brucker

et al. 2015

IJN

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Caenorhabditis elegans is an alternative in vivo model that is being successfully used to assess the pharmacological and toxic effects of drugs. The exponential growth of nanotechnology requires the use of alternative in vivo models to assess the toxic effects of theses nanomaterials. The use of polymeric nanocapsules has shown promising results for drug delivery. Moreover, these formulations have not been used in cases of intoxication, such as in treatment of paraquat (PQ) poisoning. Thus, the use of drugs with properties improved by nanotechnology is a promising approach to overcome the toxic effects of PQ. This research aimed to evaluate the absorption of rhodamine B-labeled melatonin (Mel)-loaded lipid-core nanocapsules (LNC) by C. elegans , the application of this model in nanotoxicology, and the protection of Mel-LNC against PQ damage. The formulations were prepared by self-assembly and characterized by particle sizing, zeta potential, drug content, and encapsulation efficiency. The results demonstrated that the formulations had narrow size distributions. Rhodamine B-labeled Mel-LNC were orally absorbed and distributed in the worms. The toxicity assessment of LNC showed a lethal dose 50% near the highest dose tested, indicating low toxicity of the nanocapsules. Moreover, pretreatment with Mel-LNC significantly increased the survival rate, reduced the reactive oxygen species, and maintained the development in C. elegans exposed to PQ compared to those worms that were either untreated or pretreated with free Mel. These results demonstrated for the first time the uptake and distribution of Mel-LNC by a nematode, and indicate that while LNC is not toxic, Mel-LNC prevents the effects of PQ poisoning. Thus, C. elegans may be an interesting alternative model to test the nanocapsules toxicity and efficacy.

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Section: Caenorhabditis Elegans As An Alternative In Vivo Modelmentioning

confidence: 97%

Section: Caenorhabditis Elegans As An Alternative In Vivo Modelmentioning

confidence: 99%

Section: Caenorhabditis Elegans As An Alternative In Vivo Modelmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Caenorhabditis elegans as an alternative in vivo model to determine oral uptake, nanotoxicity, and efficacy of melatonin-loaded lipid-core nanocapsules on paraquat damage

Charão

Souto

Brucker

et al. 2015

IJN

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“…Moreover, it is well demonstrated that the LNC formulation has no potential for either acute or sub-chronic toxicity in vivo. 32,33 The loading of MTX on LNC provides a stable pharmaceutical formulation with a high concentration in inflammatory sites.…”

Section: Discussionmentioning

confidence: 99%

Methotrexate-loaded lipid-core nanocapsules are highly effective in the control of inflammation in synovial cells and a chronic arthritis model

Boechat¹,

Oliveira

Tarragô³

et al. 2015

IJN

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Background Rheumatoid arthritis (RA) is the most common autoimmune disease in the word, affecting 1% of the population. Long-term prognosis in RA was greatly improved following the introduction of highly effective medications such as methotrexate (MTX). Despite the importance of this drug in RA, 8%–16% of patients must discontinue the treatment because of adverse effects. Last decade, we developed a promising new nanocarrier as a drug-delivery system, lipid-core nanocapsules. Objective The aim of the investigation reported here was to evaluate if methotrexate-loaded lipid-core nanocapsules (MTX-LNC) reduce proinflammatory and T-cell-derived cytokines in activated mononuclear cells derived from RA patients and even in functional MTX-resistant conditions. We also aimed to find out if MTX-LNC would reduce inflammation in experimentally inflammatory arthritis at lower doses than MTX solution. Methods Formulations were prepared by self-assembling methodology. The adjuvant arthritis was induced in Lewis rats (AIA) and the effect on edema formation, TNF-α levels, and interleukin-1 beta levels after treatment was evaluated. Mononuclear cells obtained from the synovial fluid of RA patients during articular infiltration procedures were treated with MTX solution and MTX-LNC. For in vitro experiments, the same dose of MTX was used in comparing MTX and MTX-LNC, while the dose of MTX in the MTX-LNC was 75% lower than the drug in solution in in vivo experiments. Results Formulations presented nanometric and unimodal size distribution profiles, with D[4.3] of 175±17 nm and span of 1.6±0.2. Experimental results showed that MTX-LNC had the same effect as MTX on arthritis inhibition on day 28 of the experiment ( P <0.0001); however, this effect was achieved earlier, on day 21 ( P <0.0001), by MTX-LNC, and this formulation had reduced both TNF-α ( P =0.001) and IL-1α ( P =0.0002) serum levels by the last day of the experiment. Further, the MTX-LNC were more effective at reducing the cytokine production from mononuclear synovial cells than MTX. Conclusion The MTX-LNC were better than the MTX solution at reducing proinflammatory cytokines and T-cell-derived cytokines such as interferon-gamma and interleukin-17A. This result, combined with the reduction in the dose required for therapy, shows that MTX-LNC are a very promising system for the treatment of RA.

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Improving drug biological effects by encapsulation into polymeric nanocapsules

Frank

Contri

Beck

et al. 2015

WIREs Nanomed Nanobiotechnol

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130

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This review is based on selected reports from 2004 to 2014 and provides a comprehensive and updated overview of the state of the art related to the drug delivery advantages of polymeric nanocapsules, which are a specific type of polymeric nanoparticles used for improvement of biological effects. Special attention is given to the application of nanocapsules to increase the chemical and photostability of drugs, to modulate the interaction with cells and tissues, to reduce adverse effects of drugs, and to increase the drug efficiency and/or bioavailability. Moreover, this review covers in vitro and in vivo studies, highlighting interesting examples of drugs from several therapeutic classes for which efficacy is improved by encapsulation in different types of nanocapsules, especially in lipid-core nanocapsules. We also briefly present the first results obtained so far attesting to the safety of using polymeric nanocapsules for drug delivery.

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In vivo toxicological evaluation of polymeric nanocapsules after intradermal administration

Cited by 36 publications

References 43 publications

Caenorhabditis elegans as an alternative in vivo model to determine oral uptake, nanotoxicity, and efficacy of melatonin-loaded lipid-core nanocapsules on paraquat damage

Caenorhabditis elegans as an alternative in vivo model to determine oral uptake, nanotoxicity, and efficacy of melatonin-loaded lipid-core nanocapsules on paraquat damage

Methotrexate-loaded lipid-core nanocapsules are highly effective in the control of inflammation in synovial cells and a chronic arthritis model

Improving drug biological effects by encapsulation into polymeric nanocapsules

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In vivo toxicological evaluation of polymeric nanocapsules after intradermal administration

Cited by 36 publications

References 43 publications

Caenorhabditis elegans as an alternative in vivo model to determine oral uptake, nanotoxicity, and efficacy of melatonin-loaded lipid-core nanocapsules on paraquat damage

Caenorhabditis elegans as an alternative in vivo model to determine oral uptake, nanotoxicity, and efficacy of melatonin-loaded lipid-core nanocapsules on paraquat damage

Methotrexate-loaded lipid-core nanocapsules are highly effective in the control of inflammation in&nbsp;synovial cells and a chronic arthritis model

Improving drug biological effects by encapsulation into polymeric nanocapsules

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Methotrexate-loaded lipid-core nanocapsules are highly effective in the control of inflammation in synovial cells and a chronic arthritis model