Polymeric nanocapsules as a technological alternative to reduce the toxicity caused by meloxicam in mice

Villalba, Benonio T.; Ianiski, Francine R.; Vogt, Ane G.; Pinz, Mikaela P.; Reis, Angélica S.; Vaucher, Rodrigo de Almeida; Soares, Mauro Pereira; Wilhelm, Ethel A.

doi:10.1016/j.yrtph.2016.09.023

Cited by 12 publications

(6 citation statements)

References 28 publications

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“…In contrast to previous reports, 38 NSAID-related pathology such as gastrointestinal ulceration or liver or kidney damage was not observed in our cohort. Gastric ulceration, gastritis, and inflammation of the liver was reported in Swiss mice given 10 mg/kg PO meloxicam for 5 d, 38 suggesting that subcutaneous administration of 20 mg/kg meloxicam may be safer than oral administration of the same dose. Saline-injected mice did display some pathology, including mild localized inflammation at the site of injection.…”

Section: Discussioncontrasting

confidence: 99%

“…Available toxicity data involving commonly used NSAID predominantly use the oral route of administration. Swiss mice displayed gastric ulceration after receiving 10 mg/kg meloxicam by gavage once daily for 5 d. 38 However, a single dose of 20 mg/kg meloxicam given by gavage to male C57BL/6J mice did not induce any NSAID-related toxicity in gastrointestinal, renal, or hepatic tissues. 13 In another study, mice displayed gastrointestinal ulceration at meloxicam doses of 17.5 to 35 mg/kg PO given once daily for 3 mo; no renal or hepatic toxicity was seen at these doses.…”

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confidence: 96%

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Concentration-dependent Toxicity after Subcutaneous Administration of Meloxicam to C57BL/6N Mice (Mus musculus)

Sarfaty

Zeiss

Willis

et al. 2019

j am assoc lab anim sci

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Studies using the Mouse Grimace Scale have shown that for many NSAID, including meloxicam, minimal doses of at least 20 mg/kg may be necessary to achieve adequate peri- and post-operative analgesia in mice. However, more data are needed to determine whether such NSAID doses exceed the threshold for gastrointestinal ulceration or induce other relevant pathology. We administered equal volumes of saline or injectable meloxicam (1 or 5 mg/mL) at a dose of 20 mg/kg SC to 20 young adult male and female C57BL/6N mice daily for 6 d and performed necropsies on all mice on the seventh day. Mice given 5 mg/mL meloxicam subcutaneously developed significantly more severe pathology at the injection site than saline controls. Pathology was characterized by full-thickness epidermal necrosis; cavitary lesions within subcutis, muscle, or fat; steatitis; and myositis. Mice that received 1 mg/mL meloxicam subcutaneously developed lesions that were qualitatively similar but far less severe than those after 5 mg/mL. However, no pathologic lesions typically associated with NSAID toxicity, such as gastric ulceration and liver and kidney lesions, were seen. These results demonstrate that although meloxicam injected subcutaneously causes concentration-dependent skin pathology at the injection site, a dose of 20 mg/kg can be safely administered subcutaneously at a concentration of 1 mg/mL for as long as 6 d.

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Section: Discussioncontrasting

confidence: 99%

mentioning

confidence: 96%

Concentration-dependent Toxicity after Subcutaneous Administration of Meloxicam to C57BL/6N Mice (Mus musculus)

Sarfaty

Zeiss

Willis

et al. 2019

j am assoc lab anim sci

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“…SO-NC formulations were prepared by a simple and fast method [21] . Data concerning to the physicochemical properties of the SO-NC showed high encapsulation efficiency, size distribution between 200 and 300 nm, and negative zeta potential value, which are in accordance with the literature for polymeric nanocapsules [23] , [25] . In addition, SO-NC demonstrated maintenance of size and PdI below 0.3 for 28 days when stored at 4 °C.…”

Section: Discussionsupporting

confidence: 89%

“…NC have been used for different purposes, among them increasing the dispersibility of oils and lipophilic molecules [23] , [24] , reduce drug toxicity [25] , protect the encapsulated substance against inactivation [24] , control drug release [23] , [26] , and increase therapeutic efficacy after oral administration [27] .…”

Section: Introductionmentioning

confidence: 99%

Lecithin-based nanocapsule loading sucupira (Pterodon emarginatus) oil effects in experimental mucositis

Miceli

Andrade²,

Carvalho³

et al. 2022

Toxicology Reports

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“…In the case of NSAIDs, reduced effects at the stomach are especially advantageous as this helps to reduce the stomach ulcers and bleeding which can be caused by NSAID use (Table 2). 4–25…”

Section: Systemic Targeting And/or Encapsulationmentioning

confidence: 99%

Localized and targeted delivery of NSAIDs for treatment of inflammation: A review

Haley

Recum

2018

Exp Biol Med (Maywood)

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Inflammatory processes are increasingly being identified at the core of many different disease states (e.g. heart disease, cancer, diabetes). As such, anti-inflammatory strategies available through drug delivery have undergone renewed interest. Due to the systemic side effects of steroidal drugs, non-steroidal anti-inflammatory drugs are often preferred for long-term treatment of inflammation in a variety of applications. While non-steroidal anti-inflammatory drugs are generally safe, there are some serious side effects that can be associated with their usage, particularly when given systemically or orally. Due to the high number of patients taking non-steroidal anti-inflammatory drugs, the reduction or elimination of these side effects, such as is possible through local drug delivery, could have a very powerful effect on patient quality of life. This review comments on a sampling of existing methods for localized or targeted delivery of non-steroidal anti-inflammatory drugs, with the goal of helping future research groups to focus on bettering methods shown to be effective and filling the gaps of knowledge in this field. Additionally, commentary is made on the field as a whole, and the standardization issues that arise from its expansiveness and diversity. Impact statement This work provides an overview of research currently being done exploring potential drug delivery device strategies for NSAIDs as an alternative to systemic delivery. Commentary on this field is made in an attempt to aid future experimental design, enabling researchers to determine the drugs and delivery vehicles which are most advantageous for them to pursue, as well as suggestions to standardize the reporting of such future research.

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Polymeric nanocapsules as a technological alternative to reduce the toxicity caused by meloxicam in mice

Cited by 12 publications

References 28 publications

Concentration-dependent Toxicity after Subcutaneous Administration of Meloxicam to C57BL/6N Mice (Mus musculus)

Concentration-dependent Toxicity after Subcutaneous Administration of Meloxicam to C57BL/6N Mice (Mus musculus)

Lecithin-based nanocapsule loading sucupira (Pterodon emarginatus) oil effects in experimental mucositis

Localized and targeted delivery of NSAIDs for treatment of inflammation: A review

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