Sistemas coloidais SNEDDS carreadores de Croton cajucara Benth aplicados em modelos experimentais in vivo de antinocicepção, inflamação e cicatrização dérmica
Life sciences-based technology has enabled new treatments including the expansion of the bioavailability of drugs with reduction of adverse effects. Chronic inflammatory diseases (ICD) and chronic wounds, for example, are widely treated effectively, but the adverse effects attributed to medicatio...
Na minha lista:
| Autor principal: | |
|---|---|
| Outros Autores: | |
| Formato: | doctoralThesis |
| Idioma: | pt_BR |
| Publicado em: |
Universidade Federal do Rio Grande do Norte
|
| Assuntos: | |
| Endereço do item: | https://repositorio.ufrn.br/handle/123456789/48256 |
| Tags: |
Adicionar Tag
Sem tags, seja o primeiro a adicionar uma tag!
|
| id |
ri-123456789-48256 |
|---|---|
| record_format |
dspace |
| institution |
Repositório Institucional |
| collection |
RI - UFRN |
| language |
pt_BR |
| topic |
Croton cajucara Benth Óleo fixo Transdesidrocrotonina Nanoencapsulamento SNEDDS Atividades antinociceptiva e anti-inflamatória Cicatrização dérmica |
| spellingShingle |
Croton cajucara Benth Óleo fixo Transdesidrocrotonina Nanoencapsulamento SNEDDS Atividades antinociceptiva e anti-inflamatória Cicatrização dérmica Medeiros, Magnaldo Inácio Tavares Sistemas coloidais SNEDDS carreadores de Croton cajucara Benth aplicados em modelos experimentais in vivo de antinocicepção, inflamação e cicatrização dérmica |
| description |
Life sciences-based technology has enabled new treatments including the expansion of the
bioavailability of drugs with reduction of adverse effects. Chronic inflammatory diseases (ICD) and
chronic wounds, for example, are widely treated effectively, but the adverse effects attributed to
medications limit prolonged treatment. Among the many possibilities of drug carriers, colloidal
systems stand out as an important strategy in the protection and targeted delivery of bioactive
products. Systemic chronic inflammation (SCI) and chronic wounds, for example, have been widely
treated, but the adverse effects attributed to medications limit prolonged treatments. In this present
study Croton cajucara Benth medicinal species was applied as an alternative therapy, by using in
vivo models, aiming at to analyze its nociception, inflammation and dermal wound healing. In that,
were used the non-volatil oil (so called fixed oil, FO) and the diterpine trans-dehydrocrotonin,
obtained from this herbal stem bark, were loaded into a colloidal self-nanoemulsion drug delivery
system (SNEDDS-type). The study was conducted aiming at the reduction of therapeutic doses and
toxic risks, maintenance of the constant level of the drug in the blood (by slow and controlled
release), and prolonged efficacy of therapeutic effects. The experimental study was carried out in
different stages, such as: chromatographic study to obtain the bioactives OF and t-DCTN,
development of a polar colloidal nanosystem O/A (oil in water), cotensoactive free, based on
surfactant mixture of Tween 80 and 40, a vegetable oil of food use (as the oil phase), and the
bioactives FO and t-DCTN, and then pharmacological applications. The SNEDDS-derivatives were
so called SNEDDS-OFCC (15 mg of fixed oil, rich in sesquiterpenes) and SNEDDS-DCTN (5 mg of
t-DCTN). The target SNEDDS system (bioactives free) was characterized by physicochemical
analyses and showed droplet diameter with reduced scale (11 nm). These nanobioproducts were
administered orally in experimental pain models through abdominal contortions and formalin tests.
In the models of inflammation (paw edema and peritonitis) dexamethasone (0.5 mg/kg, s.c.) was
used as positive control. SNEDDS-DCTN was assayed on experimental healing model, administered
topically in Wistar rat lesions (7, 14 and 21 days). For each experimental group, the retraction index
(morphometry) of the lesion and the tissue behavior (histopathological and immunohistochemical
analysis) were observed. The treatment results of SNEDDS-OFCC formulation showed 40.2%
inhibition in central pain (neuropathic) and 42.8% in inhibition of peripheral inflammatory pain.
Meanwhile, SNEDDS-DCTN in reducing abdominal contortions was effective in 76.7%, and in the
formalin test inhibited 47.9% (neuropathic pain) and 52.6% (peripheral pain). The inhibitor rates of
leukocyte migration (by carrageenan-induced inflammation) showed significant reductions for the
peritoneal cavity, with inhibitions 29.4% for SNEDDS-OFCC and 38% for SNEDDS-DCTN, in relation
to the negative control group (vehicle). In the paw edema inhibition, 89.7% was observed for
SNEDDS-DCTN. Based on these data, the SNEDDS-DCTN system was used in the experimental
healing model and showed lesion retraction on the 14th day was quantitative (98.3%), compared to
43.7% for the 7th day, and also to the negative control group. The histopathological analyses sowed
reduction in inflammation, with significant gains in cell proliferation and tissue maturation, compared
to the control group. Since the target SNEDDS is a system of cosurfactant free, it reinforces the
proposal of pharmacological application on prolonged periods, due to the reduction in the number of
the carrier ingredients and also by loading minimized concentrations of the bioactives of C. cajucara.
SNEDDS-OF and SNEDDS-DCTN presented associated antinociceptive and anti-inflammatory
action, as well as healing (SNEDDS-DCTN), so, they may meet a specific demand from patients
who are on prolonged treatments (SCI-type) to combat pain and inflammation caused by skin lesions
or chronic inflammations. |
| author2 |
Maciel, Maria Aparecida Medeiros |
| author_facet |
Maciel, Maria Aparecida Medeiros Medeiros, Magnaldo Inácio Tavares |
| format |
doctoralThesis |
| author |
Medeiros, Magnaldo Inácio Tavares |
| author_sort |
Medeiros, Magnaldo Inácio Tavares |
| title |
Sistemas coloidais SNEDDS carreadores de Croton cajucara Benth aplicados em modelos experimentais in vivo de antinocicepção, inflamação e cicatrização dérmica |
| title_short |
Sistemas coloidais SNEDDS carreadores de Croton cajucara Benth aplicados em modelos experimentais in vivo de antinocicepção, inflamação e cicatrização dérmica |
| title_full |
Sistemas coloidais SNEDDS carreadores de Croton cajucara Benth aplicados em modelos experimentais in vivo de antinocicepção, inflamação e cicatrização dérmica |
| title_fullStr |
Sistemas coloidais SNEDDS carreadores de Croton cajucara Benth aplicados em modelos experimentais in vivo de antinocicepção, inflamação e cicatrização dérmica |
| title_full_unstemmed |
Sistemas coloidais SNEDDS carreadores de Croton cajucara Benth aplicados em modelos experimentais in vivo de antinocicepção, inflamação e cicatrização dérmica |
| title_sort |
sistemas coloidais snedds carreadores de croton cajucara benth aplicados em modelos experimentais in vivo de antinocicepção, inflamação e cicatrização dérmica |
| publisher |
Universidade Federal do Rio Grande do Norte |
| publishDate |
2022 |
| url |
https://repositorio.ufrn.br/handle/123456789/48256 |
| work_keys_str_mv |
AT medeirosmagnaldoinaciotavares sistemascoloidaissneddscarreadoresdecrotoncajucarabenthaplicadosemmodelosexperimentaisinvivodeantinocicepcaoinflamacaoecicatrizacaodermica |
| _version_ |
1773962756499701760 |
| spelling |
ri-123456789-482562022-06-21T21:01:50Z Sistemas coloidais SNEDDS carreadores de Croton cajucara Benth aplicados em modelos experimentais in vivo de antinocicepção, inflamação e cicatrização dérmica Medeiros, Magnaldo Inácio Tavares Maciel, Maria Aparecida Medeiros http://lattes.cnpq.br/6820195618816346 http://lattes.cnpq.br/5360188002708095 Nascimento, José Heriberto Oliveira do https://orcid.org/0000-0001-6804-2854 http://lattes.cnpq.br/7033735079037677 Albuquerque Júnior, Ricardo Luiz Cavalcanti de Silva, Terezinha Gonçalves da Veiga Júnior, Valdir Florêncio da Croton cajucara Benth Óleo fixo Transdesidrocrotonina Nanoencapsulamento SNEDDS Atividades antinociceptiva e anti-inflamatória Cicatrização dérmica Life sciences-based technology has enabled new treatments including the expansion of the bioavailability of drugs with reduction of adverse effects. Chronic inflammatory diseases (ICD) and chronic wounds, for example, are widely treated effectively, but the adverse effects attributed to medications limit prolonged treatment. Among the many possibilities of drug carriers, colloidal systems stand out as an important strategy in the protection and targeted delivery of bioactive products. Systemic chronic inflammation (SCI) and chronic wounds, for example, have been widely treated, but the adverse effects attributed to medications limit prolonged treatments. In this present study Croton cajucara Benth medicinal species was applied as an alternative therapy, by using in vivo models, aiming at to analyze its nociception, inflammation and dermal wound healing. In that, were used the non-volatil oil (so called fixed oil, FO) and the diterpine trans-dehydrocrotonin, obtained from this herbal stem bark, were loaded into a colloidal self-nanoemulsion drug delivery system (SNEDDS-type). The study was conducted aiming at the reduction of therapeutic doses and toxic risks, maintenance of the constant level of the drug in the blood (by slow and controlled release), and prolonged efficacy of therapeutic effects. The experimental study was carried out in different stages, such as: chromatographic study to obtain the bioactives OF and t-DCTN, development of a polar colloidal nanosystem O/A (oil in water), cotensoactive free, based on surfactant mixture of Tween 80 and 40, a vegetable oil of food use (as the oil phase), and the bioactives FO and t-DCTN, and then pharmacological applications. The SNEDDS-derivatives were so called SNEDDS-OFCC (15 mg of fixed oil, rich in sesquiterpenes) and SNEDDS-DCTN (5 mg of t-DCTN). The target SNEDDS system (bioactives free) was characterized by physicochemical analyses and showed droplet diameter with reduced scale (11 nm). These nanobioproducts were administered orally in experimental pain models through abdominal contortions and formalin tests. In the models of inflammation (paw edema and peritonitis) dexamethasone (0.5 mg/kg, s.c.) was used as positive control. SNEDDS-DCTN was assayed on experimental healing model, administered topically in Wistar rat lesions (7, 14 and 21 days). For each experimental group, the retraction index (morphometry) of the lesion and the tissue behavior (histopathological and immunohistochemical analysis) were observed. The treatment results of SNEDDS-OFCC formulation showed 40.2% inhibition in central pain (neuropathic) and 42.8% in inhibition of peripheral inflammatory pain. Meanwhile, SNEDDS-DCTN in reducing abdominal contortions was effective in 76.7%, and in the formalin test inhibited 47.9% (neuropathic pain) and 52.6% (peripheral pain). The inhibitor rates of leukocyte migration (by carrageenan-induced inflammation) showed significant reductions for the peritoneal cavity, with inhibitions 29.4% for SNEDDS-OFCC and 38% for SNEDDS-DCTN, in relation to the negative control group (vehicle). In the paw edema inhibition, 89.7% was observed for SNEDDS-DCTN. Based on these data, the SNEDDS-DCTN system was used in the experimental healing model and showed lesion retraction on the 14th day was quantitative (98.3%), compared to 43.7% for the 7th day, and also to the negative control group. The histopathological analyses sowed reduction in inflammation, with significant gains in cell proliferation and tissue maturation, compared to the control group. Since the target SNEDDS is a system of cosurfactant free, it reinforces the proposal of pharmacological application on prolonged periods, due to the reduction in the number of the carrier ingredients and also by loading minimized concentrations of the bioactives of C. cajucara. SNEDDS-OF and SNEDDS-DCTN presented associated antinociceptive and anti-inflammatory action, as well as healing (SNEDDS-DCTN), so, they may meet a specific demand from patients who are on prolonged treatments (SCI-type) to combat pain and inflammation caused by skin lesions or chronic inflammations. A utilização da tecnologia baseada nas ciências biológicas tem possibilitado novos tratamentos como por exemplo, a ampliação da biodisponibilidade de fármacos e a redução de efeitos adversos. Dentre muitas possibilidades de carreadores de fármacos têm destaque os sistemas coloidais como estratégia importante na proteção e entrega direcionada de produtos bioativos. As doenças inflamatórias crônicas (DICs) e as feridas crônicas, por exemplo, são amplamente tratadas com eficácia, porém, os efeitos adversos atribuídos aos medicamentos limitam o tratamento prolongado. No presente estudo, utilizou-se a espécie medicinal Croton cajucara Benth aplicada em modelos experimentais in vivo, como terapia alternativa. Os bioativos utilizados, óleo fixo (OF) e o diterpeno trans-desidrocrotonina (t-DCTN), obtidos das cascas do caule deste vegetal, foram encapsulados em um sistema coloidal carreador do tipo SNEDDS (self-nanoemulsion drug delivery system), objetivando-se redução de doses terapêuticas e riscos tóxicos, a manutenção do nível constante do fármaco no sangue (pela liberação lenta e controlada), e a eficácia prolongada dos efeitos terapêuticos. O estudo experimental foi realizado em diferentes etapas, tais como: estudo cromatográfico para obtenção dos bioativos OF e t-DCTN; obtenção do nanosistema coloidal polar O/A (óleo em água), isento de cotensoativo, preparado com Tweens (80 e 40) como fase tensoativa, um óleo vegetal de uso alimentício (fase óleo), e os bioativos OFCC e DCTN; e aplicação dos bioprodutos em modelos experimentais in vivo de nocicepção, inflamação e cicatrização dérmica. Os SNEDDS-derivativos foram denominados SNEDDS-OFCC (15 mg de óleo fixo, rico em sesquiterpenos) e SNEDDS-DCTN (3 mg e 5 mg de t-DCTN). O sistema SNEDDS-branco (isento dos bioativos) foi caracterizado por análises físico-químicas e mostrou diâmetro de gotícula com escala reduzida (11 nm). Estes nanosistemas foram administrados por via oral, em modelos experimentais de dor através dos testes das contorções abdominais e da formalina. Nos modelos de inflamação (edema de pata e peritonite) a dexametasona (0,5 mg/kg, s.c.) foi utilizada como controle positivo. SNEDDS-DCTN foi utilizado no modelo experimental de cicatrização, administrado por via tópica em lesões de ratos Wistar (7, 14 e 21 dias). Para cada grupo experimental foi observado o índice de retração (morfometria) da lesão e o comportamento tecidual (análise histopatológica e imuno-histoquímica). Os resultados do tratamento com SNEDDS-OFCC mostraram 40,2% de inibição na dor de origem central (neuropática) e 42,8% na inibição da dor inflamatória periférica. SNEDDS-DCTN na redução das contorções abdominais foi efetivo em 76,7%, e no teste da formalina inibiu 47,9% (dor neuropática) e 52,6% (dor periférica). As taxas de inibições da migração leucocitária (inflamação induzida por carragenina), mostraram reduções significativas para a cavidade peritoneal, com inibições 29,4% para SNEDDS-OFCC e 38% para SNEDDS-DCTN, em relação ao grupo controle negativo (veículo). Na inibição do edema de pata observou-se 89,7% para SNEDDS-DCTN. Com base nestes resultados, o sistema SNEDDS-DCTN foi avaliado em modelo experimental de cicatrização e mostrou índice de retração das lesões no 14º dia quantitativo (98,3%), contra 43,7% para o 7º dia, em comparação ao grupo controle negativo. Nas análises histopatológicas, observou-se redução da inflamação, com ganhos significativos na proliferação celular e maturação tecidual, por comparação ao grupo controle. O carreador SNEDDS por ser um sistema isento de cotensoativo, reforça a proposta da aplicação farmacológica em períodos prolongados, em função da redução do número de ingredientes utilizados no preparo deste sistema carreador e ainda, pelas concentrações encapsuladas dos bioativos de C. cajucara. SNEDDS-OF e SNEDDS-DCTN, por apresentarem ação associada antinociceptiva e antiinflamatória, bem como cicatrizante (SNEDDS-DCTN), poderão atender a uma demanda específica de pacientes que se encontram em tratamentos prolongados (DICs) para combater dor e inflamações causadas por lesões cutâneas ou inflamações crônicas. 2022-06-21T21:00:51Z 2022-06-21T21:00:51Z 2022-02-22 doctoralThesis MEDEIROS, Magnaldo Inácio Tavares. Sistemas coloidais SNEDDS carreadores de Croton cajucara Benth aplicados em modelos experimentais in vivo de antinocicepção, inflamação e cicatrização dérmica. 2022. 176f. Tese (Doutorado em Biotecnologia) - Centro de Tecnologia, Universidade Federal do Rio Grande do Norte, Natal, 2022. https://repositorio.ufrn.br/handle/123456789/48256 pt_BR Acesso Aberto application/pdf Universidade Federal do Rio Grande do Norte Brasil UFRN PROGRAMA DE PÓS-GRADUAÇÃO EM BIOTECNOLOGIA |