Intratracheal delivery of insulin Absorption from solution and aerosol by rat lung

Okumura, Katsuhiko; Iwakawa, Seigo; Yoshida, Tsuguchika; Seki, Toshimitsu; Komada, Fusao

doi:10.1016/0378-5173(92)90304-k

Cited by 92 publications

(47 citation statements)

References 31 publications

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“…A biodisponibilidade do peptídeo administrado pela rota intratraqueal como solução contendo 1 ou 10 mM de surfactina foi 15,1 e 80,0%, respectivamente. Dados relativos à toxicidade não são apresentados no relato 46 .…”

Section: Figura 1 Estrutura Da Principal Isoforma Da Surfactinaunclassified

“…Relatou-se que a surfactina C, nas concentrações de 3 a 20 μM, aumenta a ativação de pró-uroquinase na presença de plasminogênio (as ativações do plasminogênio e da pró-uroquinase são mecanismos importantes nas etapas de iniciação e propagação da atividade fibrinolítica local) 46 . Isso sugere uma possível aplicação para surfactina em terapia trombolítica.…”

Section: Figura 1 Estrutura Da Principal Isoforma Da Surfactinaunclassified

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Surfactina: propriedades químicas, tecnológicas e funcionais para aplicações em alimentos

Barros¹,

Quadros²,

Júnior³

et al. 2007

Quím. Nova

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Recebido em 11/11/05; aceito em 31/5/06; publicado na web em 19/1/07 SURFACTIN: CHEMICAL, TECHNOLOGICAL AND FUNCTIONAL PROPERTIES FOR FOOD APPLICATIONS. Surfactin, a lipopeptide produced by strains of Bacillus subtilis, has been proved to be a suitable biosurfactant in several applications. For many years, it has been investigated mainly for oil recovery and environmental usage. Its chemical, technological and functional characteristics turn surfactin into an attractive compound for several utilizations. In this review we emphasize some aspects of surfactin as a new food ingredient and its potential pharmaceutical and health applications.Keywords: surfactin; food ingredients; pharmaceutical applications. INTRODUÇÃOSurfactante é uma palavra derivada da contração da expressão "surface active agent", termo que significa, literalmente, agente de atividade superficial. Em outras palavras, surfactante é um composto caracterizado pela capacidade de alterar as propriedades superficiais e interfaciais de um líquido 1,2 . O termo interface denota o limite entre duas fases imiscíveis, enquanto o termo superfície indica que uma das fases é gasosa 1 . Outra propriedade fundamental dos surfactantes é a tendência de formar agregados chamados micelas que, geralmente, se formam a baixas concentrações em água. A concentração mínima na qual se inicia a formação de micelas chama-se concentração micelar crítica (CMC), sendo uma importante característica de um surfactante 1 . Estas propriedades tornam os surfactantes adequados para uma ampla gama de aplicações industriais envolvendo: detergência, emulsificação, lubrificação, capacidade espumante, capacidade molhante, solubilização e dispersão de fases 3 .A produção mundial de surfactantes excede 3 milhões de t/ano sendo que sua utilização se concentra nas indústrias de petróleo, de cosméticos, de produtos de higiene e de limpeza 3 , sendo que este último é o setor que utiliza a maior parte dos surfactantes produzidos como matéria-prima para fabricação de detergentes de uso doméstico 4 .A grande maioria dos surfactantes disponíveis comercialmente é sintetizada a partir de derivados de petróleo. Entretanto, o aumento da preocupação ambiental entre os consumidores, combinado com novas legislações de controle do meio ambiente levou à procura por surfactantes naturais como alternativa aos produtos existentes 4 .Compostos de origem microbiana que exibem atividade superficial são denominados biossurfactantes, consistindo em subprodutos de seus respectivos sistemas metabólicos 5 . Nas últimas décadas, diversos microrganismos têm sido relatados como produtores de vários tipos de surfactantes. A biodegradabilidade 6,7 e baixa toxicidade dos biossurfactantes constituem vantagens adicionais sobre os ingredientes sintéticos e, conseqüentemente, tornam-se substitutos dos emulsificantes convencionais em alimentos e cosméticos 6 , originando maior apelo de mercado pelo fato desses produtos serem considerados naturais, além de apropriados para aplicação ambiental 7 .As bactérias, juntamente com as ar...

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Section: Figura 1 Estrutura Da Principal Isoforma Da Surfactinaunclassified

Surfactina: propriedades químicas, tecnológicas e funcionais para aplicações em alimentos

Barros¹,

Quadros²,

Júnior³

et al. 2007

Quím. Nova

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“…Group 2 received RCRPC of bosentan by intratracheal injection. With the animal secured on its back, the trachea was exposed and then an incision was made between the sixth and fifth trachea rings (Enna & Schanker, 1972;Okumura et al, 1992;Zhang et al, 2001Zhang et al, , 2011Hara et al, 2008). 0.1 mL of RCRPC with 0.1 mL air was injected directly into trachea through a microsyringe with PE tubing (Intramedic Õ PE-50/36'') inserted in the incision.…”

Section: Fine Particle Fraction ðFpfþ Nebulization Efficiency ðNeþ ð2þmentioning

confidence: 99%

Respirable controlled release polymeric colloid (RCRPC) of bosentan for the management of pulmonary hypertension: in vitro aerosolization, histological examination and in vivo pulmonary absorption

2017

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Respirable controlled release polymeric colloid (RCRPC) of bosentan for the management of pulmonary hypertension: invitro aerosolization, histological examination and invivo pulmonary absorption, Drug Delivery, 24:1, 188-198, DOI: 10.1080/10717544.2016 AbstractBosentan is an endothelin receptor antagonist (ERA) prescribed for patients with pulmonary arterial hypertension (PAH). The oral delivery of bosentan possesses several drawbacks such as low bioavailability (about 50%), short duration of action, frequent administration, hepatotoxicity and systemic hypotension. The pulmonary administration would circumvent the presystemic metabolism thus improving the bioavailability and avoids the systemic adverse effects of oral bosentan. However, the short duration of action and the frequent administration are the major drawbacks of inhalation therapy. Thus, the aim of this work is to explore the potential of respirable controlled release polymeric colloid (RCRPC) for effective, safe and sustained pulmonary delivery of bosentan. Central composite design was adopted to study the influence of formulation and process variables on nanoparticles properties. The particle size, polydispersity index (PDI), entrapment efficiency (EE) and in vitro bosentan released were selected as dependent variables. The optimized RCRPC showed particle size of 420 nm, PDI of 0.39, EE of 60.5% and sustained release pattern where only 31.0% was released after 16 h. The in vitro nebulization of RCRPC indicated that PLGA nanoparticles could be incorporated into respirable nebulized droplets better than drug solution. Pharmacokinetics and histopathological examination were determined after intratracheal administration of the developed RCRPC to male albino rats compared to the oral bosentan suspension. Results revealed the great improvement of bioavailability (12.71 folds) and sustained vasodilation effect on the pulmonary blood vessels (more than 12 h). Bosentan-loaded RCRPC administered via the pulmonary route may therefore constitute an advance in the management of PAH.

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“…Among various alternatives, the pulmonary route is the most promising for delivering these drugs, since a number of drugs which are poorly absorbed from enteral and other mucosal sites are well absorbed from the lung due to its large absorptive surface area and the short distance of the air-blood exchange pathway. From these standpoints, absorption experiments have been made on many peptides: insulin, [5][6][7] calcitonin, 8,9) G-CSF, 10) and leuprolide 11) after intrapulmonary administration. We have examined the pulmonary absorption of drugs including peptides and proteins by an in situ pulmonary absorption experiment.…”

mentioning

confidence: 99%

“…We selected insulin in this study, since it has been widely used as a model polypeptide to investigate the absorption characteristics following intrapulmonary administration. [4][5][6] We also examined the effects of various absorption enhancers on the permeability of insulin across this membrane. Furthermore, we described the effects of these enhancers on the electrophysiological parameters of Xenopus pulmonary membrane to clarify their absorption enhancing mechanisms.…”

mentioning

confidence: 99%

Evaluation of Insulin Permeability and Effects of Absorption Enhancers on Its Permeability by an in Vitro Pulmonary Epithelial System Using Xenopus Pulmonary Membrane.

Yamamoto

Tanaka

Okumura

et al. 2001

Biological & Pharmaceutical Bulletin

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The permeability of insulin across Xenopus pulmonary membrane and the effects of various absorption enhancers on insulin permeability were examined using an in vitro Ussing chamber technique. Absorption enhancers used in this study were sodium caprate (NaCap), sodium glycocholate (NaGC), sodium salicylate (NaSal) and ethylenediaminetetraacetic acid disodium salt (EDTA). The permeability of insulin across Xenopus pulmonary membrane significantly increased in the presence of NaCap and NaGC, while EDTA and NaSal did not enhance the permeability. In addition, the enhancing effect of NaGC increased as the concentrations of these enhancers increased. Transmembrane resistance (Rm) of Xenopus lung was markedly decreased in the presence of these enhancers, and NaCap showed a greater effect on Rm than NaGC. Furthermore, the amount of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) released from the apical side of the Xenopus pulmonary membrane increased in the presence of these enhancers. These results indicate that NaCap and NaGC improve the pulmonary absorption of insulin, but they are toxic to the pulmonary membrane. These findings suggest that this method is useful for estimating the permeability characteristics of peptides across the pulmonary membrane and for evaluating the effects of various additives on their permeability and their membrane toxicity.

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Intratracheal delivery of insulin Absorption from solution and aerosol by rat lung

Cited by 92 publications

References 31 publications

Surfactina: propriedades químicas, tecnológicas e funcionais para aplicações em alimentos

Surfactina: propriedades químicas, tecnológicas e funcionais para aplicações em alimentos

Respirable controlled release polymeric colloid (RCRPC) of bosentan for the management of pulmonary hypertension: in vitro aerosolization, histological examination and in vivo pulmonary absorption

Evaluation of Insulin Permeability and Effects of Absorption Enhancers on Its Permeability by an in Vitro Pulmonary Epithelial System Using Xenopus Pulmonary Membrane.

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