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1.
J Nutr Biochem ; 131: 109689, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38876393

RESUMO

Females have higher docosahexaenoic acid (DHA) levels than males, proposed to be a result of higher DHA synthesis rates from α-linolenic acid (ALA). However, DHA synthesis rates are reported to be low, and have not been directly compared between sexes. Here, we apply a new compound specific isotope analysis model to determine n-3 PUFA synthesis rates in male and female mice and assess its potential translation to human populations. Male and female C57BL/6N mice were allocated to one of three 12-week dietary interventions with added ALA, eicosapentaenoic acid (EPA) or DHA. The diets included low carbon-13 (δ13C)-n-3 PUFA for four weeks, followed by high δ13C-n-3 PUFA for eight weeks (n=4 per diet, time point, sex). Following the diet switch, blood and tissues were collected at multiple time points, and fatty acid levels and δ13C were determined and fit to one-phase exponential decay modeling. Hepatic DHA synthesis rates were not different (P>.05) between sexes. However, n-3 docosapentaenoic acid (DPAn-3) synthesis from dietary EPA was 66% higher (P<.05) in males compared to females, suggesting higher synthesis downstream of DPAn-3 in females. Estimates of percent conversion of dietary ALA to serum DHA was 0.2%, in line with previous rodent and human estimates, but severely underestimates percent dietary ALA conversion to whole body DHA of 9.5%. Taken together, our data indicates that reports of low human DHA synthesis rates may be inaccurate, with synthesis being much higher than previously believed. Future animal studies and translation of this model to humans are needed for greater understanding of n-3 PUFA synthesis and metabolism, and whether the higher-than-expected ALA-derived DHA can offset dietary DHA recommendations set by health agencies.

2.
Drug Dev Ind Pharm ; 44(12): 2048-2060, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30073852

RESUMO

Different nanoparticles, namely solid lipid nanoparticles, nanocrystals and nanosponges loaded with atorvastatin were successfully fabricated with desirable technological properties which reckoned promising methods of their preparation. Further, suitable characterization and evaluation parameters for in-vitro and in-vivo studies were conducted which led to increase in drug's bioavailability, provided better in-vivo efficacy and reduced toxicity in treating hyperlipidemia systemically. Particle sizes were found to be less than 300 nm with minimal polydispersity indices and maximized entrapment efficiency which are pre-requisites for their absorption in intestines. Drug release studies showed sustained release for a prolonged period, which was justified by release kinetics. Augmented bioavailability and reduced lipoprotein levels were key observations. In addition, reduced hepatotoxicty, decreased myotoxicity and diminished drug distribution were also the important highlights of these developed nanosystems as compared with the pure drug and marketed formulation. Histopathology of liver confirmed reduced hepatotoxicity. An elaborate comparison of these nanoparticles along with pure drug and marketed formulation concluded that nanosponges are potentially one of the best nanosystems for treating hyperlipidemia by systemic delivery.


Assuntos
Anticolesterolemiantes/administração & dosagem , Atorvastatina/administração & dosagem , Portadores de Fármacos/química , Composição de Medicamentos/métodos , Hiperlipidemias/tratamento farmacológico , Nanopartículas/química , Administração Oral , Animais , Anticolesterolemiantes/química , Anticolesterolemiantes/farmacocinética , Atorvastatina/química , Atorvastatina/farmacocinética , Disponibilidade Biológica , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/etiologia , Hiperlipidemias/patologia , Lipídeos/química , Lipoproteínas/sangue , Fígado/efeitos dos fármacos , Fígado/patologia , Ratos , Ratos Wistar
3.
J Drug Target ; 25(8): 685-703, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28521529

RESUMO

High prevalence of topical fungal infections is perceived in majority of nations worldwide accounting for numerous serious systemic complications. Of several fungal infections, candidiasis is one of the widespread infections which is manifested due to localisation and proliferation of fungi. Present pharmacotherapy offers an effective treatment but possesses serious limitations like inadequate solubility, ineffectiveness in lowering diseased condition and patient incompliance. Several attempts to overcome these shortcomings and building suitable technology platforms for development of appropriate dosage forms which can enhance effectiveness, patient acceptability while maintaining safety, efficacy and affordability of drug delivery, have been made. Present review highlights on different types of fungal infections, its aetiology, pathophysiology, epidemiology and conventional formulations used. It also emphasises on applications of several novel approaches of anti-fungal drugs demonstrating advantages and limitations. Details regarding patterns of drug release and its site specificity with better patient compliance have been focussed. Etiology and pathogenesis of candidiasis should be understood clearly. Mentioned novel dosage forms should be explored to enhance therapeutic efficacy, subsequently investigating marketability and patentability. Nanoparticles seem to be a promising approach befitting all requirements.


Assuntos
Antifúngicos/uso terapêutico , Candidíase/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Administração Tópica , Antifúngicos/administração & dosagem , Humanos
4.
J Drug Target ; 24(10): 916-926, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27029893

RESUMO

Emergence of hyperlipidemia in urban population of India and the world at large is very high and accounts to several fatal diseases. This condition is known to manifest elevated levels of lipids and/or lipoproteins. Serious limitations like inadequate solubility, less absorption, less bioavailability, ineffectiveness in lowering of cholesterol levels, patient incompliance and so on are noticed with majority of anti-hyperlipidemic drugs and dosage forms, which are used conventionally. To overcome these shortcomings, building technology platforms for development of appropriate dosage forms is the need of the hour. These efforts are required to maximize patient acceptability while maintaining safety, efficacy, accessibility and affordability. Hyperlipidemia, its types, etiology, pathophysiology and conventional dosage forms are discussed here. The current approaches and novel developments which illustrate controlled drug release and sustained therapeutic effect along with site specific and target oriented drug delivery with better patient compliance are also reviewed critically. Despite the incentives provided by the efforts of formulation scientists, there is still a need for implementation of pharmaceutical technologies that enable to combat limitations of anti-hyperlipidemic drugs and conventional dosage forms associated with it. The present review emphasize on applications of novel drug delivery systems in pharmacotherapy of anti-hyperlipidemic drugs demonstrating the advantages and disadvantages.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/administração & dosagem , Liberação Controlada de Fármacos , Humanos , Hiperlipidemias/metabolismo , Hipolipemiantes/efeitos adversos , Hipolipemiantes/farmacocinética , Hipolipemiantes/uso terapêutico , Lipoproteínas/metabolismo
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