RESUMO
BACKGROUND: Successful delivery of anticancer drugs to intracellular targets requires different properties of the nanocarrier to overcome multiple transport barriers. However, few nanocarrier systems, to date, possess such properties, despite knowledge about the biological fate of inorganic and polymeric nanocarriers in relation to their fixed size, shape and surface properties. Herein, a polymer-lipid hybrid nanoparticle (PLN) system is described with size and shape transformability and its mechanisms of cellular uptake and intracellular trafficking are studied. METHODS: Pharmaceutical lipids were screened for use in transformable PLN. Mechanisms of cellular uptake and the role of fatty acid-binding proteins in intracellular trafficking of PLN were investigated in breast cancer cells. Intra-tumoral penetration and retention of doxorubicin (DOX) were evaluated by confocal microscopy. RESULTS: The lead PLNs showed time-dependent size reduction and shape change from spherical to spiky shape. This transformability of PLNs and lipid trafficking pathways facilitated intracellular transport of DOX-loaded PLN (DOX-PLN) into mitochondria and nuclei. DOX-PLN significantly increased DOX penetration and retention over free DOX or non-transformable liposomal DOX particles at 4 h post-intravenous administration. CONCLUSION: Transformability of PLN and lipid-biology interplay can be exploited to design new nanocarriers for effective drug delivery to tumor cells and intracellular targets.
Assuntos
Antineoplásicos , Nanopartículas , Nanoestruturas , Antineoplásicos/farmacologia , Biologia , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Portadores de Fármacos , Humanos , Lipídeos , PolímerosRESUMO
The objective of this review is to discuss the effect of white vegetable consumption on glycemia, satiety, and food intake. White vegetables is a term used to refer to vegetables that are white or near white in color and include potatoes, cauliflowers, turnips, onions, parsnips, white corn, kohlrabi, and mushrooms (technically fungi but generally considered a vegetable). They vary greatly in their contribution to the energy and nutrient content of the diet and glycemia and satiety. As with other foods, the glycemic effect of many white vegetables has been measured. The results illustrate that interpretation of the semiquantitative comparative ratings of white vegetables as derived by the glycemic index must be context dependent. As illustrated by using the potato as an example, the glycemic index of white vegetables can be misleading if not interpreted in the context of the overall contribution that the white vegetable makes to the carbohydrate and nutrient composition of the diet and their functionality in satiety and metabolic control within usual meals. It is concluded that application of the glycemic index in isolation to judge the role of white vegetables in the diet and, specifically in the case of potato as consumed in ad libitum meals, has led to premature and possibly counterproductive dietary guidance.