Multilamellar liposomes of triamcinolone acetonide: preparation, stability, and characterization.

The aim of this study was to assess and characterize the stability of multilamellar liposomes as a delivery vehicle for triamcinolone acetonide. A standardized preparation method for a liposomal delivery vehicle was developed, after varying composition and storage conditions, and assessing encapsulation efficiency and loss of active principle. The assessment of temperature as a factor in formula stability during storage showed that stability improved under refrigeration (4-6 degrees C) (less early diffusion of active principle through the liposomal wall), in comparison with samples stored at room temperature. To improve stability, cholesterol was added to some formulae, which although resulting in a decrease in average encapsulation efficiency, mitigated subsequent losses of retained active principle (formulae 4, 5, and 6), in comparison with those without cholesterol (formulae 1, 2, and 3). This was evident both under refrigerated and room-temperature conditions. Finally, after testing the effects of adding an antioxidant and/or preservative to the formulae, a liposomal design was achieved with acceptable stability, vesicle dimensions, and encapsulation efficiency.

Liposomas de acetónido de triamcinolona: influencia de la composición en el rendimiento y estabilidad / Liposomal triamcinolone acetonide: influence of composition in performance and stability

El acetónido de triamcinolona, antiinfl amatorio esteroideo, presenta por vía tópica los inconvenientes de la corticoterapia. No obstante, su incorporación a un sistema transportador, como los liposomas permitiría prolongar la dosis efectiva en el lugar de acción (dermis y epidermis), reduciendo los efectos secundarios. Así pues, se ha normalizado el método de elaboración de liposomas multilaminares portadores de acetónido de triamcinolona y evaluado el grado de captación del fármaco seleccionado, en función de la composición de los liposomas, determinando los componentes más idóneos para su obtención y los rendimientos proporcionados al variar las concentraciones de los mismos. La adición de colesterol para mejorar su estabilidad, provoca una reducción media en la captación; no obstante la encapsulación sigue siendo bastante elevada. La evaluación de la estabilidad muestra la infl uencia de la temperatura de conservación, de tal manera que los liposomas mantenidos a temperatura de refrigeración (4-6ºC) poseen una estabilidad mayor que las muestras a temperatura ambiente

In topical presentation, Triamcinolone acetonide, a steroidal anti-infl ammatory preparation, presents all the disadvantages of corticotherapy. However, on incorporation into a liposomal drug delivery system, the effectiveness of each dosage within the area of its activity (dermis and epidermis) is prolonged, serving to reduce secondary side effects. For this reason, an attempt has been made to standardize a method for the preparation of a multilaminar liposomal delivery system of triamcinolone acetonide and to assess how much of the drug could be encapsulated by the varying liposomal formulations tested and consequently, which of these would prove to be the most suitable. The addition of cholesterol to such formulations was found to improve stability. However, although such an addition was found to reduce levels of encapsulation of the drug, these still remained suffi ciently high. In the assessment of stability, storage temperature was found to bear an infl uence. Liposomes kept under cold storage (4-6ºC) presented higher stability than samples stored at room temperature

TA1/LAT-1/CD98 light chain and system L activity, but not 4F2/CD98 heavy chain, respond to arginine availability in rat hepatic cells. Loss Of response in tumor cells.

Tumor associated gene-1/L amino acid transporter-1 (TA1/LAT-1) was recently identified as a light chain of the CD98 amino acid transporter and cellular activation marker. Our previous studies with primary rat hepatocyte cultures demonstrated that TA1 RNA levels were responsive to media amino acid concentrations, suggesting adaptive regulation. High level TA1 expression associated with transformed cells also suggested a role in tumor progression. The present study examined the relationship of TA1/CD98 expression, adaptive response, and associated amino acid transport to neoplastic transformation using a panel of well characterized rat hepatic cell lines. We found 1) increased expression of TA1 in response to amino acid depletion, specific for arginine but not glutamine; 2) loss of TA1 response to arginine in gamma-glutamyl transpeptidase-positive transformed and tumorigenic cells; 3) no appreciable response of 4F2/CD98 heavy chain to arginine levels; and 4) correlation of system L amino acid transport activity in response to arginine with changes in TA1/LAT-1 mRNA but not total immunoreacting protein. Our results suggest this CD98 light chain may act as an environmental sensor, responding to amino acid availability and that its regulation is complex. We hypothesize that altered TA1 expression is an early event in hepatocarcinogenesis giving neoplastic cells a growth or survival advantage, particularly under conditions of limited amino acid availability.