Potential applications of PLGA film-implants in modulating in vitro drugs release.
ABSTRACT In this work we evaluate poly(lactic/glycolic) acid (PLGA) film-implants as potential biodegradable devices for controlled release of two different drugs: 5-Fluorouridine (5-FUR), a conventional low molecular weight water-soluble compound and SPf66 malaria vaccine, a therapeutic synthetic polypeptide. Three types of devices were prepared by solvent-casting techniques alone or combined with compression method: simple monolithic discs (SMD), multilayer discs with a central monolithic layer (MLDM), and multilayer discs with a central drug-reservoir (MLDR). For the highly water-soluble drug, 5-FUR, in vitro release from SMD showed an initial burst (24% in 2 h) followed by prolonged release over 20 days. In contrast, from a MLDM (two drug-free PLGA discs were added to the SMD) showed an initial lag-time of 12 days followed by a very fast second release phase. Finally, when the load of this system was increased from 3 to 9%, an extended release over 20 days with a low burst effect was obtained. For SPf66, the central reservoir containing the synthetic polypeptide MLDR reduces the possibility of degradation due to peptide contact with polymer solution. When four layers were added, 10 days sustained-release was obtained without any burst effect. With six layers a moderate pulse was obtained, 18-22 days from the beginning of the release. The results show the suitability of the proposed devices to control release and avoid the burst effect with highly water-soluble drugs; as well as modulate in vitro peptide release.
- Journal of Metamorphic Geology - J METAMORPH GEOL. 01/1988; 6(4):475-494.
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ABSTRACT: The slopes of the liquidus and lines of constant liquid-vapor homogenization temperature (iso-Th) in P - T space for a 40 wt% NaCl bulk composition in the H 2 O-NaCl system were determined using synthetic fluid inclusions. Inclusions were synthesized in the one-phase field at 350°-800°C and 1-6 kbar, and the temperatures of liquid-vapor homogenization and halite dissolution were determined on a heating/cooling stage. The pressure along the liquidus corresponding to a measured halite dissolution temperature [Tm (halite)] was determined from the intersection of the inclusion iso-Th line in the one-phase field with the measured Tm (halite). The P - T position of the iso-Th line in the one-phase field was determined from the measured liquid-vapor homogenization temperature [Th ( L - V )] of a given inclusion and the known experimental formation temperature and pressure for that same inclusion. The slope of the 40 wt% halite liquidus determined from synthetic fluid inclusions is -5.5°C/kbar. This value is in good agreement with an extrapolation of the data of et al. (1983) and cooling data of (1991) to lower salinities, but shows considerable disagreement with the extrapolated heating data of (1991). Over the salinity range 27-100 wt% NaCl, the slope of the halite liquidus predicted by the results from this study combined with data of (1978), et al. (1983), and cooling data of (1991) is given by dT / dP (° C / kbar ) = - 38.38 + 0.90 S - 0.0029 S 2 , where " S " is the salinity in wt% NaCl. Microthermometric data combined with the known temperatures and pressures of formation were used to construct lines of constant liquid-vapor homogenization temperature (iso-Th) for fluid inclusions with a salinity of 40 wt% NaCl. The slopes of the iso-Th lines for inclusions which homogenize by vapor-bubble disappearance decrease smoothly with increasing Th, from 14.1 bars/°C for inclusions which homogenize at 323°C to 5.52 bars/°C for inclusions with homogenization temperatures of 650°C. For inclusions which homogenize by halite dissolution (Th < 323°C), the slopes of the iso-Th lines within the one-phase liquid field decrease with increasing Th ( L - V ) from 21.5 bars/°C (150°C) to 14.1 bars/ °C (323°C). The average slopes of the iso-Th lines within the liquid + halite field are much steeper than those in the one phase field, and decrease from 24.8 bars/°C at 150°C to 20.3 bars/°C at 300°C.Geochimica et Cosmochimica Acta 01/1994; 58:1053-1063. · 3.88 Impact Factor
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ABSTRACT: The geochemical features of fluids accompanying the first stages of geothermal activity linked to magmatic intrusions have been documented for the Larderello geothermal system (Italy). Deep drilling has provided samples which preserve evidence of this early geothermal activity. Four wells (San Pompeo 2, Monteverdi 7, Sasso 22, and Serrazzano, VC 11) penetrated the deeper parts of the Larderello system, located in a metamorphic basement underlying the Tertiary nappe complex which constitutes the main aquifer at Larderello. The drill holes terminated close to the inferred roof of a granitic complex thought to be responsible for geothermal activity.Fluid inclusion data were obtained from recrystallized quartz lenses and quartz veins in samples displaying high temperature assemblages (plagioclase-actinolite-biotite-tourmaline; clinopyroxene ± andradite-wollastonite) and also from magmatic quartz in a leucogranite dike. The inclusions are mainly secondary in origin, oriented in fluid inclusion planes (FIP) related to hydrothermal circulation in the Larderello system. Several generations of high temperature fluids were trapped and include: 1.(1) H2OCO2 dominated vapors displaying variable but significant contents of CH4 and N2;2.(2) aqueous vapors containing LiCl, with variable salinity;3.(3) aqueous LiCl brine, often oversaturated with respect to halite at room temperature;4.(4) complex brine, always oversaturated at room temperature with respect to two (halite and sylvite) or more (n ≤ 4) salts. The presence of LiCl was confirmed by identification of the salt hydrate (LiCl5H2O) at very low temperature using Raman spectroscopy. Bulk salinities could be roughly estimated at around 30 wt% eq. LiCl for the LiCl brine.Geometric and chronologic relationships between FIP reveal close relationships and mutual contamination between the H2OCO2 vapors and LiCl brine, indicating synchronism in their trapping. These fluids were generated and trapped at pressures of 100–130 MPa, nearly 23 MPa above the estimated present-day lithostatic pressure. This implies a denudation rate between 0.2 and 0.5 mrn· a−1 since the onset of hydrothermal activity, compatible with the setting of Larderello in a young (Tortonian) collision belt. Fluid inclusion trapping temperatures (425–650°C) show a monotonous increase towards the inferred granite, and are around 100–200°C higher than the highest present-day temperatures.The results are interpreted as recording the interaction between magmatic and contact metamorphic fluids in the early Larderello system. The H2OCO2 vapors resulted from the reheating of the basement metamorphic series (often C-rich) under relatively high temperatures during contact metamorphism. Lirich fluids expelled from an underlying Li-rich leucogranite migrated through the metamorphic series and the already cooled granite dikes and experienced local boiling. The fluid inclusion data demonstrate the involvement of magmatic fluids during the initial development of this high energy geothermal field.Geochimica et Cosmochimica Acta 01/1994; 58(3):1083-1099. · 3.88 Impact Factor