Antiproliferative Activity and VEGF Expression Reduction in MCF7 and PC-3 Cancer Cells by Paclitaxel and Imatinib Co-encapsulation in Folate-Targeted Liposomes.

Co-encapsulation of anticancer drugs paclitaxel and imatinib in nanocarriers is a promising strategy to optimize cancer treatment. Aiming to combine the cytotoxic and antiangiogenic properties of the drugs, a liposome formulation targeted to folate receptor co-encapsulating paclitaxel and imatinib was designed in this work. An efficient method was optimized for the synthesis of the lipid anchor DSPE-PEG(2000)-folic acid (FA). The structure of the obtained product was confirmed by RMN, FT-IR, and ESI-MS techniques. A new analytical method was developed and validated for simultaneous quantification of the drugs by liquid chromatography. Liposomes, composed of phosphatidylcholine, cholesterol, and DSPE-mPEG(2000), were prepared by extrusion. Their surface was modified by post-insertion of DSPE-PEG(2000)-FA. Reaction yield for DSPE-PEG(2000)-FA synthesis was 87%. Liposomes had a mean diameter of 122.85 ± 1.48 nm and polydispersity index of 0.19 ± 0.01. Lyophilized formulations remained stable for 60 days in terms of size and drug loading. FA-targeted liposomes had a higher effect on MCF7 cell viability reduction (p < 0.05) when compared with non-targeted liposomes and free paclitaxel. On PC-3 cells, viability reduction was greater (p < 0.01) when cells were exposed to targeted vesicles co-encapsulating both drugs, compared with the non-targeted formulation. VEGF gene expression was reduced in MCF7 and PC-3 cells (p < 0.0001), with targeted vesicles exhibiting better performance than non-targeted liposomes. Our results demonstrate that multifunctional liposomes associating molecular targeting and multidrug co-encapsulation are an interesting strategy to achieve enhanced internalization and accumulation of drugs in targeted cells, combining multiple antitumor strategies.

Mechanical behaviors of Flutter VRP1, Shaker, and Acapella devices.

BACKGROUND: Flutter VRP1, Shaker, and Acapella are devices that combine positive expiratory pressure (PEP) and oscillations. OBJECTIVES: To compare the mechanical performance of the Flutter VRP1, Shaker, and Acapella devices. METHODS: An experimental platform and a ventilator, used a flow generator at 5, 10, 15, 20, 26, and 32 L/min, were employed at angles of -30°, 0°, and +30° to evaluate Flutter VRP1 and Shaker, whereas Acapella was adjusted at intermediate, higher, and lower levels of resistance, including positive expiratory pressures (PEP) along with air outflow rates and oscillation frequencies. RESULTS: When the relationships between pressure amplitudes of all air flows were analyzed for the 3 devices at low and intermediate pressures levels, no statistically significant differences were observed in mean pressure amplitudes between Flutter VRP1 and Shaker devices. However, both devices had different values from Acapella, with their pressure amplitude values being higher than that of Acapella (P = .04). There were no statistically significant differences in PEP for the 3 angles or marks regarding all air flows. The expected relationships between variables were observed, with increases in PEP, compared to those of air flows and resistance. Nevertheless, there was a statistically significant difference in frequency of oscillation between these devices and Acapella, whose value was higher than those of Flutter VRP1 and Shaker devices (P = .002). At intermediate pressure levels, the patterns were the same, in comparison to low pressures, although the Acapella device showed frequencies of oscillation values lower than those of Flutter VRP1 and Shaker (P < .001). At high pressures, there were no statistically significant differences among the 3 devices for frequency of oscillations. CONCLUSIONS: The Flutter VRP1 and Shaker devices had a similar performance to that of Acapella in many aspects, except for PEP.