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Paclitaxel-loaded monodispersed microspheres of narrow size distribution (standard deviation ≤ 1μm) were fabricated using various approaches common to ink-jet technology such as drop-on-demand and continuous mode jetting. The drug-loading efficiency as determined by HPLC was at least 68%. The HPLC analysis showed that the manufacturing process did not affect the drug’s molecule, while the MTT assay on the FaDu carcinoma cells confirmed that the drug retained its pharmacological efficiency. In vitro testing demonstrated that paclitaxel was slowly released from the microspheres for a period of approximate 50 days, with over 80% of the drug being released during this time. Thus, ink-jet technology can be one of the methods of choice for the fabrication of monodispersed microspheres of good pharmacological properties. In contrast to the methods currently described in the literature, it switches the microsphere fabrication procedure from a thermodynamically governed mechanism to a mechano-electrical driven one, hence easier to control./ ]6 ?7 |9 d- E7 E6 Q% \/ w1 F! S
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Films made of 1.5% w/v of the 80/20 copolymer of poly (D,L-lactic acid) and poly-ε-caprolactone dissolved in cellosolve acetate promoted both cell attachment and growing without interfering with the NGF expression capability of these cells. Moreover, the expressed NGF was fully bioactive when this material was used as cell substrate, as confirmed by PC12 cell culture. Thus, the 80/20 PLA/PCL copolymer was a good candidate for being used in conduit manufacturing. The resulting conduits are shown in Figure 8. The layer-by-layer printing process was automated using a repetitive combination of the so-called “layer printing” subroutine and “cleaning” subroutine. The latter performs automatic cleaning the dispensing device after deposition of each layer, preventing possible clogging of the device due to particle contamination or polymer solidification.6 l3 A+ U9 H! q! _# ^
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Programmed target deliveries of 100 μg into spectrophotometric cuvettes gave a standard deviation of dose of 0.6 μg. Jetting on coated, uncut stent tubes exhibited 100% capture efficiency with a 1.8 μg standard deviation for a 137 μg dose. Jetting off-axis to the rotating stent can yield efficiencies up to 91% and CV’s as low as 2%. This is an improvement of greater than 10-fold over the efficiency of conventional spray atomization. Programmed jetting has thus potential for improving the drug loading efficiency which is an important consideration for many of the expensive antiproliferative drugs in use today. |
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