Pireparration Of Paclitaxel Loaded Nanoparticles(np)in Microchannels And Study On The Pharmacodynahtmics

Paclitaxel is widely used to treat several types of solid tumors,but its application on clinic was significantly limited due to side-effects associated with solubilizer used in its commercial formulation and the tendency of the drug to precipitate in aqueous media.In this study,a rectangular microchannel with cross and T-shaped junctions was fabricated successfully on a stainless steel slab by the mechanical micro-cutting method.Paclitaxel was encapsulated in poly(D,L-lactide-co-glycolide)nanoparticles(PTX-NPs)by rectangular microchannels.Main contents and results are as follows.The mechanical micro-cutting method was employed to manufacture microchannels with regular shapes and precise sizes,which are easy to be scaled-up.A rectangular microchannel with cross and T-shaped junctions was fabricated successfully on a stainless steel slab by the mechanical micro-cutting method.The microchannels was assembled and adjusted before using.A precise and convenient HPLC method was established to determine the concentration of paclitaxel.The characteristic of linearity,accyracy and precision was investigated with this method.Paclitaxel nanoparticles(PTX-NPs)was prepared by rectangular microchannels method.The influence of aqueous phase flow and concentration of aqueous phase,lipid phase flow and concentration of lipid phase flow,gas phase flow were investigated by single factor experiment.Orthogonal design was utilized to optimize prescription.PTX-NPs were prepared with optimized prescription demonstrated good stability.The encapsulation efficiency and drug loading of PTX-NPs were(43.67±0.55)%and(3.11±1.9)%respectively,the average size was(129.73±2.41)nm and the Zeta potential was-(24.02±0.36)mV.Differential scanning calorimetry(DSC)and transmission electron microscope(TEM)were used to analyze the existence state of the paclitaxel in NPs and morphology of PTX-NPs respectively.The in vitro release behavior exhibited that paclitaxel released from PTX-NPs over 120 hours with initial burst release and,later,sustained release.The amount of cumulated paclitaxel release in 120 hours was 87.3%.In vitro antitumor activity of the PTX-NPs against rat breast cancer MCF-7 cells was evaluated by MTT method.The results showed that in comparison with paclitaxel the minimal inhibitory concentration of PTX-NPs is remarkably lower.The pharmacokinetics study was carried out in rats.In compare with injective solution,PTX-NPs showed a remarkable sustained release.In conclusions,preparation NPs in rectangular microchannels is a feasible novel method and the Paclitaxel-NPs seem to be a promising alternative formulation for injectable paclitaxel administration.