Study On Moxifloxacin Liposome Gel For Lung Targeting Drug Delivery System

[Object] Establish suitable for interventional treatment of lung via fiberoptic bronchoscopy slow-release drug carrier, aimed at improving the stay of drugs in the lungs, realize slow and sustained release drugs, in order to reduce dosing frequency and improve patient compliance, improve the clinical cure rate.This study with MXF as model drug, MXF liposome prepared by ammonium sulphate gradient method, then hyaluronic acid as gel carrier, MXF liposome gel compound preparation is suitable for the interventional treatment of lung by bronchoscopy, and the preparation technology、representation、the slow-release in vitro, the safety of animal lungs application and pharmacokinetic of drug-containing liposome and medicated liposome gel are evaluated and investigated.[Method] This paper applied high performance liquid chromatography to establish analysis method of MXF; This research adopts the ammonium sulfate gradient method combined with high pressure homogeneous to prepare the liposome of MXF, with particle size and its distribution and the envelopment rate, drug loading as examining index, optimize the prescription and process, determine the best preparation technology. Put MXF liposome at37℃for two months to investigate the changes of the entrapment efficiency and particle size. Testing that liposome gel compound preparation whether can sweep through the catheter, to determine the HA dosage; The release of MXF from liposome and liposome gel in vitro was studied by dynamic dialysis method and HPLC; New Zealand white rabbits and beagle as models for general observation and a certain time of lung tissue pathological observation to make a preliminary evaluation for MXF liposome gel compound preparation application feasibility and safety of the lungs. For single lung dose in the healthy New Zealand white rabbit give MXF liposome gel compound preparation, blood drug concentration and drug concentration in lung tissue were determined by HPLC. The pharmacokinetic parameters were acquired with DAS2.0software and analyzed using SPSS19.0statistic software.[Results] The best preparation process:ammonium sulfate concentration of70mg/m L, phospholipids mass concentration of50mg/m L, size of blank liposome about120 nm, dialysis time5h, medicine fat than2:3, incubation temperature40℃, the incubation time30min; According to the optimal formulation, the entrapment efficiency, the drug loading and the average diameter of the prepared liposome were (74.56+3.21)%,(25.96+1.11)%and (143±3.98) nm respectively. The entrapment efficiency and average diameter had no significant difference after stored at25℃for two months; When HA concentration was1.75%, the preparation can pass catheter, both have good needle, and can improve the adhesive force and extend the retention time of drug preparation in the lesions; The release behavior of MXF liposome and liposome gel compound preparation in vitro is basic unanimously, release is divided into three stages, at the beginning of the release MXF released about25%(basically from free MXF), in24hours freed up about60%of the quantity, next the release enter the platform period; MXF liposome gel compound preparation can be absorbed in lungs,will not affect the normal breathing function of experimental animals, are nonirritant for bronchial mucosa and won’t cause lung tissue pathological change, the feasibility and safety are preliminary established. For MXF liposome gel, the blood drug concentration up to peak around4h, peak value of1.48μg/ml. Blood drug concentration after24h down to0.2μg/ml, t1/2β is28.6h. Local drug concentration in lung tissue reduce obviously slow, t1/2β is32.3h, after injection144h the drug concentration remain more than0.25ug/ml (minimal inhibitory concentrations).[Conclusion] MXF liposome prepared with the ammonium sulfate gradient combine with high pressure homogeneous method, particle size distribution is narrow, the encapsulation rate is high, slow-release character and stability are good, and significantly alter the pharmacokinetic behavior of MXF, make it release slowly and remove slowing down. Liposome gel compound preparation has biological safety, at the same time, adopt the lung intervention can improve the drug content in the lung tissue, extend the lung residence time, improve the effectiveness.