Preparation And Targeting Study Of Levofloxacin Loaded Albumin Nanospheres

Nano Drug Delivery Systems refers to the scope of colloidal nano-scale drug delivery system, the general size range 10~1000nm. including nano-liposomes, nanospheres, nano-tank, solid lipid nanoparticles, nano-micelles, nanotechnology milk (microemulsion). nanospheres is natural or synthetic biodegradable and biocompatible polymer is wrapped into drugs, with sustained-release, good stability, security, targeting is of tremendous value.The dissertation can be used with good biocompatibility and biodegradability of albumin as a natural polymer nano-carriers ,Levofloxacin as a model drug, preparation of levofloxacin-albumin nanospheres. Research on the size and distribution of drug nanospheres, and in vitro release evaluation ,and in vivo targeting.PartⅠ: Preparation and Optimization of levofloxacin albumin nano- spheres. We use Sono-chemistry emulsification prepared levofloxacin albumin nanospheres, and determine the best prescription and preparation by the single factor and orthogonal design experiments :levofloxacin 40mg, BSA 800 mg,span- 80 1.4ml,stirring for 30 minutes,ultrasonic vibration 12min,glutaraldehyde 18 ml ,the hardening time of 1.5 hours. According to the best recipe and preparation , we made three batches of samples of the average drug loading and embedding rate of 5.44±0.74% and 82.2±0.40%, showed good reproducibility. Levofloxacin albumin nanospheres is round ball, and measured by the size scope of 50-500nm, nanospheres size mainly concentrated between 200-400nm.Part II: In vitro release study of levofloxacin albumin nanospheres. Oscillation dialysis method used in vitro release. its release (Q=0.0357 t1/2+0. 168, r=0.9942)in vitro was in line with Higuchi equation,indicat -ing levofloxacin albumin nanospheres with a good sustained- release characteristics. Using oscillating dialysis study the different amounts of glutaraldehyde and the different hardening time have impact with the release of the drug nanospheres , glutaraldehyde usage and hardening time have little impact in the release within the scope of the test.PartⅢ: Levofloxacin albumin nanospheres in vivo targeting study. We established the method of HPLC to determine rat tissue concentrations of levofloxacin,levofloxacin concentration in tissue homogenate has a good linear relationship in 0.102- 12.24μg/g, the method recoveries varied from 90% -110% , the extraction recoveries were all higher than 70%, the RSD of within-day and between-day were all less than 6%. After injecting levofloxacin albumin nanospheres solution and levofloxacin solution to rat heart, liver, spleen, lungs,kidneys and lymph,we determinated the tissue concentration of levofloxacin in 1h,6h,12h,24h,48h by HPLC. We use 3p87 pharmacokinetics software for data processing , the relative uptake rate Re 2.477 (P< 0.05) of levofloxacin albumin nanospheres in their lymph , levofloxacin albumin nanospheres showed obvious lymphatic targeting.The dissertation using Sono-chemistry emulsification prepared levofloxacin albumin nanospheres, its average drug loading and embedding rate of 5.44±0.74% and 82.2±0.40%, levofloxacin albumin nanospheres is round ball,and measured by the size scope of 50-500nm, nanospheres size mainly concentrated between 200-400nm,its release in vitro was in line with Higuchi equation , and showed obvious lymphatic targeting.