Preliminary Study On Fibrauretin Nanoparticles

The fibrauretin has many pharmacological actions of antibacterium, antiplasmodium, antifungus,antivirus and so on, but the biological availability is low (about 10%) because of small dissolvability in water and first pass effect of liver. in this research taking advantages of the nanoparticles such as increasing the drug dissolvability, protectiving drug to avoid the degradationsof liver drug enzyme and prolonging the blood circulation time, the uptake amount of fibrauretin is increased by organism, or the traditional fibrauretin preprations was recasted by using the polybutylcyanoacrylate as the carrier. At first, the establishment of the ultraviolet analytical method, the preparation condition was initially selected by the single fact test, meanwhile the process was optimized by the orthogonal design test with the factors which influencing nanoparticles quality as the investigation standard, then the quality, the security, the pharmacodynamics and the release properties in vitro were initially studied. The abstracts are as follows:1.The establishment of the ultraviolet analytical method on fibrauretin.To establish the ultraviolet analytical method on fibrauretin for content determining of fibrauretin preparations and study need of the release properties in vitro. The ultraviolet absorption wavelength, the standard curve, the recovery and accuracy were studied by the ultraviolet spectrophotometer. Results showed that the fibrauretin has the maximal absorption in 273.5nm, the good linear range was from 5μg/ml to 25μg/ml, and the mean recovery is 99.58%, the RSD of repeatability is 2.7%, the accuracies with-day and between-day are not morn than 1%. The analytical method have many merits of operation convenient, tabilization reliability and high reproducibility. It can meet the need of preparation and study on fibrauretin nanoparticles.2.The preparation and quality evaluation of polybutylcyanoacrylate nanoparticles loaded with the fibrauretin(F-PBCA-NP). The F-PBCA-NP was manufactured by the emulsion polymerization, then the quality was evaluated. With the morphology, particle size,the drug loading and the embedding ratio of these nanoparticles as the investigation standard, the surfactant, PH, temperature, stirring speed, supplement and procedure was decided by the single factor test, The process was optimized by the L9(34) orthogonal design test with the consideration of the factors influencing nanoparticles quality which included the fibrauretin concentration(A), the butylcyanoacrylate dosage(B), the Dextran-70+PluronicF-68 amount(C). the physico-chemical characters were detected by electron microscope, the photon correlation spectroscope and ultracentrifugation on low temperature. Results showed that the fibrauretin nanoparticles made with Dextran-70+PluronicF-68 (1:1) as the surfactant, PH 2.5, temperature 25℃,stirring speed800r/min, supplement Na2S2O5 and one procedure;fibrauretin1.5mg/ml,BCA 2.0mg/ml, Dextran-70+Pluronic F-68 (1:1) 4.0mg/ml were sphere like , the even diameter was (72±5)nm,the drug loading was 50.9%, and the embedding ratio was 67.8%. It is concluded that the preparation method is stable and feasible, It conforms to the request of preparation.3.The acute toxicity experiment of the F-PBCA-NP on mice.To know the acute toxicity of the fibrauretin nanoparticles on mice.The mice were given multiplely with the fibrauretin preparations including watersolution and nanoparticles through the intragastric administration. The acute toxic reaction of mice was observed, and the death number was reported, the maximal tolerance dose (MTD),the LD50 and the LD50 95% confidence limit of the fibrauretin nanoparticle was calculated.Results showed the MTD on mice of the fibrauretin nanoparticles was 4.7 times than its watersolution;the LD50 of the fibrauretin nanoparticles is 1706.85mg/kg. So the fibrauretin nanoparticles is nontoxic and conform to the request of clinical medication.4. The antibacterial action in vivo and anti-infection experiment of the F-PBCA-NP. The antibacterial action in vivo and anti-infection effect of fibrauretin nanoparticles was evaluated. The antibacterial action in vitro of the F-PBCA-NP was investigated with S.aureas and E.coli as the objects; the anti-infection effect of thats was viewed with mice infected by S. aureas as the experimental animals, the survival rates of mice, weight changs and extent of pathological changes of important organs as judgement standard, compared with other preparation.Results showed that the bacteriostasis circle diameter of these preparations on these two genuis exceeded 10mm, the antibacterial action of the F-PBCA-NP was increased, compared with others; the F-PBCA-NP was 80% in the survival rates of mice infected by S.aureas, but the ordinary preparations 35%, had more improvements on spleen weight index and pathological changes than ones. So the antibacterial action of the fibrauretin nanoparticles is better than the tablet and capsule.5.The release properties in vitro of the F-PBCA-NP.The release properties in vitro of the fibrauretin nanoparticles were studied.compared with the fibrauretin tablet and capsule, the release pattern of the F-PBCA-NP was investigated by the dialytic. The cumulated releasing curve wered drawed,the six release model carve were used to fitting the release curve. Results showed that the release pattern was characterized by two phases kinetics, in the accordence with Weibull's equation: y=0.3569x-0.2201. It is concluded that the fibrauretin nanoparticles shows significant sustained release.