| A new type of magnetic nanoparticles drug system is one of the highlights in the biomedical field.Cystic fibrosis(CF)is caused by a frameshift mutation in the gene with a very high fatality rate.The main symptoms of CF is thick mucus grow out of control which may decrease the effective drugs reaching the lesions and shorten the residence time of drug.Finally,it will lead the failure of treatment.Here,we design two kinds of Tobramycin sulfate(TOB)/MAG-CMX(Magnetic nanoparticles-Carboxymethyldextran)sustained and controlled release delivery system.The objective of this study was to control the drug release rate and release time through changing release condition and to improve the therapeutic effect of cystic fibrosis.We have achieved a series of attractive results as follow:1.Successfully prepare TOB/MAG-CMX sustained and controlled release delivery system,characterize the products and optimize the preparation condition.TOB were conjugated via their amine groups,to the carboxylic functional groups coating the magnetic nanoparticles MAG-CMX.FTIR and confocal microscopy were used to characterize the conjugation products.Drug loading capacity of TOB was determined by LC-MS/MS,52.5%.The optimized condition was as below:rate of EDC and sulfo-NHS was 2:1;pH value of MES buffer was 4.5;activation time of Carboxyl in MAG-CMX was 6 hours.The particles size distribution of TOB/MAG-CMX was 110-490nm,with a poly dispersity index(PDI)less than one.It is indicated that drug conjugation did not induce any signficant aggregation of magnetic nanoparticles2.We investigated the release profile of TOB/MAG-CMX sustained and controlled release delivery system.Drug release studies were performed in simulated physiologic conditions using crude protease dissolved in PBS buffer and oscillating magnetic field(OMF).It can keep sustained release for 72 hours in crude protease.15%of total TOB was released from the conjugates after incubation for 72 hours or more.In addition,magnetically triggered release studies were performed using an external OMF.Total 15%TOB was released from conjugates after 6 hours in OMF.A pulsatile release study was also conducted where the OMF was turned on and off.In"OFF" period,release rate was less than 1%,while the accumulation release percentage was 13.5%in total 3 "ON" period.This study confirmed the ability to control drug release using this externally triggered system.3.Successfully prepare TOB encapsulated PLGA magnetic sustained and controlled release delivery system,characterize the products and optimize the preparation condition.We prepared TOB encapsulated in PLGA magnetic micro/nanoparticles by solvent evaporation method and optimize the prepare condition as below:TOB/PLGA.MAG-CMX nanoparticles:2%PVA;first emulsification amplitude 40%;emulsification speed 15000rpm;TOB/PLGA/MAG-CMX microparticles:2%PVA;first emulsification amplitude 40%;second emulsification amplitude 40%.Characterize using SEM,DLS and so on.According to the result of SEM,both nano and microparticles were spherical in morphology with relatively smooth surfaces.The particle size of nanoparticles was 220.9±7.4nm,and it was 1.45±0.74?m of microparticles.Loading efficiencies were 57.4%of nanoparticle,and 82.6%of microparticle.4.We investigated release profiles of TOB encapsulated PLGA magnetic sustained and controlled release delivery system in different condition.Normal and triggered release properties based on their different encapsulation structure were studied.In passive in-vitro release studies,TOB encapsulated in PLGA resulted in a continuous drug release.It showed a sustained release manner in PBS buffer for 30 days.When exposed to an OMF,total 22.3%TOB from nanoparticles and 23.5%TOB from microparticles were released in 6 hours.A magnetic field turn-on and-off experiment was also conducted to confirm the control of drug release using this triggered system.The release rate in "OFF" period was less than 4?g/hour,while it increased to 50?g/hour in the "ON" period.5.Anti-bacteria activities of drug released from TOB/MAG-CMX,TOB encapsulated PLGA magnetic sustained and controlled were tested.In bioactivity study,pseudomonas aeruginosa biofim was used to investigate the inhibition of TOB.The inhibition rates of 1?g/mL TOB released from TOB/MAG-CMX in protease and under OMF were about 37%compared to 38,4%of standard TOB solution.While the inhibition rates range was 20%-34%for TOB/PLGA/MAG-CMX delivery system in PBS buffer and under OMF.TOB maintained its antimicrobial activity after conjugation,encapsulation and triggered release,indicating that these delivery system has potential value in the area of biomedicine... |
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