Construction Of Ultrasound-stimulated Responsive Mitoxantrone Liposomes

Cancer is one of the most challenging problems in modern medicine.Despite rapid advances in diagnostic procedures and treatments,the overall survival rate from cancer has not improved substantially.Targeted drug delivery system(TDDS)refers to a novel drug delivery system which can deliver a payload accurately to the specified biological targets such as specific cells,tissues,or organs in the desired frequency and duration.The primary goal is to reduce or eliminate unnecessary exposure of non-relevant tissue to the drug in order to improve the efficacy and the tolerability of the treatment.Liposomes as drug cancers have many excellent properties,such as to improve the solubility,bioavailability,stability,targeted delivery,and sustained release.In this study,ultrasound-responsive liposomes(MXT-PLGA-Lip)were prepared by encapsulating mitoxantrone hydrochloride and PLGA nanoparticles,and the feasibility of using ultrasonic stimulation to control drug release was discussed.Ultrasonic therapy apparatus was used to investigate the effect of ultrasound on liposomes drug release.PLGA nanoparticles were used as a key factor to response to ultrasound.Nanoparticles can produce vibrations when stimulated by ultrasound.The vibrations would promote the drug release of liposomes.PLGA-nanoparticles(PLGA-NPs)were prepared by the emulsion solvent extraction/evaporation method using magnetic stirrer and injection syringe.Liposomes were prepared by a lipid film hydration method.MXT was encapsulated into the preformed liposomes using a transmembrane ammonium sulfate gradient-driven loading procedure.Factors influencing entrapment efficiency of liposomes were investigated by single factor,such as concentration of ammonium sulfate in the aqueous phase,the loading time and the loading temperature,the ratio of the drug to the liposome.Then the drug release of liposomes under the conditions of 37 ℃ and ultrasonic stimulation were studied.Liposomes formulation with high stability and strong ultrasonic response were screened.The liposomes were characterized by size,zeta potential,TEM and AFM.We also studied the physicochemical stability of MXT-PLGA-Lip.We systematically examined the response for ultrasound by comparing release characteristics of the liposomes in vitro.MXT-PLGA-Lip demonstrated more sensitive to ultrasonic.The pharmacokinetic characteristics of the prepared liposomes were explored and the effects of ultrasonic stimulation on drug release were studied.The results showed that the MXT-PLGA-Lip had a good sustained-release effect and they could achieve a fast drug release at a mild ultrasonic stimulation.Accordingly,ultrasound-responsive liposomes have a potential application as controlled release drug delivery system.