Preparation Of Sustained-release BSA/PLGA Microspheres

In recent years,with therapid deverloping of modern biotechnology,genomics,and the combinatorial chemistry,polypeptide and protein drugs had been used in the treatment of human diseases.However,because this kind of drugs had high quality,short half-life,frequent injection dosage,and low bioavailability,studies on the drug delivery system had appealed scholars’ attention.At present,to overcome these questions,biodegradable polymer materials was made into microspheres,and peptides were encapsulated in these microspheres.This method maintained the stability of the drug,got the slow release profile in the body,and finally improved drug bioavailability.In this paper,the coacervation method was used to prepare BSA/PLGA microspheres.We studied the influence factors on microspheres’ preparation,such as the concentration of PLGA,molecular weight of PLGA,Protein protective agent dosage,theoretical drug loadings,the internal phase volume,the dose of coagulant,colostrum ultrasonic process,the condensation process,hardening solvent,hardening temperature,and drying technology.The evaluation indexes were particle size,surface morphology,and drug encapsulation efficiency,etc.Finally,we determined the optimal preparation procedure based on these evaluation indexes.The optimal procedure was shown as followed:(1)PLGA concentration: 80 mg/mL,the theory of drug loadings: 3%,the dosage of sugar: 1.5%,the internal phase volume: 100 μL,and silicone oil consumption: 4 mL;(2)the colostrum ultrasonic technology: the ultrasonic intensity: 300 W,and ultrasonic time: 10 min;(3)the condensation and hardening process: stirring temperature: 15 oC,stirring speed: 500 rpm,and hardening solvent: heptane in 3 oC;(4)drying process parameters: vacuum drying,8 h 3 oC,2 h up to 25 oC,10 h 25 oC.With the optimal process,we fabricated BSA/PLGA microspheres.From the characterization,we could draw a conclusion: microspheres morphology was roundness.The surface had slight fold with uniform dispersion.The average particle size was 100 microns,and the encapsulation efficiency was 85 ± 1.4%.At the same time,this study built fast and effective method to determine accumulated-release amount in dissolution medium.This paper chose accelerated test methods to in vitro study microspheres’ drug release behavior.The release medium was 4-(2-hydroxyethyl)-1-Piperazineethanesulfonic acid(HEPES)buffer.A 30 h test at 50 oC was used to monitor drug release from microspheres.The Micro-BCA method was used to determine drug concentration in release medium.During the release experiments of microspheres,the effect of concentration of PLGA,molecular weight of PLGA,different drug-loading and the DCM: silicone oil to the release behavior were studied.