title: Enhanced encapsulation and bioavailability of breviscapine in PLGA microparticles by nanocrystal and water-soluble polymer template techniques.
abstract: Poly (lactide-co-glycolide) (PLGA) microparticles are widely used for controlled drug delivery. Emulsion methods have been commonly used for preparation of PLGA microparticles, but they usually result in low loading capacity, especially for drugs with poor solubility in organic solvents. In the present study, the nanocrystal technology and a water-soluble polymer template method were used to fabricate nanocrystal-loaded microparticles with improved drug loading and encapsulation efficiency for prolonged delivery of breviscapine. Breviscapine nanocrystals were prepared using a precipitation-ultrasonication method and further loaded into PLGA microparticles by casting in a mold from a water-soluble polymer. The obtained disc-like particles were then characterized and compared with the spherical particles prepared by an emulsion-solvent evaporation method. X-ray powder diffraction (XRPD) and confocal laser scanning microscopy (CLSM) analysis confirmed a highly-dispersed state of breviscapine inside the microparticles. The drug form, loading percentage and fabrication techniques significantly affected the loading capacity and efficiency of breviscapine in PLGA microparticles, and their release performance as well. Drug loading was increased from 2.4% up to 15.3% when both nanocrystal and template methods were applied, and encapsulation efficiency increased from 48.5% to 91.9%. But loading efficiency was reduced as the drug loading was increased. All microparticles showed an initial burst release, and then a slow release period of 28days followed by an erosion-accelerated release phase, which provides a sustained delivery of breviscapine over a month. A relatively stable serum drug level for more than 30days was observed after intramuscular injection of microparticles in rats. Therefore, PLGA microparticles loaded with nanocrystals of poorly soluble drugs provided a promising approach for long-term therapeutic products characterized with preferable in vitro and in vivo performance.
authors.affiliation: Department of Pharmaceutics, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Ningxia Medical University, Yinchuan, Ningxia 750004, China.
authors.forename: Guangxing
authors.initials: G
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Ningxia Medical University, Yinchuan, Ningxia 750004, China; Ningxia Engineering and Technology Research Center for Modernization of Hui Medicine & Key Lab of Hui Ethnic Medicine Modernization, Ministry of Education, Yinchuan, Ningxia 750004, China.
authors.forename: Xueqin
authors.initials: X
authors.lastname: Ma
authors.affiliation: School of Pharmacy, Ningxia Medical University, Yinchuan, Ningxia 750004, China; Ningxia Engineering and Technology Research Center for Modernization of Hui Medicine & Key Lab of Hui Ethnic Medicine Modernization, Ministry of Education, Yinchuan, Ningxia 750004, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Ningxia Medical University, Yinchuan, Ningxia 750004, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Feng
authors.affiliation: Departments of Biomedical Engineering and Pharmaceutics, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Kinam
authors.initials: K
authors.lastname: Park
authors.affiliation: School of Pharmacy, Ningxia Medical University, Yinchuan, Ningxia 750004, China; Ningxia Engineering and Technology Research Center for Modernization of Hui Medicine & Key Lab of Hui Ethnic Medicine Modernization, Ministry of Education, Yinchuan, Ningxia 750004, China. Electronic address: wpwang2015@163.com.
authors.forename: Wenping
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D001682:Biological Availability; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D004655:Emulsions / Q000737:chemistry; D005260:Female; D005419:Flavonoids / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry*; D008863:Microspheres; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D014867:Water / Q000737:chemistry*
chemical_list: D004655:Emulsions; D005419:Flavonoids; D011108:Polymers; D012997:Solvents; D014867:Water; C061097:breviscapine; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Encapsulation efficiency; Nanocrystals; O/W emulsion method; PLGA microparticles; Water-soluble polymer template method