title: Stability and release characteristics of poly(D,L-lactide-co-glycolide) encapsulated CaPi-DNA coprecipitation.
abstract: The aims of this work were to determine the stability of DNA-calcium-phosphate coprecipitation (CaPi-DNA) against various conditions during double emulsification microencapsulation and assess the release and physicochemical characteristics of poly(D,L-lactide-co-glycolide) (PLGA) microparticles loading CaPi-DNA. CaPi-DNA prepared at pH 6.5 showed a good stability with over 60% CaPi-DNA remained after emulsification, but no more than 40% at pH 8.0. Polyvinyl alcohol (PVA, 1-5%) could make over 80% CaPi-DNA (pH 7.0) preserved after homogenization. The dichloromethane (DCM), mixture of DCM and ethyl acetate, ether and n-hexane (1:1) exhibited neglectable influence on CaPi-DNA under homogenization. PLGA had influenced on CaPi-DNA without any additional stabilizer, in particular, PLGA (75:25, 4%, w/v) demonstrated a profound damage with only about 10% of the original CaPi-DNA remained. PLGA microparticles loading CaPi-DNA were spherical in shape with size range of 2.0-5.0microm, and entrapment efficiency 30-50%. CaPi-DNA was found to increase the stability of pDNA in PLGA microparticles without losing its structure integrity. The release of CaPi-DNA from microparticles showed a low burst release (<7.5%) within 24h and following sustained release process. The amount of cumulated CaPi-DNA release over 30 days was: 17.6% for PLGA (lactide:glycolide=50:50), 27.3% for PLGA (65:35) and 44.8% for PLGA (75:25) microparticles, respectively. The encapsulation of CaPi-DNA in microparticles could significantly protect CaPi-DNA from degradation of nuclease with average over 80% of total DNA recovery. These results suggested that the encapsulation of CaPi-DNA in PLGA microparticles could improve stability of pDNA.
authors.affiliation: Center of Drug Research, Department of Pharmacy, Ludwig-Maximilians-University, Butenandtstrasse 5-13, D-81377 Munich, Germany. ypli@mail.shcnc.ac.cn
authors.forename: Yaping
authors.initials: Y
authors.lastname: Li
authors.forename: Manfred
authors.initials: M
authors.lastname: Ogris
authors.forename: Jaroslave
authors.initials: J
authors.lastname: Pelisek
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Röedl
mesh_terms: D002130:Calcium Phosphates / Q000737:chemistry*; D002214:Capsules; D011232:Chemical Precipitation; D004247:DNA / Q000737:chemistry*; D003850:Deoxyribonuclease I / Q000737:chemistry; D004339:Drug Compounding; D004355:Drug Stability; D004587:Electrophoresis, Agar Gel; D004655:Emulsions; D006016:Glycolates / Q000737:chemistry*; D019344:Lactic Acid; D008855:Microscopy, Electron, Scanning; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013997:Time Factors
chemical_list: D002130:Calcium Phosphates; D002214:Capsules; D004655:Emulsions; D006016:Glycolates; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C485838:calcium phosphate, monobasic, anhydrous; D004247:DNA; C020243:calcium phosphate; D003850:Deoxyribonuclease I; C485829:calcium phosphate, dibasic, anhydrous