title: Influence of formulation parameters on the characteristics of poly(D, L-lactide-co-glycolide) microspheres containing poly(L-lysine) complexed plasmid DNA.
abstract: This study describes the influence of polymer type, surfactant type/concentration, and target drug loading on the particle size, plasmid DNA (pDNA) structure, drug loading efficiency, in vitro release, and protection from DNase I degradation of poly(D, L-lactide-co-glycolide) (PLGA) microspheres containing poly(L-lysine) (PLL) complexed pDNA. PLGA microspheres containing pDNA-PLL were prepared using the water-in-oil-in-water (w-o-w) technique with poly(vinyl alcohol) (PVA) and poly(vinyl pyrrolidone) (PVP) as surfactants in the external aqueous phase. A complex ratio of 1:0.33 (pDNA-PLL, w/w) enhanced the stability of pDNA during microsphere preparation. Higher pDNA-PLL loading efficiency (46.2%) and supercoiled structure (64.9%) of pDNA were obtained from hydrophobic PLGA (M(w) 31000) microspheres compared with hydrophilic PLGA or low-molecular-weight PLGA microspheres. The particle size decreased from 6.6 to 2.2 microm when the concentration of PVA was increased from 1 to 7%. At the same concentration of surfactant, PVA stabilized microspheres showed higher pDNA-PLL loading efficiency (46.2%) than PVP stabilized microspheres (24.1%). Encapsulated pDNA in PLGA microspheres was protected from enzymatic degradation and maintained in the supercoiled form. The pDNA-PLL microspheres showed in vitro release of 95.9 and 84.9% within 38 days from the low-molecular-weight PLGA and hydrophilic PLGA microspheres, respectively, compared to 54.2% release from the hydrophobic, higher-molecular-weight PLGA microspheres. The results suggest loading and release of pDNA-PLL complex can be influenced by surfactant concentration and polymer type.
authors.affiliation: Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 06100, Ankara, Turkey.
authors.forename: Y
authors.initials: Y
authors.lastname: Capan
authors.forename: B H
authors.initials: BH
authors.lastname: Woo
authors.forename: S
authors.initials: S
authors.lastname: Gebrekidan
authors.forename: S
authors.initials: S
authors.lastname: Ahmed
authors.forename: P P
authors.initials: PP
authors.lastname: DeLuca
mesh_terms: D018736:DNA Adducts / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000737:chemistry*; D003850:Deoxyribonuclease I / Q000737:chemistry; D004587:Electrophoresis, Agar Gel; D019344:Lactic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D010957:Plasmids / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011107:Polylysine / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011142:Polyvinyl Alcohol / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D018736:DNA Adducts; D003692:Delayed-Action Preparations; D011108:Polymers; D013501:Surface-Active Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011107:Polylysine; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011142:Polyvinyl Alcohol; D003850:Deoxyribonuclease I; D011205:Povidone