Influence of formulation parameters on the characteristics of poly(D,L-lactide-co-glycolide) microspheres containing poly(L-lysine) complexed plasmidDNA

This study describes the influence of polymer type, surfactant type/concent ration, and target drug loading on the particle size, plasmid DNA (pDNA) st ructure, drug loading efficiency, in vitro release, and protection from DNa se I degradation of poly(D,L-lactide-co-glycolide) (PLGA) microspheres cont aining poly(L-lysine) (PLL) complexed pDNA. PLGA microspheres containing pD NA-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) e nhanced the stability of pDNA during microsphere preparation. Higher pDNA-P LL loading efficiency (46.2%) and supercoiled structure (64.9%) of pDNA wer e obtained from hydrophobic PLGA (M-w, 31 000) microspheres compared with h ydrophilic PLGA or low-molecular-weight PLGA microspheres. The particle siz e decreased from 6.6 to 2.2 mu m when the concentration of PVA was increase d from 1 to 7%. At the same concentration of surfactant, PVA stabilized mic rospheres showed higher pDNA-PLL loading efficiency (46.2%) than PVP stabil ized microspheres (24.1%). Encapsulated pDNA in PLGA microspheres was prote cted 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-molecu lar-weight PLGA microspheres. The results suggest loading and release of pD NA,-PLL complex can be influenced by surfactant concentration and polymer t ype. (C) 1999 Elsevier Science B.V. All rights reserved.