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Influence of formulation parameters on the characteristics of poly(d,l-lactide-co-glycolide) microspheres containing poly(l-lysine) complexed plasmid DNA

1999; Elsevier BV; Volume: 60; Issue: 2-3 Linguagem: Inglês

10.1016/s0168-3659(99)00076-0

1873-4995

Yılmaz Çapan, Byung Ho Woo, Sisay Gebrekidan, Shamim Ahmed, Patrick P. DeLuca,

Biopolymer Synthesis and Applications

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 (Mw 31 000) microspheres compared with hydrophilic PLGA or low-molecular-weight PLGA microspheres. The particle size decreased from 6.6 to 2.2 μm 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.