Poly(Glycerol Adipate-co-ω-Pentadecalactone) Spray-Dried Microparticles as Sustained Release Carriers for Pulmonary Delivery

The aim of this work was to optimize biodegradable polyester poly(glycerol adipate-co-omega-pentadecalactone), PGA-co-PDL, microparticles as sustained release (SR) carriers for pulmonary drug delivery. Microparticles were produced by spray drying directly from double emulsion with and without dispersibility enhancers ((L)-arginine and (L)-leucine) (0.5-1.5%w/w) using sodium fluorescein (SF) as a model hydrophilic drug. Spray-dried microparticles without dispersibility enhancers exhibited aggregated powders leading to low fine particle fraction (%FPF) (28.79 +/- 3.24), fine particle dose (FPD) (14.42 +/- 1.57 mu g), with a mass median aerodynamic diameter (MMAD) 2.86 +/- 0.24 mu m. However, (L)-leucine was significantly superior in enhancing the aerosolization performance ((L-)arginine:%FPF 27.61 +/- 4.49-26.57 +/- 1.85; FPD 12.40 +/- 0.99-19.54 +/- 0.16 mu g and MMAD 2.18 +/- 0.35-2.98 +/- 0.25 mu m, (L)-leucine:%FPF 36.90 +/- 3.6-43.38 +/- 5.6; FPD 18.66 +/- 2.90-21.58 +/- 2.46 mu g and MMAD 2.55 +/- 0.03-3.68 +/- 0.12 mu m). Incorporating (L)-leucine (1.5%w/w) reduced the burst release (24.04 +/- 3.87%) of SF compared to unmodified formulations (41.87 +/- 2.46%), with both undergoing a square root of time (Higuchi's pattern) dependent release. Comparing the toxicity profiles of PGA-co-PDL with (L)-leucine (1.5%w/w) (5 mg/ml) and poly(lactide-co-glycolide), (5 mg/ml) spray-dried microparticles in human bronchial epithelial 16HBE14o- cell lines, resulted in cell viability of 85.57 +/- 5.44 and 60.66 +/- 6.75%, respectively, after 72 h treatment. The above data suggest that PGA-co-PDL may be a useful polymer for preparing SR microparticle carriers, together with dispersibility enhancers, for pulmonary delivery.