Dry powder inhalation of macromolecules using novel PEG-co-polyester microparticle carriers

This study investigated optimizing the formulation parameters for encapsulation of a model mucinolytic enzyme, alpha-chymotrypsin (alpha-CH), within a novel polymer; poly(ethylene glycol)-co-poly(glycerol adipate-co-omega-pentadecalactone), PEG-co-(PGA-co-PDL) which were then applied to the formulation of DNase I. alpha-CH or DNase I loaded microparticles were prepared via spray drying from double emulsion (w(1)/o/w(2)) utilizing chloroform (CHF) as the organic solvent, L-leucine as a dispersibility enhancer and an internal aqueous phase (w(1)) containing PEG4500 or Pluronic (R) F-68 (PLF68). alpha-CH released from microparticles was investigated for bioactivity using the azocasein assay and the mucinolytic activity was assessed utilizing the degradation of mucin suspension assay. The chemical structure of PEG-co-(PGA-co-PDL) was characterized by H-1 NMR and FT-IR with both analyses confirming PEG incorporated into the polymer backbone, and any unreacted units removed. Optimum formulation alpha-CH-CHF/PLF68, 1% produced the highest bioactivity, enzyme encapsulation (20.08 +/- 3.91%), loading (22.31 +/- 4.34 mu g/mg), FPF (fine particle fraction) (37.63 +/- 0.97%); FPD (fine particle dose) (179.88 +/- 9.43 mu g), MMAD (mass median aerodynamic diameter) (2.95 +/- 1.61 mu m), and the mucinolytic activity was equal to the native non-encapsulated enzyme up to 5 h. DNase I-CHF/PLF68, 1% resulted in enzyme encapsulation (17.44 +/- 3.11%), loading (19.31 +/- 3.27 mu g/mg) and activity (81.9 +/- 2.7%). The results indicate PEG-co-(PGA-co-PDL) can be considered as a potential biodegradable polymer carrier for dry powder inhalation of macromolecules for treatment of local pulmonary diseases. (C) 2012 Elsevier B. V. All rights reserved.