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, α-chymotrypsin (α-CH), within a novel polymer; poly(ethylene glycol)-co-poly(glycerol adipate-co-ω-pentadecalactone), PEG-co-(PGA-co-PDL) which were then applied to the formulation of DNase I. α-CH or DNase I loaded microparticles were prepared via spray drying from double emulsion (w1/o/w2) utilizing chloroform (CHF) as the organic solvent, l-leucine as a dispersibility enhancer and an internal aqueous phase (w1) containing PEG4500 or Pluronic® F-68 (PLF68). α-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 1H NMR and FT-IR with both analyses confirming PEG incorporated into the polymer backbone, and any unreacted units removed. Optimum formulation α-CH-CHF/PLF68, 1% produced the highest bioactivity, enzyme encapsulation (20.08 ± 3.91%), loading (22.31 ± 4.34 μg/mg), FPF (fine particle fraction) (37.63 ± 0.97%); FPD (fine particle dose) (179.88 ± 9.43 μg), MMAD (mass median aerodynamic diameter) (2.95 ± 1.61 μm), 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 μg/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.