Dry powder inhalation of macromolecules using novel PEG-co-polyester microparticle carriers
Tawfeek, HM; Evans, AR; Iftikhar, A; Mohammed, AR; Shabir, A; Somavarapu, S; Hutcheon, GA; Saleem, IY
| HERO ID | 1940126 |
|---|---|
| In Press | No |
| Year | 2013 |
| Title | Dry powder inhalation of macromolecules using novel PEG-co-polyester microparticle carriers |
| Authors | Tawfeek, HM; Evans, AR; Iftikhar, A; Mohammed, AR; Shabir, A; Somavarapu, S; Hutcheon, GA; Saleem, IY |
| Journal | International Journal of Pharmaceutics |
| Volume | 441 |
| Issue | 1-2 |
| Page Numbers | 611-619 |
| Abstract | 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 (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(®) 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 (1)H 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 5h. 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. |
| Doi | 10.1016/j.ijpharm.2012.10.036 |
| Pmid | 23124106 |
| Wosid | WOS:000314054200073 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Keyword | Microparticles; Pulmonary drug delivery; Macromolecules; Polyester polymer; Dry powder inhalation |