title: Dry powder inhalation of macromolecules using novel PEG-co-polyester microparticle carriers.
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.
authors.affiliation: School of Pharmacy & Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.
authors.forename: Hesham M
authors.initials: HM
authors.lastname: Tawfeek
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Evans
authors.forename: Abid
authors.initials: A
authors.lastname: Iftikhar
authors.forename: Afzal R
authors.initials: AR
authors.lastname: Mohammed
authors.forename: Anjum
authors.initials: A
authors.lastname: Shabir
authors.forename: Satyanarayana
authors.initials: S
authors.lastname: Somavarapu
authors.forename: Gillian A
authors.initials: GA
authors.lastname: Hutcheon
authors.forename: Imran Y
authors.initials: IY
authors.lastname: Saleem
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D002918:Chymotrypsin / Q000008:administration & dosage* / Q000494:pharmacology; D003850:Deoxyribonuclease I / Q000008:administration & dosage* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D058995:Dry Powder Inhalers; D004655:Emulsions; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D008863:Microspheres; D009077:Mucins / Q000378:metabolism; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D013552:Swine; D013997:Time Factors
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D009077:Mucins; D011091:Polyesters; C568823:poly(glycerol adipate-co-omega-pentadecalactone); D020442:Poloxamer; D011092:Polyethylene Glycols; D003850:Deoxyribonuclease I; D002918:Chymotrypsin; C117608:alpha-chymotrypsin