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

• Published in: International journal of pharmaceutics Vol. 441; no. 1-2; pp. 611 - 619
• Main Authors: Tawfeek, Hesham M., Evans, Andrew R., Iftikhar, Abid, Mohammed, Afzal R., Shabir, Anjum, Somavarapu, Satyanarayana, Hutcheon, Gillian A., Saleem, Imran Y.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.01.2013
• Subjects: Administration, Inhalation; Animals; biodegradability; breathing; Bronchi - cytology; Bronchi - metabolism; chemical structure; chloroform; Chymotrypsin - administration & dosage; Chymotrypsin - pharmacology; deoxyribonuclease I; Deoxyribonuclease I - administration & dosage; Deoxyribonuclease I - pharmacology; dispersibility; Drug Carriers - chemistry; Drug Delivery Systems; Dry powder inhalation; Dry Powder Inhalers; Emulsions; encapsulation; Epithelial Cells - metabolism; ethylene glycol; Fourier transform infrared spectroscopy; glycerol; Humans; Macromolecules; Microparticles; Microspheres; mucins; Mucins - metabolism; nuclear magnetic resonance spectroscopy; Particle Size; Poloxamer - chemistry; Polyester polymer; Polyesters - chemistry; Polyethylene Glycols - chemistry; polymers; Pulmonary drug delivery; respiratory tract diseases; solvents; spray drying; Swine; Time Factors; Pulmonary drug delivery; Dry powder inhalation; Polyester polymer; Macromolecules; Microparticles
• DOI: 10.1016/j.ijpharm.2012.10.036
• ISSN: 0378-5173

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±4.34μg/mg), FPF (fine particle fraction) (37.63±0.97%); FPD (fine particle dose) (179.88±9.43μg), MMAD (mass median aerodynamic diameter) (2.95±1.61μm), 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±3.27μg/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.