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

Hesham M. Tawfeek, Andrew R. Evans, Abid Iftikhar, Afzal R. Mohammed, Anjumn Shabir, Satyanarayana Somavarapu, Gillian A. Hutcheon, Imran Y. Saleem

Research output: Contribution to journalArticle

Abstract

This study investigated optimizing the formulation parameters for encapsulation of a model mucinolytic enzyme, a-chymotrypsin (a-CH), within a novel polymer; poly(ethylene glycol)-co-poly(glycerol adipate-co-?-pentadecalactone), PEG-co-(PGA-co-PDL) which were then applied to the formulation of DNase I. a-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). a-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 a-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.
Original languageEnglish
Pages (from-to)611-619
Number of pages9
JournalInternational Journal of Pharmaceutics
Volume441
Issue number1-2
DOIs
Publication statusPublished - 30 Jan 2013

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Polyesters
Chymotrypsin
Poloxamer
Powders
Inhalation
Deoxyribonuclease I
Chloroform
Polymers
Enzymes
Ethylene Glycol
Mucins
Emulsions
Leucine
Lung Diseases
Suspensions
poly(glycerol adipate-co-omega-pentadecalactone)

Cite this

Tawfeek, Hesham M. ; Evans, Andrew R. ; Iftikhar, Abid ; Mohammed, Afzal R. ; Shabir, Anjumn ; Somavarapu, Satyanarayana ; Hutcheon, Gillian A. ; Saleem, Imran Y. / Dry powder inhalation of macromolecules using novel PEG-co-polyester microparticle carriers. In: International Journal of Pharmaceutics. 2013 ; Vol. 441, No. 1-2. pp. 611-619.
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Tawfeek, HM, Evans, AR, Iftikhar, A, Mohammed, AR, Shabir, A, Somavarapu, S, Hutcheon, GA & Saleem, IY 2013, 'Dry powder inhalation of macromolecules using novel PEG-co-polyester microparticle carriers', International Journal of Pharmaceutics, vol. 441, no. 1-2, pp. 611-619. https://doi.org/10.1016/j.ijpharm.2012.10.036

Dry powder inhalation of macromolecules using novel PEG-co-polyester microparticle carriers. / Tawfeek, Hesham M.; Evans, Andrew R.; Iftikhar, Abid; Mohammed, Afzal R.; Shabir, Anjumn; Somavarapu, Satyanarayana; Hutcheon, Gillian A.; Saleem, Imran Y.

In: International Journal of Pharmaceutics, Vol. 441, No. 1-2, 30.01.2013, p. 611-619.

Research output: Contribution to journalArticle

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T1 - Dry powder inhalation of macromolecules using novel PEG-co-polyester microparticle carriers

AU - Tawfeek, Hesham M.

AU - Evans, Andrew R.

AU - Iftikhar, Abid

AU - Mohammed, Afzal R.

AU - Shabir, Anjumn

AU - Somavarapu, Satyanarayana

AU - Hutcheon, Gillian A.

AU - Saleem, Imran Y.

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AB - This study investigated optimizing the formulation parameters for encapsulation of a model mucinolytic enzyme, a-chymotrypsin (a-CH), within a novel polymer; poly(ethylene glycol)-co-poly(glycerol adipate-co-?-pentadecalactone), PEG-co-(PGA-co-PDL) which were then applied to the formulation of DNase I. a-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). a-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 a-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.

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