title: Formulation of pH responsive peptides as inhalable dry powders for pulmonary delivery of nucleic acids.
abstract: Nucleic acids have the potential to be used as therapies or vaccines for many different types of disease, but delivery remains the most significant challenge to their clinical adoption. pH responsive peptides containing either histidine or derivatives of 2,3-diaminopropionic acid (Dap) can mediate effective DNA transfection in lung epithelial cells with the latter remaining effective even in the presence of lung surfactant containing bronchoalveolar lavage fluid (BALF), making this class of peptides attractive candidates for delivering nucleic acids to lung tissues. To further assess the suitability of pH responsive peptides for pulmonary delivery by inhalation, dry powder formulations of pH responsive peptides and plasmid DNA, with mannitol as carrier, were produced by either spray drying (SD) or spray freeze drying (SFD). The properties of the two types of powders were characterised and compared using scanning electron microscopy (SEM), next generation impactor (NGI), gel retardation and in vitro transfection via a twin stage impinger (TSI) following aerosolisation by a dry powder inhaler (Osmohaler™). Although the aerodynamic performance and transfection efficacy of both powders were good, the overall performance revealed SD powders to have a number of advantages over SFD powders and are the more effective formulation with potential for efficient nucleic acid delivery through inhalation.
authors.affiliation: Department of Pharmacology & Pharmacy, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region.
authors.forename: Wanling
authors.initials: W
authors.lastname: Liang
authors.affiliation: Department of Pharmacology & Pharmacy, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region; Faculty of Pharmacy, The University of Sydney, Australia.
authors.forename: Philip C L
authors.initials: PC
authors.lastname: Kwok
authors.affiliation: Department of Pharmacology & Pharmacy, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region.
authors.forename: Michael Y T
authors.initials: MY
authors.lastname: Chow
authors.affiliation: Faculty of Pharmacy, The University of Sydney, Australia.
authors.forename: Patricia
authors.initials: P
authors.lastname: Tang
authors.affiliation: Institute of Pharmaceutical Science, King's College London, United Kingdom.
authors.forename: A James
authors.initials: AJ
authors.lastname: Mason
authors.affiliation: Faculty of Pharmacy, The University of Sydney, Australia.
authors.forename: Hak-Kim
authors.initials: HK
authors.lastname: Chan
authors.affiliation: Department of Pharmacology & Pharmacy, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region. Electronic address: jkwlam@hku.hk.
authors.forename: Jenny K W
authors.initials: JK
authors.lastname: Lam
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000295:instrumentation; D058995:Dry Powder Inhalers; D004847:Epithelial Cells / Q000378:metabolism*; D004867:Equipment Design; D005612:Freeze Drying; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008168:Lung / Q000378:metabolism*; D008969:Molecular Sequence Data; D010316:Particle Size; D010455:Peptides / Q000737:chemistry*; D010957:Plasmids; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties; D014162:Transfection
chemical_list: D004337:Drug Carriers; D010455:Peptides; D004247:DNA
keywords: Gene delivery; Non-viral vector; Peptides; Pulmonary delivery; Spray drying; Spray freeze drying; pH responsive