The present invention provides, among other things, compositions and methods of formulating nucleic acid-containing nanoparticles comprising no more than three distinct lipids components, one distinct lipid component being a sterol-based cationic lipid. In some embodiments, the present invention provides compositions and methods in which the lipid nanoparticles further comprise helper lipids and PEG-modified lipids. The resulting formulation comprises a high encapsulation percentage for nucleic acids.

The present invention provides for compounds of formula (I) ##STR00001##
wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions mediated and modulated by CFTR, including cystic fibrosis, Sjgren's syndrome, pancreatic insufficiency, chronic obstructive lung disease, and chronic obstructive airway disease. Also provided are pharmaceutical compositions comprised of one or more compounds of formula (I).

This disclosure relates to methods of treating or preventing cystic fibrosis transmembrane conductance regulator (CFTR) mediated diseases such as cystic fibrosis, chronic obstructive pulmonary disease, chronic pancreatitis, chronic bronchitis, asthma, mucus formation, comprising administering an effective amount of a 2-amino-N-benzylidene-acetohydrazide compound or derivative thereof to a subject in need thereof. In certain embodiments, the 2-amino-N-benzylidene-acetohydrazide compound is ((E)-N-(3,5-dibromo-2,4-dihydroxybenzylidene)-2-(m-tolylamino)acetohydrazide; or (E)-N-(3,5-dibromo-2,4-dihydroxybenzylidene)-2-(p-tolylamino)acetohydrazide.

The present invention is directed to methods of inhibiting LTA.sub.4-h in a human patient and method of treating a condition ameliorated by the inhibition of leukotriene A.sub.4 hydrolase activity in a human patient comprising administering to said human patient the compound, 4-{5-[4-(4-Oxazol-2-yl-phenoxy)-benzyl]-2,5-diaza-bicyclo[2.2.1]hept-2-ylmethyl}-benzoic acid.

The invention discloses compounds of Formula (I)

##STR00001##

wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15, R.sup.16, A, R.sup.19, R.sup.20, and R.sup.21 are as defined herein. The present invention relates to deuterated compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treating cystic fibrosis by administering a compound of the invention.

The invention discloses compounds of Formula (I)

##STR00001##

wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15, R.sup.16, A, R.sup.19, R.sup.20, and R.sup.21 are as defined herein. The present invention relates to deuterated compounds and their use in the treatment of cystic fibrosis, methods for their production, pharmaceutical compositions comprising the same, and methods of treating cystic fibrosis by administering a compound of the invention.

Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (ABC) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.

There are provided, inter alia, methods for decreasing mucus elasticity or decreasing mucus viscosity in a subject in need thereof, the methods including administering to the subject an effective amount of a thiosaccharide mucolytic agent, and compounds and pharmaceutical compositions useful for the methods.

Compounds of Formula I: ##STR00001##
pharmaceutically acceptable salts thereof, deuterated derivatives of any of the foregoing, and metabolites of any of the foregoing are disclosed. Pharmaceutical compositions comprising the same, methods of treating cystic fibrosis using the same, and methods for making the same are also disclosed.

This disclosure relates to methods of treating or preventing cystic fibrosis transmembrane conductance regulator (CFTR) mediated diseases such as cystic fibrosis, chronic obstructive pulmonary disease, chronic pancreatitis, chronic bronchitis, asthma, mucus formation, comprising administering an effective amount of a 2-amino-N-benzylidene-acetohydrazide compound or derivative thereof to a subject in need thereof. In certain embodiments, the 2-amino-N-benzylidene-acetohydrazide compound is ((E)-N-(3,5-dibromo-2,4-dihydroxybenzylidene)-2-(m-tolylamino)acetohydrazide; or (E)-N-(3,5-dibromo-2,4-dihydroxybenzylidene)-2-(p-tolylamino)acetohydrazide.