A pharmaceutical formulation comprising polymeric nanoparticles encapsulated within cross-linked polymeric microparticles is provided wherein the polymeric nanoparticles carry a therapeutic agent suitable for the treatment of pulmonary arterial hypertension (PAH) loaded within them, for use in the treatment of PAH. The polymeric nanoparticles may comprise a chitosan a chitosan-derivative polymer selected from chitosan-PEG, N-trimethyl chitosan or a derivative of chitosan comprising a stearic acid, cholanic acid, phthaloyl or butyl acrylate side chain poly(lactic-co-glycolic acid) or a self-assembly amphiphilic chitosan derivative selected from chitosan-PEG-cholanic acid, chitosan-PEG-stearic acid or chitosan-PEG-oleic acid. Preferably the cross-linked polymeric microparticles are cross-linked hydrogel polymeric microparticles that are pH responsive and comprise self-interpenetrating polymeric networks (semi-IPNs) or full-IPNs. Preferably the cross-linked polymeric micrparticles comprise chitosan or a water soluble chitosan derivative, such as carboxymethyl and PEGylated derivatives. Preferably the microparticles further comprise one or more polymers selected from hyaluronate, carrageenan and oligoguluronate. Preferably the therapeutic agent is selected from prostacyclin synthetic analogues, PPAR β agonists and NO donors, in particular the therapeutic agent is a protacyclin synthetic analogue selected from treprostinil or selexipag. Preferred formulations are inhalable, dry powder pharmaceutical formulations, which are able to swell on administration to the lungs of a patient.
