Inhaled extended-release microparticles of heparin elicit improved pulmonary pharmacodynamics against antigen-mediated airway hyper-reactivity and inflammation

Advantages and challenges of the spray-drying technology for the production of pure drug particles and drug-loaded polymeric carriers

“…[26, 35,101] and PLGA [44,74,82,98,[102][103][104][105][106], or hydrophilic ones such as chitosan [25,45,56,94,[107][108][109][110][111], alginate [37,112], poly(vinylpyrrolidone) (PVP) [113,114], hydroxypropylmethylcellulose (HPMC) [69] and gelatin [50,115] are initially dissolved in organic or aqueous solvents, respectively, and then spray-dried. In the former, the main advantage is the use of solvents with low boiling point.…”

Low-Molecular-Weight Heparin (LMWH)–Loaded Large Porous PEG-PLGA Particles for the Treatment of Asthma

“…(38) Similarly, in a mouse model, unfractionated heparin-loaded PLGA particles showed significantly heightened pharmacodynamic response against airway hyper-reactivity and inflammation compared with plain heparin. (12) Heparins are reported to significantly reduce bronchial hyper-reactivity in asthmatic patients challenged with external stimuli. (39,40) Owing to shorter duration and mechanisms involved in anti-inflammatory activities of plain heparin, these effects were largely limited to the early-phase response.…”

“…(18,19) The goal of the formulation-based approaches was to produce a continuous release of the drug in the lung and reduce bleeding complications associated with systemic exposure. For example, heparin encapsulated in chitosan nanoparticles (20,21) and inhalable poly(D,L-lactideco-glycolide) (PLGA) microparticles (12) is shown to be efficacious in the treatment of asthma and other inflammatory conditions. However, these studies evaluated only the influence of unfractionated heparin on the release of mediators from mast cells (20,21) or airway hyper-reactivity.…”

“…However, these studies evaluated only the influence of unfractionated heparin on the release of mediators from mast cells (20,21) or airway hyper-reactivity. (12) There are no systematic studies concerning the use of biocompatible and biodegradable particles as carriers for inhalational delivery of LMWH, smaller fragments of unfractionated heparin, for the treatment of asthma.…”