Combined Inhaled Salbutamol and Mannitol Therapy for Mucus Hyper-secretion in Pulmonary Diseases

Abstract

Abstract. This study focuses on the co-engineering of salbutamol sulphate (SS), a common bronchodilator, and mannitol (MA), a mucolytic, as a potential combination therapy for mucus hypersecretion. This combination was chosen to have a synergic effect on the airways: the SS will act on the β 2 -receptor for relaxation of smooth muscle and enhancement of ciliary beat frequency, whilst mannitol will improve the fluidity of mucus, consequently enhancing its clearance from the lung. A series of co-spray-dried samples, containing therapeutically relevant doses of SS and MA, were prepared. The physico-chemical characteristics of the formulations were evaluated in terms of size distribution, morphology, thermal and moisture response and aerosol performance. Additionally, the formulations were evaluated for their effects on cell viability and transport across air interface Calu-3 bronchial epithelial cells, contractibility effects on bronchial smooth muscle cells and cilia beat activity using ciliated nasal epithelial cells in vitro. The formulations demonstrated size distributions and aerosol performance suitable for inhalation therapy. Transport studies revealed that the MA component of the formulation enhanced penetration of SS across the complex mucus layer and the lung epithelia cells. Furthermore, the formulation in the ratios of SS 10 −6 and MA 10 −3 M gave a significant increase in cilia beat frequency whilst simultaneously preventing smooth muscle contraction associated with mannitol administration. These studies have established that co-spray dried combination formulations of MA and SS can be successfully prepared with limited toxicity, good aerosol performance and the ability to increase ciliary beat frequency for improving the mucociliary clearance in patients suffering from hyper-secretory diseases, whilst simultaneously acting on the underlying smooth muscle.

Nanocomposite microparticles (nCmP) for the delivery of tacrolimus in the treatment of pulmonary arterial hypertension

“…First, mannitol is highly water-soluble, which ensures rapid decomposition of nCmP in the aqueous environment of mucus and pulmonary surfactant in the lungs, leading to quick release of NP from the nCmP system. Furthermore, mannitol is able to enhance mucus penetration of nanoparticles by increasing fluidity of mucus in the lung (27). Finally, mannitol has been extensively studied as a carrier in spray-dried powder aerosols for pulmonary drug administration and the resulting particles have been shown to exhibit desirable water content, size, and surface morphology for successful aerosol delivery (28–33).…”

Synthesis and Characterization of Nanocomposite Microparticles (nCmP) for the Treatment of Cystic Fibrosis-Related Infections

“…(23) First, mannitol can be rapidly dissolved into an aqueous environment, leading to a burst release of encapsulated nanoparticles. In addition, mannitol can improve the fluidity of mucus, thus enhancing the mucus penetration rate of nanoparticles (24). Mannitol has been extensively studied as a carrier in spray-dried powder aerosols for pulmonary drug administration and the resulting particles have been shown to exhibit desirable water content, size, and surface morphology for successful aerosol delivery (25, 26).…”

Chelating Behaviour of Dihydrothieno[3,4, d] Pyridazine Derivatives with Some Lanthanide and Actinide Metals

“…The ionic nature of the complexes under investigation can be further confirmed by measurement of the molar conductance values of 110 -3 mol dm - 57 . This reveals a non-electrolytic nature of the synthesized complexes.…”