Pharmaceutical strategies to extend pulmonary exposure of inhaled medicines

Abstract

Pulmonary administration route has been extensively exploited for the treatment of local lung diseases such as asthma, chronic obstructive pulmonary diseases and respiratory infections, and systemic diseases such as diabetes. Most inhaled medicines could be cleared rapidly from the lungs and their therapeutic effects are transit. The inhaled medicines with extended pulmonary exposure may not only improve the patient compliance by reducing the frequency of drug administration, but also enhance the clinical benefits to the patients with improved therapeutic outcomes. This article systematically reviews the physical and chemical strategies to extend the pulmonary exposure of the inhaled medicines. It starts with an introduction of various physiological and pathophysiological barriers for designing inhaled medicines with extended lung exposure, which is followed by recent advances in various strategies to overcome these barriers. Finally, the applications of the inhaled medicines with extended lung exposure for the treatment of various diseases and the safety concerns associated to various strategies to extend the pulmonary exposure of the inhaled medicines are summarized.

Keywords: ALIS, amikacin liposomal inhalation suspension; API, active pharmaceutical ingredient; BALF, bronchoalveolar lavage fluid; COPD, chronic obstructive pulmonary diseases; CS, chitosan; DPIs, dry powder inhalers; DPPC, dipalmitoylphosphatidylcholine; DSPC, 1,2-distearoyl-sn-glycero-3-phosphocholine; Da, aerodynamic diameters; ELF, epithelial lining fluid; FDA, US food and drug administration; FDKP, fumaryl diketopiperazine; HA, hyaluronic acid; IL-4, interleukin-4; IL-5, interleukin-5; Inhaled sustained release formulations; LABA, long-acting β2-adrenoceptor agonist; LPPs, large porous particles; Local lung diseases; MCE, mucociliary escalator; MDIs, metered dose inhalers; MP, mucoadhesive particles; MPP, mucus-penetrating particles; MW, molecular weight; Mn, number-average molecular weight; NLCs, nanostructured lipid carriers; PCL, poly-ε-caprolactone; PDD, pulmonary drug delivery; PEG, polyethylene glycol; PK, pharmacokinetics; PLA, polylactic acid; PLGA, poly(lactic-co-glycolic acid); PVA, polyvinyl alcohol; Pharmaceutical strategies; Pulmonary clearance pathways; Pulmonary drug delivery; Pulmonary exposure; Pulmonary safety; SLNs, solid lipid nanoparticles; Systemic diseases; Tmax, time of maximum concentration.