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.

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In this paper, a series of cellulose-based hydrophobic associating polymers were prepared by homogeneous acylation of microcrystalline cellulose with long-chain acyl chlorides including octanoyl, lauroyl, and palmitoly chlorides in the solvent of N,N-dimethylacetamide/lithium chloride (DMAc/LiCl) using pyridine as acid scavenger. Through controlling the chain length of fatty acyl chlorides and the molar ratio of acyl chlorides vs anhydroglucose unit, the hydrophobic cellulose derivatives with degrees of substitution in the range of 0.02-1.75 were successfully obtained. The chemical structures and properties of these hydrophobic derivatives were characterized by elemental analysis, FT-IR, CP/MAS 13 C NMR, X-ray diffraction, and the thermogravimetry analysis. It was also found that, the cellulose-based polymers achieved an excellent solubility in organic solvents, such as benzene, methylbenzene, and pyridine, with the introduction of hydrophobic side chain into the cellulose backbone. Furthermore, it was found that these hydrophobic cellulose derivatives could self-assemble into spherical nanoparticles in aqueous solution, which indicates a tremendous potential of applications in pharmaceutical and medical fields.