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    Co-spray-dried poly-L-lysine with L-leucine as dry powder inhalations for the treatment of pulmonary infection: Moisture-resistance and desirable aerosolization performance

    Year: 2022

    Journal: Int. J. Pharm., Volume 624, AUG 25

    Authors: Zhang, Xuejuan; Zhou, Yue; Wang, Guanlin; Zhao, Ziyu; Jiang, Zhongxiang; Cui, Yingtong; Yue, Xiao; Huang, Zhengwei; Huang, Ying; Pan, Xin; Wu, Chuanbin

    Organizations: National Natural Science Foundation of China [82104072, 82104070]; Guangzhou Science and Technology Plan Project [202201010424, 202201010589]; Fundamental Research Funds for the Central Uni-versities [21621014]

    Keywords: Dry powder inhalations; Poly-L-lysine; Pulmonary infection; Aerosolization performance; Moisture-resistance

    Poly-L-lysine (PLL) is a promising candidate for the treatment of pulmonary infection with lower occurrence of drug-resistance due to its unique antibacterial mechanisms. Dry powder inhalations (DPIs) are considered as the first choice for formulating PLL to treat pulmonary infection on account of direct delivery and satisfactory stability. However, hygroscopicity of PLL limited its therapeutic effect on pulmonary infection when PLL developed into DPIs. The hygroscopicity caused two obstacles including the low drug deposition in the lower respiratory tract and undesirable aerosolization performance deterioration. In this study, PLL was co-spray-dried with L-leucine (LL) to achieve moisture-resistance and desirable aerosolization performance. The ratio of PLL and LL was optimized to obtain particles with different morphology, hygroscopicity and aerodynamic properties. The obtained PLL DPIs were suitable for inhalation with a corrugated surface formed by hydrophobic LL. The anti -hygroscopicity, aerosolization performance and rheological properties of P2 DPIs were optimal when PLL:LL = 85:15. The DPIs particles were stable after being stored at high relative humidity (60 +/- 5%), and their superi-ority in treating pulmonary infections was also proved by in vitro and in vivo experiments. The established PLL DPIs were proved to be a feasible and desirable approach to treat pulmonary infections.
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