Inhalable dry powder containing lipid polymer hybrid nanoparticles of Nintedanib esylate: In vitro and in vivo evaluations

The key objective of this research work was to develop and evaluate dry powder for inhalation containing lipid polymer hybrid nanoparticles (LPHNPs) loaded with Nintedanib esylate (NE) to target deep lung for the treatment of idiopathic pulmonary fibrosis (IPF). NE loaded LPHNPs (NE-LPHNPs) were prepared by nanoprecipitation method and optimized via Box Behnken Design (BBD). The desirability was found to be 0.905. The optimized NE-LPHNPs exhibited particle size of 99.72 ± 2.60 nm, zeta potential of −26.8 ± 3.2 mV and entrapment efficiency of 88.43 ± 3.90%. Differential scanning calorimetry and X-ray diffraction results showed conversion of NE into an amorphous form. Transmission electron microscopic image depicted discrete, polymeric core and lipid shell structure and spherical shaped LPHNPs. In vitro drug release displayed 96.7 ± 1.9% of release at 28 h and fitted to higuchi model. The dry powder containing lyophilized NE-LPHNPs with inhalac 500 (1:1.5) showed good flow property with mass median aerodynamic diameter of 4 ± 0.2 μm. High deposition into alveolar region was observed by tissue uptake study of fluorescein isothiocyanate loaded LPHNPs. In vivo pulmonary pharmacokinetic study displayed improved area under curve (35.71 fold) than NE suspension. Hence, developed inhalable LPNHPs offers a promising approach for the local delivery of NE.

Materials

NE, N-(carbonyl-methoxypolyethyleneglycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine, sodium salt (DSPE-PEG 2000) and Inhalac 500 were a generous gift from Sun Pharmaceutical Industries Limited (Baroda, India), Lipoid GmbH (Germany) and Signet Excipients Pvt. Ltd. (Bandra, India), respectively. Poly (DL-lactic-co-glycolic acid) (PLGA, 50:50), soy-lecithin and trehalose were purchased from Nomisma healthcare (Baroda, India) and Yarrow Chem Products (Mumbai, India).

Mitali Patel, Sneha Karampuri, Vrushti Kansara, Bhavin Vyas, Inhalable dry powder containing lipid polymer hybrid nanoparticles of Nintedanib esylate: In vitro and in vivo evaluations, Journal of Drug Delivery Science and Technology, 2023, 104716, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2023.104716.

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