Preparation and evaluation of βcyclodextrin-based nanosponges loaded with Budesonide for pulmonary delivery

• Published in: International journal of pharmaceutics 2023-11, Vol.647, p.123529-123529, Article 123529
• Main Authors: Salem, Yasmein Yaser, Hoti, Gjylije, Sammour, Rana M.F., Caldera, Fabrizio, Cecone, Claudio, Matencio, Adrián, Shahiwala, Aliasgar F., Trotta, Francesco
• Format: Article
• Language: English
• Subjects: Budesonide; Cyclodextrin nanosponges; Dry powder inhaler; In vitro and in vivo studies; Pulmonary disease
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2023.123529

This research work was intended to formulate a novel inhaled product (Budesonide βCD-based NS) for providing the controlled release of Budesonide. [Display omitted] •β-cyclodextrin (βCD), a cyclic oligosaccharide consisting of seven glucose units, was chemically crosslinked with various crosslinking agents such as pyromellitic dianhydride (PMDA), 1, 1′-carbonyldiimidazole (CDI), citric acid (CA), and 1,4-butanediol diglycidyl ether (BDE), and thus βCD-based nanosponges (βCD-NS) were prepared.•Budesonide (BUD) was loaded into five different βCD-NS at four ratios (BUD: NS; 1:1; 1:2; 1:3; 1:4 w:w) using three methods (labelled as methods A, B, and C). CDI-based βCD-NS presented a higher encapsulation efficiency (∼80 %) of BUD at the ratio of BUD: NS 1:3 w:w.•The optimized formulations were successfully characterized by FTIR Spectroscopy analysis, TGA analysis, water absorption capacity (WAC), scanning electron microscopy (SEM), X-ray powder diffraction studies (XRD), and by the measurement of the particle size, zeta potential, encapsulation efficiency, in vitro and in vivo release studies, in vitro/ in vivo correlation and in vitro cytotoxicity on alveolar cells, acute toxicity study, solid-state characterization, and aerosol performance suggesting the potential role of βCD-NS as a pulmonary drug delivery carrier.•In vivo animal studies proposed sustained drug release in the lungs for 12 h which may result in reduced dosing frequency and improved patient convenience and compliance. Budesonide (BUD) is a glucocorticosteroid used to treat chronic obstructive pulmonary disease. Despite this, it is a hydrophobic compound with low bioavailability. To address these hurdles, non-toxic and biocompatible βcyclodextrin-based nanosponges (βCD-NS) were attempted. BUD was loaded on five different βCD-NS at four different ratios. NS with 1,1′-carbonyldiimidazole (CDI) as a crosslinking agent, presented a higher encapsulation efficiency ( ̴ 80%) of BUD at 1:3 BUD: βCD-NS ratio (BUD-βCD-NS). The optimized formulations were characterized by Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), water absorption capacity (WAC), scanning electron microscopy (SEM), X-ray powder diffraction studies (XRD), particle size, zeta potential, encapsulation efficiency, in vitro and in vivo release studies, acute toxicity study, solid-state characterization, and aerosol performance. In vitro-in vivo correlation and cytotoxicity of the formulations on alveolar ce