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

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 cells in vitro were further determined. In vitro and in vivo studies showed almost complete drug release and drug absorption from the lungs in the initial 2 h for pure BUD, which were sustained up to 12 h from BUD loaded into nanosponges (BUD-βCD-NS). Acute toxicity studies and in vitro cytotoxicity studies on alveolar cells proved the safety of BUD-βCD-NS. Several parameters, including particle size, median mass aerodynamic diameter, % fine particle fraction, and % emitted dose, were evaluated for aerosol performance, suggesting the capability of BUD-βCD-NS to formulate as a dry powder inhaler (DPI) with a suitable diluent. To sum up, this research will offer new insights into the future advancement of βCD-NS as drug delivery systems for providing controlled release of therapeutic agents against pulmonary disease. [ABSTRACT FROM AUTHOR]