Fucoidan-based bosutinib nanocrystals for pulmonary drug delivery: Solid state characterization and in-vitro assessment

Abstract

Biopolymer based nanomedicine for pulmonary delivery is safe and effective in lung cancer therapy. Current work addressed marine polysaccharide fucoidan fabricated bosutinib nanocrystals (FBNC) as dry powder for inhalation (DPI). Microscopic characterization uncovered the cubic-shaped amorphous nanocrystals of about 150 nm with high homogeneity (polydispersity index < 0.3). The lyophilized nanocrystals were stable for 6 months at 4 ℃ and contained approximately 50 % drug. The solid-state characterization of FBNC including FTIR, XRD, DSC, XPS, solid-state NMR and BET revealed the conversion of crystalline bosutinib to amorphous nanocrystals with about 10-fold increase in surface area and saturation solubility. An in-vitro drug release study in simulated lung fluid showed over five-fold improvement in drug dissolution by nanocrystals than coarse drugs. The mucus permeation efficiency of nanocrystal also increased over five-times than coarse drug. The flow property analysis and aerosolization investigation revealed excellent flowability and good aerosolization performance (ED: 70–80 % and FPD: 40–60 %) indicating the nanocrystals capability in drug delivery to deep lungs. In conclusion, polysaccharide fucoidan stabilized bosutinib nanocrystals can be a novel drug delivery system for pulmonary administration as dry powder for inhalation.

Keywords

• Nanocrystals
• Solubility
• Pulmonary drug delivery
• Nanomedicine
• Solid state characterization