Facile development of nanocomplex-in-nanoparticles for enhanced loading and selective delivery of doxorubicin to brain

Abstract

Aim: Facile development of polysaccharides-based carrier system for efficient delivery of doxorubicin (DOX) to the brain. Methods: DOX was nanocomplexed with alginate (Alg) followed by incorporation into chitosan (Cs) nanomatrices. The resulting carriers were optimized to have a net positive charge improving their delivery across the blood–brain barrier. The optimum DOX-loaded nanosystem was targeted to brain tissue via loading into various nasal dosage forms. Results: The pH-dependent ionization of both DOX and Alg was found to have a significant effect on DOX entrapment efficiency which was improved from 4% at slightly acidic media to 85% using different pHs. The nasal dosage forms, especially the insert, delivered the loaded DOX mostly to the brain tissue with targeting efficiency reaching 480%. Conclusion: New intranasal carrier system was developed with efficient targeting of DOX to the brain. The carrier has potential to be used for delivery of other drugs acting on CNS. Graphical abstract: [Formula: see text]