Stable microsponges by spray drying of TEMPO-oxidized cellulose nanofibers: Synthesis and characterization for controlled drug release

A Spray Drying process is presented for one-step production of nanostructured microsponges from TEMPO oxidized cellulose nanofibers (TOCNF). Different formulations were prepared by varying both the nanofibers oxidation degree and the relative ratios of branched polyethyleneimine and citric acid, introduced as crosslinkers. The best reaction conditions were achieved using TOCNF containing the highest content of carboxylic groups (1.5 mmolCOOH/gTOCNF), which produced microparticles with an average diameter below 5 ?m, and a good colloidal stability in aqueous dispersion. Physical-chemical characterization was carried out to study the chemical bonds in the microsponges matrix, the swelling degree and drug loading and release. Tetracycline, a broad- spectrum drug with pH-dependent amphoteric feature, was chosen as model molecule. Chemical crosslinking was verified by spectroscopic characterisation, which revealed the formation of amide bonds. The crosslinked microsponges showed a high drug loading efficiency, as opposed to non- cross-linked ones, and a pH-responsivity in terms of swelling and drug release behaviour. Finally, microsponges derived from formulations without citric acid resulted biocompatible, as demonstrated by direct and indirect in vitro tests on gastric cancer cells.