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 fromTEMPO oxidized cellulose nanofibers (TOCNF). Different formulations were prepared by varyingboth the nanofibers oxidation degree and the relative ratios of branched polyethyleneimine and citricacid, introduced as crosslinkers. The best reaction conditions were achieved using TOCNFcontaining the highest content of carboxylic groups (1.5 mmolCOOH/gTOCNF), which producedmicroparticles with an average diameter below 5 ?m, and a good colloidal stability in aqueousdispersion. Physical-chemical characterization was carried out to study the chemical bonds in themicrosponges matrix, the swelling degree and drug loading and release. Tetracycline, a broad-spectrum drug with pH-dependent amphoteric feature, was chosen as model molecule. Chemicalcrosslinking was verified by spectroscopic characterisation, which revealed the formation of amidebonds. 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 demonstratedby direct and indirect in vitro tests on gastric cancer cells.