Alginate-amphothericin B Nanocomplexes Covered by Nanocrystals From Bacterial Cellulose: Physico-chemical Characterization and in Vitro Toxicity

Abstract

Background: Nanostructured systems free of surfactants have pharmacotechnical and biopharmaceutical advantages, in addition to being a green process. Amphotericin B (AmB) is a drug with anti-leishmanial and anti-fungal potential, but its low water solubility and permeability limit its therapeutic use. Therefore, it could profit from being incorporated into nanostructured systems. In the present study, a self-assembled nanocomplex of alginate (Alg), a polysaccharide extracted from natural sources that can be used in the pharmaceutical area, with AmB was produced in order to improve the limited therapeutic use of this drug (Alg-AmB). Further, as a reinforcing component, cellulose nanocrystals (NCC) were ionically adsorbed into the surface of the nanocomplex systems (Alg-AmB + NCC). Results: Despite some polydispersity (0.523 ± 0.073), this straightforward process allowed to obtain water soluble particles with a hydrodynamic size of 258.87 ± 10.41 nm and charge of -62.93 ± 2.02 mV. Furthermore, the ionic adsorption of the NCC into the Alg-AmB nanocomplex surface was confirmed by an increase in the particle size (466.3 ± 17.57 nm) and a small surface charge decrease (-55.75 ± 1.23 mV). The amorphous inclusion complex of AmB into the polysaccharide chain network in both formulations was confirmed by DSC and FTIR. AmB in the nanocomplexes was in supper-aggregated form and showed good biocompatibility, being significantly less cytotoxic in vitro against kidney cells and significantly less hemolytic comparatively to the free-drug. Conclusions: The results were indicated the Alg-AmB nanocomplex can be considered an economical, non-toxic alternative to improve the AmB therapeutic effect. Furthermore, NCC coating of the nanocomplexes brought additional protection to the system without compromised the advantages attributed to the developed formulation.