DOI: 10.1021/acs.biomac.7b01630
http://pubs.acs.org/doi/abs/10.1021/acs.biomac.7b01630
ABSTRACT
Biomaterials conceived for vectorization of bioactives are currently considered for biomedical, biological and environmental applications. We have produced a pH sensitive biomaterial composed of natural source alginate and chitosan polysaccharides for application as drug delivery system via oral administration. The composite particles preparation was in situ monitored by means of isothermal titration calorimetry. The strong interaction established between the macromolecules during particles assembling lead to 0.60 alginate/chitosan effective binding sites, with intense exothermic effect and negative enthalpy variation in the order of thousand kcal/mol. In presence of model drugs mebendazole and ivermectin, of relative small and large structure respectively, mebendazole reduced 27% the amount of chitosan monomers available to interact with alginate, which was not observed for ivermectin. Despite, a state of intense negative Gibbs energy and large entropic decrease was achieved evidencing that formation of particles is thermodynamically driven and favored. Small angle Xray scattering further evidenced similar surface aspect independently of drugs absence or presence. The physical responses of the particles to pH variation comprise partial hydration, swelling and predominance of positive surface charge in strong acid medium, while ionization followed by deprotonation leads to compaction and charge reversal than new swelling respectively in mild and slight acid mediums. In vivo performance was evaluated in treatment of endoparasites in Corydoras fish. Systematically in a daily base oral administration, particles reduced significantly the infections in 15 days of treatment. The experiments evidenced that utilization of particles granted and boosted the action of the anti-parasitic drugs, leading to substantial reduction or elimination of infection. Hence, the pH responsive particles represent a biomaterial of prominent characteristics liable to development of target oral drug delivery.
- KEYWORDS: Composite bioparticles; Isothermal titration calorimetry; SAXS; Parasitosis; In vivo application; Prevalence.
