Targeted Drug Delivery and Treatment of Endoparasites with Biocompatible Particles of pH-Responsive Structure

Author(s)

Mathews, Patrick D. ^[1] ; Patta, Ana C. M. Fernandes ^[1] ; Goncalves, Joao V. ^[1] ; Gama, Gabriella dos Santos ^[1] ; Garcia, Irene Teresinha Santos ^[2] ; Mertins, Omar ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Paulista Sch Med, Dept Biophys, BR-04023062 Sao Paulo - Brazil

^[2] Univ Fed Rio Grande do Sul, Inst Chem, Dept Phys Chem, BR-91501970 Porto Alegre, RS - Brazil

• Document type: Journal article
• Source: Biomacromolecules; v. 19, n. 2, p. 499-510, FEB 2018.
• Web of Science Citations: 7

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 a drug delivery system via oral administration. The composite particle preparation was in situ monitored by means of isothermal titration calorimetry. The strong interaction established between the macromolecules during particle assembly led to 0.60 alginate/chitosan effective binding sites with an intense exothermic effect and negative enthalpy variation on the order of a thousand kcal/mol. In the presence of model drugs mebendazole and ivermectin, with relatively small and large structures, respectively, mebendazole reduced the amount of chitosan monomers available to interact with alginate by 27%, which was not observed for ivermectin. Nevertheless, a state of intense negative Gibbs energy and, large entropic decrease was achieved, providing evidence that formation of particles is thermodynamically driven and favored. Small-angle X-ray scattering provided further evidence of similar surface aspects independent of the presence of drug. The physical responses of the particles to pH variation comprise partial hydration, swelling, and the predominance of positive surface charge in strong acid medium, whereas ionization followed by deprotonation leads to compaction and charge reversal rather than new swelling in mild and slightly acidic mediums, respectively. In vivo performance was evaluated in the treatment of endoparasites in Colydoras fish. Systematically with a daily base oral administration, particles significantly reduced the infections over 15 days of treatment. The experiments provide evidence that utilizing particles granted and boosted the action of the antiparasitic drugs, leading to substantial reduction or elimination of infection. Hence, the pH-responsive particles represent a biomaterial with prominent characteristics that is promising for the development of targeted oral drug delivery. (AU)

• FAPESP's process: 15/23948-5 - Improvement of the polysaccharide chitosan properties for its application in liposomes and giant vesicles
• Grantee: Omar Mertins
• Support type: Regular Research Grants
• FAPESP's process: 16/13368-4 - Nanostructured systems: from membrane biomimetic models to carriers of bioactives
• Grantee: Karin Do Amaral Riske
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 17/16722-6 - pH responsive nanoparticles for optimization of oral delivery of antiparasite drugs in the treatment of ornamental fish
• Grantee: Ana Carolina Monge Fernandes Patta
• Support type: Scholarships in Brazil - Master