Exploiting supramolecular interactions to produce bevacizumab-loaded nanoparticles for potential mucosal delivery

Author(s):Show less -

Ferreira, Leonardo M. B. ^[1] ; Alonso, Jovan D. ^[2] ; Kiill, Charlene P. ^[1] ; Ferreira, Natalia N. ^[1] ; Buzza, Hilde H. ^[3] ; Martins de Godoi, Denis R. ^[2] ; de Britto, Douglas ^[4] ; Assis, Odilio Benedito G. ^[5] ; Seraphim, Thiago V. ^[6] ; Borges, Julio Cesar ^[6] ; Gremiao, Maria Palmira D. ^[1]

Affiliation

^[1] Sao Paulo State Univ, UNESP, Sch Pharmaceut Sci, Rodovia Araraquara Jau Km 1, BR-14801902 Araraquara, SP - Brazil

^[2] Sao Paulo State Univ, UNESP, Inst Chem Araraquara, Araraquara, SP - Brazil

^[3] Univ Sao Paulo, Sao Carlos Inst Phys, Biophoton Lab, Sao Carlos, SP - Brazil

^[4] EMBRAPA, Semiarid, Rodovia BE-428, Km 152, POB 23, Petrolina, PE - Brazil

^[5] EMBRAPA Instrumentat, Rua 15 Novembro, 1-452, POB 741, BR-13560970 Sao Carlos, SP - Brazil

^[6] Univ Sao Paulo, Inst Chem Sao Carlos, Sao Carlos, SP - Brazil

• Document type: Journal article
• Source: EUROPEAN POLYMER JOURNAL; v. 103, p. 238-250, JUN 2018.
• Web of Science Citations: 3

Abstract

Monoclonal antibody (mAb) delivery is gaining importance for local, systemic, and route-specific targeting. The mucus constitutes the main barrier for this type of delivery. In the present study, we aimed to develop a drug delivery platform by integrating mucus penetrating and mucoadhesive agents into a single system. Our hypothesis is that by combining these opposing functions, this system could have its properties modulated according to specific purposes. Self-assembly studies were conducted using three classes of building blocks: the protein drug bevacizumab (BVZ), mucus-penetrating polyanion dextran sulfate (DS), mucoadhesive polycations trimethylchitosan (TMC) and chitosan oligosaccharides (COS). We obtained two types of nanoparticles by manipulating supramolecular interactions between the components. Binary protein-polyanion (BVZ/DS) nano particles showed size of approximately 150 nm and a negative zeta potential. Ternary protein-polyanion-polycation (BVZ/DS/COS) nanoparticles were obtained using COS and exhibited 350 nm and a positive zeta potential. Assisted by calorimetric information, we demonstrated that building stable ternary nanoparticles carrying positive charges were not possible using the polycation TMC due to its thermodynamic constraints. Furthermore, spectroscopy analysis and CAM assay indicated that BVZ continued structurally and functionally stable after its incorporation into the nanoparticles. These two types of nanoparticles exhibited different behaviors when interacting with mucin, as shown by DLS and AFM studies. While the negatively charged particles promoted dispersion of the mucin network, suggesting a mucus penetrating effect of DS, the positively charged particles formed aggregates, probably caused by the mucoadhesive effect of COS. These results highlight the importance of understanding the role of supramolecular interactions, responsible for forming drug delivery systems containing complex molecules, such as proteins and polymers. (AU)

• FAPESP's process: 12/13446-4 - Chitosan-based nanoparticles for intranasal administration of bevacizumab
• Grantee: Leonardo Miziara Barboza Ferreira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/09671-3 - Nanostructured multifunctional systems for drug controlled release through nasal route on glioblastomas treatment
• Grantee: Natália Noronha Ferreira Naddeo
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/16324-0 - Mucoadhesive delivery systems for the release of drugs on intestinal mucosa
• Grantee: Maria Palmira Daflon Gremião
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/10174-3 - EVALUATION OF CHITOSAN NANOPARTICLES FOR DELIVERY OF POTENTIALLY ACTIVE INTEGRINS INHIBITORS IN GLIOBLASTOMAS
• Grantee: Charlene Priscila Kiill
• Support Opportunities: Scholarships in Brazil - Doctorate