Design of mucoadhesive gellan gum and chitosan nanoparticles intended for colon-specific delivery of peptide drugs

Author(s)

de Oliveira Cardoso, Valeria Maria ^[1] ; Pereira de Brito, Natalia Araujo ^[1] ; Ferreira, Natalia Noronha ^[1] ; Boni, Fernanda Isadora ^[1] ; Barboza Ferreira, Leonardo Miziara ^[1] ; Carvalho, Suzana Goncalves ^[1] ; Daflon Gremiao, Maria Palmira ^[1]

Affiliation

^[1] Sao Paulo State Univ, Sch Pharmaceut Sci, UNESP, Rodovia Araraquara, Jau Km 01, Araraquara, SP - Brazil

• Document type: Journal article
• Source: COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS; v. 628, NOV 5 2021.
• Web of Science Citations: 0

Abstract

Nanotechnology has been widely used in the development of polymer nanocarriers for the oral delivery of biomolecules. The use of nanostructured systems can improve drug delivery and help to overcome the disadvantages of the oral administration of peptides. Nanoparticles (NPs) based on gellan gum (GG) and chitosan (CS) blends were prepared through polyelectrolyte complexation. The influence of pH on the zeta potential (ZP) of polymers allowed the selection of pH 5.0 as the most suitable pH for the complexation of polyelectrolytes. The effects of the polymer mass ratio and addition order on the formation and physicochemical properties of the NPs were evaluated. All NPs showed high positive ZP (> + 30 mV), which ensures electrostatic stability. The order of addition of the polymers influenced the particle size. Nanoscale structures (575.30-974.60 nm) were formed when GG (0.5-3 mg) was dripped into the CS dispersion (0.75-4.5 mg); however, when CS was dripped in the GG dispersion, particle aggregation occurred (sizes >5000 nm). Polymyxin B (PMB) nanoencapsulation reduced the particle size, mainly at low GG mass (1.5 mg). The PMB-polymer interactions were detected by Fourier transform infrared spectroscopy. The X-ray diffraction data indicated the formation of more organized structures with a higher degree of crystallinity. Scanning electron microscopy revealed spherical and uniform NPs. The mucoadhesive capability of the NPs was also demonstrated. The NP2\_1 and NP2\_3 released the lowest amount of drug in HCl 0.1 N (pH 1.2) (<29%), and the drug release rate was controlled in a phosphate buffer 0.1 M (pH 6.8) (<60%). The important findings of this study suggest that nanocarriers with tailored properties may be utilized to overcome the challenges of oral administration of peptides, such as PMB, contributing to the advances in the search for alternatives to the oral administration of PMB. (AU)

• FAPESP's process: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach
• Grantee: Maria Vitória Lopes Badra Bentley
• Support Opportunities: Research Projects - Thematic Grants
• 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: 15/21412-0 - Gellan/retrograded starch mucoadhesives systems intended for the colonic release of bevacizumab to cancer treatment.
• Grantee: Valéria Maria de Oliveira Cardoso
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/04546-1 - Evaluation of synergic effect between CHC and cetuximab against glioblastoma using drug delivery systems
• Grantee: Natália Noronha Ferreira Naddeo
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate