Pathogenesis-Guided Engineering: pH-Responsive Imprinted Polymer Co-Delivering Folate for Inflammation-Resolving as Immunotherapy in Implant-Related Infections

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Costa, Raphael C. ; Nagay, Bruna E. ; Villa, Javier E. L. ; Sotomayor, Maria D. P. T. ; Neres, Lariel Chagas da Silva ; Benso, Bruna ; Aguayo, Sebastian ; Sacramento, Catarina M. ; Ruiz, Karina G. S. ; Spada, Fernanda P. ; de Avila, Erica Dorigatti ; da Costa, Monique G. ; Faverani, Leonardo P. ; Cintra, Luciano T. A. ; Souza, Joao Gabriel S. ; Barao, Valentim A. R.

• Document type: Journal article
• Source: ADVANCED FUNCTIONAL MATERIALS; v. 34, n. 42, p. 16-pg., 2024-07-23.

Abstract

Folate (FT) is a suitable targeting ligand for folate receptors (FOLR) overexpressed on inflamed cells. Thus, FT-loaded polymers can be used as FOLRs-targeted immunotherapy to positively modulate the inflammatory process. A novel biodegradable imprinted polymer with a FT delivery mechanism driven by pH changes [PCL-MIP@FT] is designed with molecularly imprinted technology. The pH mechanism is validated in vitro, demonstrating that an acidic environment accelerated and increased the release of FT for a period of 7 days (similar to 100 mu g mL-1). For the first time, FT receptors (FOLR-1 and FOLR-3) are discovered and also overexpressed on activated human gingival fibroblasts, representing a favorable target in the oral environment. Although FT itself does not have antimicrobial effects, the nanomechanical properties of biofilm are changed after topical FT administration. In vivo systemic toxicity of PCL-MIP@FT has been demonstrated to be a safe biomaterial (up to 1.3 mg kg-1). When the PCL-MIP@FT is assessed in the subcutaneous tissue, it promoted an alleviating inflammation and may be able to stimulate tissue repair. The present findings have demonstrated the reliable in vitro and in vivo anti-inflammatory actions of FT-loaded polymer and support its use as a novel drug-free therapeutic platform for modulating and mitigating inflammatory responses in dental implant-related infections. The biodegradable PCL-based polymers are synthesized and functionalized with folate in a facile manner to achieve suitable release by pH for active participation in inflammatory events involved in dental implant-related infections. This biomaterial has an innovative concept of pathogenesis-guided rational engineering, essentially providing an "on-demand" treatment approach for inflammation bringing together expertise from various fields. image (AU)

• FAPESP's process: 20/05231-4 - Development of a new thermosensitive hydrogel for controlled release of drugs to prevent and treat peri-implant inflammations
• Grantee: Valentim Adelino Ricardo Barão
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/20719-3 - A novel antimicrobial drug-delivery coating for percutaneous implant devices
• Grantee: Érica Dorigatti de Avila
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 20/10436-4 - Synthesis, characterization and biological performance of pH-sensitive nanopolymers produced by molecular printing for the treatment of peri-implant infections
• Grantee: Raphael Cavalcante Costa
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 22/16267-5 - Antimicrobial and osteogenic surface development by electrodeposition of polypyrrole film on titanium surfaces treated by plasma electrolytic oxidation: a multifunctional coating for dental implants
• Grantee: Valentim Adelino Ricardo Barão
• Support Opportunities: Regular Research Grants
• FAPESP's process: 21/09434-0 - A novel antimicrobial drug-delivery coating for percutaneous implant devices
• Grantee: Érica Dorigatti de Avila
• Support Opportunities: Scholarships in Brazil - Young Researchers