Antimicrobial and wound healing potential of naphthoquinones encapsulated in nanochitosan

Cyntia Silva Freitas; Patricia Ribeiro Pereira; Raiane Vieira Cardoso; Fernanda Petzold Pauli; Ruan Carlos Busquet Ribeiro; Fernando De Carvalho Da Silva; Vitor Francisco Ferreira; Vania Margaret Flosi Paschoalin

doi:10.3389/fbioe.2023.1284630

Antimicrobial and wound healing potential of naphthoquinones encapsulated in nanochitosan

Front Bioeng Biotechnol. 2024 Jan 4:11:1284630. doi: 10.3389/fbioe.2023.1284630. eCollection 2023.

Authors

Cyntia Silva Freitas¹, Patricia Ribeiro Pereira^{1

2}, Raiane Vieira Cardoso¹, Fernanda Petzold Pauli³, Ruan Carlos Busquet Ribeiro³, Fernando De Carvalho Da Silva³, Vitor Francisco Ferreira⁴, Vania Margaret Flosi Paschoalin^{1

2}

Affiliations

¹ Advanced Analysis Laboratory in Biochemistry and Molecular Biology, Department of Biochemistry, Chemistry Institute, Federal University of Rio De Janeiro, Programa de Pós-Graduação em Ciência de Alimentos, Rio de Janeiro, Brazil.
² Department of Biochemistry, Chemistry Institute, Federal University of Rio De Janeiro, Programa de Pós-Graduação em Química, Rio de Janeiro, Brazil.
³ Applied Organic Synthesis Laboratory, Department of Organic Chemistry, Chemistry Institute, Federal Fluminense University, Niterói, Brazil.
⁴ Department of Pharmaceutical Technology, Faculty of Pharmacy, Federal Fluminense University, Niterói, Brazil.

Abstract

Introduction: The use of chitosan in pharmaceutical formulations is an advantageous approach due to this compound intrinsic biodegradability and biocompatibility, as well as ready availability and low polymer cost. Methods: Herein, the naphthoquinones 3- chloromethylene-menadione (NQ1) and 2,3-dichloro-1,4-naphthoquinone (NQ2) were nanoencapsulated into chitosan (CNP) by the ionotropic gelatinization technique and characterized by DLS, FTIR, SEM, TGA and DSC, and their release profiles evaluated. The antimicrobial and wound healing activities were investigated. Results and Discussion: Homogeneous chitosan nanocapsulses of about 193 nm and Z potential ranging from +30.6 to +33.1 mV loaded with NQ1 (CNP-NQ1) or NQ2 (CNPQNQ2). With nanoencapsulation efficiencies of ≥ 96%, the solubility of naphthoquinones in aqueous environments was improved, making them suitable for biological system applications. The encapsulated naphthoquinones displayed a controlled release of approximately 80% for CNP-NQ1 and 90% for CNP-NQ2 over an 8 h period at 36°C. Both CNP-NQ1 and CNP-NQ2 retained the already established free naphthoquinone antimicrobial activity against two Staphylococcus aureus strains, Staphylococcus epidermidis, Streptococcus pyogenes and Pseudomonas aeruginosa. Although presenting low toxicity to healthy human cells, only CNP-NQ1 displayed therapeutic indices above 100 for S. aureus and S. epidermidis and above 27 for S. pyogenes and P. aeruginosa, allowing for safe use in human tissues. Furthermore, CNP-NQ1 did not impair the migration of human fibroblast cells in scratch assays, adding promising wound healing properties to this formulation. These findings emphasize that CNP-NQ1 may be useful in protecting injured skin tissue from bacterial contamination, avoiding skin infections not only by reducing bacterial loads but also by accelerating the healing process until complete dermal tissue recovery.

Keywords: 2,3-dichloro-1,4-naphthoquinone; 3-chloromethylene-menadione; Pseudomonas aeruginosa; Staphylococcus spp; Streptococcus pyogenes; human fibroblast cells susceptibility; nanocapsules; therapeutic index.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), grant numbers E-26/202.254/2018, E-26/010.101106/2018, E-26/210.865/2019, E-26/201.016/2021, E-26/210.093/2023, E‐26/010.000.984/2019; E-26/204.372/2021, E-26/204.373/2021; E-26/200.756/2023, E-26/200.237/2022, E-26/010/00168/2015, E-26/202.800/2017, E-26/200.911/2021, and SEI-260003/001178/2020. Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), grant numbers 140020/2021-7 and 301873/2019-4.