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Synthesis of Submicrometric Chitosan Particles Loaded with Calcium Phosphate for Biomedical Applications

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Abstract

Chitosan particles loaded with dibasic calcium phosphate anhydrous (DCPA) is a promising strategy for combining antimicrobial and osteoconduction properties in regenerative medicine. However, mostly micrometer-sized particles have been reported in the literature, limiting their use and reducing their effect in the biomedical field. We have recently overcome this limitation by developing submicrometer-sized particles with electrospray technique. The objective of this study was to understand how the process parameters control the size and properties of submicrometer chitosan particles loaded with DCPA. Solutions of 10 mg/mL chitosan and 2.5 mg/mL DCPA in a 90% acetic acid were electrosprayed under three distinct flow rate conditions: 0.2, 0.5, and 1.0 mL/h. The particles were crosslinked in a glutaraldehyde atmosphere and characterized in terms of their morphology, inorganic content, zeta potential, and minimum inhibitory concentration (MIC) against S. mutans. All conditions showed particles with two similar morphologies: one small-sized with a spherical shape and another larger-sized with a bi-concave shape. All generated a broad particle size distribution, with a similar mean size of ~ 235 nm. The addition of DCPA decreased the zeta potential for all the samples, but it was above 30 mV, indicating a low aggregation potential. The lower flow rate showed the worst efficacy for DCPA incorporation. Antimicrobial activity was greater in chitosan/DCPA particles with flow rate of 0.5 mL/h. It can be concluded that the flow rate of 0.5 mL/h presents the best compromise solution in terms of morphology, zeta potential, MIC, and inorganic content.

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Acknowledgements

The authors thank the São Paulo Research Foundation, Brazil (FAPESP, 2016/13114-2), along with the FAPESP-UNSW Joint Research Grant Program, Brazil-Australia (FAPESP, 2017/50290-6) for funding this project.

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Authors and Affiliations

  1. Departamento de Odontologia, Universidade Ibirapuera, Av. Interlagos 1329 – 4° andar, São Paulo, SP, 04661-100, Brazil

    Diana Pereira Lopes, Lucia Nobuco Takamori Kikuchi & Maria Stella Moreira

  2. Faculdade de Odontologia, Universidade Santo Amaro, Av. Prof. Eneas de Siqueira Neto, 340, São Paulo, SP, 04829-900, Brazil

    Selma Regina Muniz Freitas, Leticia Cristina Cidreira Boaro & Flávia Gonçalves

  3. Centre for Rural Dentistry & Oral Health, Charles Sturt University, Orange, NSW, 2800, Australia

    Carina Baptiston Tanaka

  4. Departamento de Química Fundamental, Instituto de Química da Universidade de São Paulo, Av. Prof. Lineu Prestes, 748, São Paulo, SP, 05508-000, Brazil

    Giovanne Delechiave & Luiz Henrique Catalani

  5. Faculdade de Odontologia da Universidade de São Paulo, Departamento de Biomateriais e Biologia Oral, Av. Prof. Lineu Prestes, 2222, São Paulo, SP, 05508-000, Brazil

    Roberto R. Braga

  6. School of Mechanical and Manufacturing Engineering, University of New South Wales (UNSW Sydney), Sydney, NSW, 2052, Australia

    Jamie J. Kruzic

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  1. Diana Pereira Lopes
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Contributions

Lopes DP – chitosan purification, particles synthesis, TGA and drafting of the manuscript

Freitas SEM – MIC analysis, and drafting of the manuscript

Tanaka CB - conception, data interpretation and drafting of the manuscript

Delechiave G – zeta potential, DSC, and drafting of the manuscript

Kikuchi LNT – ninhydrin assay, FTIR and drafting of the manuscript

Braga RR - conception, data interpretation and reviewing of the manuscript

Kruzic JJ - conception, data interpretation and reviewing of the manuscript

Boaro LCC – MIC analysis, data interpretation and reviewing of the manuscript

Catalani LH - conception, data interpretation and reviewing of the manuscript

Moreira SM – ICO-OES, data interpretation and reviewing of the manuscript

Gonçalves F – MEV, statistical analysis conception, data interpretation and reviewing of the manuscript

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Correspondence to Leticia Cristina Cidreira Boaro.

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Lopes, D.P., Freitas, S.R.M., Tanaka, C.B. et al. Synthesis of Submicrometric Chitosan Particles Loaded with Calcium Phosphate for Biomedical Applications. AAPS PharmSciTech 24, 56 (2023). https://doi.org/10.1208/s12249-023-02517-8

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