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Design of Magnetic Polymeric Particles as a Stimulus-Responsive System for Gastric Antimicrobial Therapy

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Abstract

The treatment of peptic ulcers induced by H. pylori remains challenging due to the deep mucous layer location of bacteria preventing antimicrobial drug access. The present work aimed to design and evaluate in vitro dual responsive (both pH and magnetic field-sensitive) polymeric magnetic particles loaded with amoxicillin as a smart drug carrier for deep mucous layer penetration and in situ drug release. Magnetite particles were produced by the co-precipitation method and subsequently coated with the Eudragit®S100 and amoxicillin by using the spray-drying technique. The physicochemical characterization of the obtained particles was carried out by optical and scanning electron microscopy, X-ray powder diffraction, Fourier transform infrared spectroscopy, nitrogen adsorption/desorption isotherms, and vibrating sample magnetometry. Additionally, drug release tests and antibacterial activity tests were evaluated in vitro. Microparticles presented 17.2 ± 0.4 μm in size and their final composition was 4.3 ± 1.5% of amoxicillin, 87.0 ± 2.3% of Eudragit, and 9.0 ± 0.3% of magnetite. They were both pH and magnetic field responsive while presenting antimicrobial activity. On one side, magnetic field responsiveness of particles is expected to prompt them to reach bacterium niche in deep mucous layer by means of magnetic forces. On the other side, pH responsiveness is expected to enable drug release in the neutral pH of the deep mucous layer, preventing undesired delivery in the acidic gastric lumen. Smart microparticles were designed presenting both pH and magnetic field responsiveness as well as antimicrobial activity. These may be promising assets for peptic ulcer treatment.

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Acknowledgements

This research was partially supported by the Brazilian research agencies Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). The authors are grateful to the Núcleo de Petróleo de Gás Natural (NEPGN, UFRN) for the SEM images, to the Fundação Oswaldo Cruz (Fiocruz/RJ, Brazil) for the bacterial strain and to the Centro de Tecnologias Estratégicas do Nordeste (CETENE) for the NSD and BET/BJH analysis and to the Laboratório Central Dr. Almino Fernandes (LACEN-RN) for the microbiological analysis.

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Authors and Affiliations

  1. Departamento de Análises de Produtos e Ambiente, Setor de Análise de Medicamentos, Laboratório Central Dr. Almino Fernandes, Natal, RN, Brazil

    Erica L. Silva-Freitas

  2. Departamento de Farmácia, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil

    Erica L. Silva-Freitas, Thales R. F. Pontes, Rafael P. Araújo-Neto, Ítalo H. M. Damasceno, Kátia L. Silva, Juliana F. Carvalho & Eryvaldo S. T. Egito

  3. Departamento de Cirurgia, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil

    Aldo C. Medeiros

  4. Departamento de Física Teórica e Experimental, Universidade Federal do Rio Grande do Norte, UFRN, Avenida Senador Salgado Filho, 3000, 59078-970, Natal, RN, Brazil

    Rodolfo B. Silva, Marco A. Morales & Artur S. Carriço

  5. Laboratoire Matière et Systèmes Complexes, UMR 7057, CNRS, Université Paris Diderot, Paris, France

    Amanda K. A. Silva

  6. Departamento de Física, Universidade do Estado do Rio Grande do Norte, Mossoró, RN, Brazil

    Ana L. Dantas

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  1. Erica L. Silva-Freitas
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Correspondence to Artur S. Carriço.

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Silva-Freitas, E.L., Pontes, T.R.F., Araújo-Neto, R.P. et al. Design of Magnetic Polymeric Particles as a Stimulus-Responsive System for Gastric Antimicrobial Therapy. AAPS PharmSciTech 18, 2026–2036 (2017). https://doi.org/10.1208/s12249-016-0673-1

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