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Compatibilized Biopolymer-based Core–shell Nanoparticles: A New Frontier in Malaria Combo-therapy

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Abstract

Purpose

Nano-sized biopolymer-based strategies such as spatio-temporal co-delivery of bioactives could be employed to overcome low bioavailability of antimalarial drugs delivered by conventional dosage forms in malaria combo-therapy. This work reports on the development of core–shell nanocarrier using a biocomposite containing Prosopis africana gum (PG) and microcrystalline cellulose (MCC) for spatio-temporal delivery of artemether and lumefantrine (AL) to enhance oral malaria treatment.

Methods

The biocomposite was prepared by pH-dependent temperature-controlled coacervation and characterized by differential scanning calorimetry, thermogravimetric measurements, and time-domain nuclear magnetic resonance relaxometry. Nanocarrier containing AL was produced using the combination of high-shear homogenization and nanoprecipitation techniques, characterized regarding physicochemical performance, in-vitro dissolution and stability. In-vivo studies were performed in mice infected with Plasmodium berghei parasite.

Results

Biocomposite containing 1:1 ratio of PG:MCC gave the best physicochemical properties. The nanoparticles were spherical with a smooth surface, gave encapsulation efficiency of 81.23 ± 1.54% and 57.15 ± 0.86% for artemether and lumefantrine, respectively, and exhibited an average size of 208.29 ± 0.94 nm, a low polydispersity index value (0.141 ± 0.02) indicating a narrow size distribution and a positive charge of 34.51 ± 1.05 mV. The nanoparticles provided a quick release for artemether and a slow release for lumefantrine within 8 h, indicating the suitability for spatio-temporal drug delivery in malaria combo-therapy. Optimized AL-loaded nanoformulation was stable, histopathologically safe on major organs implicated in malaria and exhibited greater antimalarial activity than marketed AL.

Conclusion

These results postulate the developed core–shell nanocarrier as versatile drug co-delivery nanoplatform and potential alternative approach to improve the pharmacodynamics of AL combo-therapies in malaria treatment.

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Acknowledgements

Dr. Franklin Chimaobi Kenechukwu greatly appreciates the mentorship of Prof. Dr. Marcos Lopes Dias and his research team for providing a good working condition for this research. The various contributions of the laboratory staff of Instituto de Macromoléculas Professora Eloisa Mano (IMA) and Nanomedicines Unit, Facultade de Pharmacia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro-RJ, Brazil, are highly acknowledged.

Funding

The present work has been done with the financial support from the Brazilian National Council for Scientific and Technological Development (CNPq) — Brazil and The World Academy of Sciences (TWAS) — for the advancement of science in developing countries (Italy) (Grant FR number: 3240299288). This research work received support from the Tertiary Education Trust Fund (TETFund) (Grant No. TETFUND/DR&D/CE/NRF/2019/STI/46/) by Government of Nigeria.

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Authors and Affiliations

  1. Drug Delivery and Nanomedicines Research Group, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria, Enugu State, 410001, Nigeria

    Franklin Chimaobi Kenechukwu

  2. Instituto de Macromoléculas Professora Eloisa Mano (IMA), Universidade Federal Do Rio de Janeiro (UFRJ), Rio de Janeiro-RJ, Brazil

    Franklin Chimaobi Kenechukwu, Marcos Lopes Dias & Roberto Pinto Cucinelli Neto

  3. Facultade de Pharmacia, Nanomedicines Unit, Universidade Federal Do Rio de Janeiro (UFRJ), Rio de Janeiro-RJ, Brazil

    Eduardo Ricci-Júnior

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Franklin Chimaobi Kenechukwu: conceptualization, methodology, validation, resources, formal analysis, investigation, funding acquisition, writing — original and draft as well as revision. Marcos Lopes Dias: conceptualization, methodology, validation, resources, funding acquisition, supervision, project administration, writing — review and editing. Roberto Pinto Cucinelli Neto: conceptualization, methodology, validation, resources, formal analysis, investigation, writing. Eduardo Ricci-Júnior: conceptualization, methodology, validation, resources, supervision, writing – review and editing.

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Kenechukwu, F.C., Dias, M.L., Neto, R.P.C. et al. Compatibilized Biopolymer-based Core–shell Nanoparticles: A New Frontier in Malaria Combo-therapy. J Pharm Innov 18, 594–620 (2023). https://doi.org/10.1007/s12247-022-09664-8

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