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Cyclodextrin inclusion complex of a multi-component natural product by hot-melt extrusion

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Abstract

This study aimed to investigate whether hot-melt extrusion (HME) processing can promote molecular encapsulation of a multi-component natural product composed of volatile and pungent hydrophobic substances (ginger oleoresin (OR)) with cyclodextrins. 6-Gingerol and 6-shogaol, the biomarkers of ginger OR, were quantified by HPLC. Phase-solubility studies were performed using β-cyclodextrin (βCD) and hydroxypropyl-β-cyclodextrin (HPβCD) for ginger OR complexation. Solid complexes were then prepared by thermal (HME)– and solvent (slurry (SL))–based methods. Morphology, thermal behavior, solubility, in vitro dissolution, and in vivo anti-inflammatory activity were evaluated. HPβCD gave rise to AL-type complexes with ginger OR, whereas βCD led to materials with limited solubility. Ginger OR was complexed with HPβCD by HME without significant change in gingerol and shogaol content. Additionally, thermogravimetric analysis (TGA) suggested higher volatile retention in HME complexes than in SL ones. Shogaol and gingerol solubility and dissolution significantly increased from SL and HME complexes compared with ginger OR. In turn, 1:2 OR/HPβCD HME complex showed higher 6-shogaol solubility than SL, associated with a gradual release. The carrageenan-induced pleurisy test showed that the anti-inflammatory activity of ginger OR was maintained after complexation with HPβCD. The complexes significantly decrease the levels of IL-1β and inhibit cell migration. HME complex showed performance equivalent to the positive control and superior to the SL material. Taken together, these results indicate that HME can be useful for promoting the molecular encapsulation of complex natural products that contain volatile and thermolabile substances. HME complexes showed better in vivo and in vitro performance than complexes prepared using the solvent-based method.

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The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank Ashland for kindly supplying the cyclodextrins. We also thank the LABMIC-UFG for the SEM analysis.

Funding

This research was partially supported by the Brazilian agency Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

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Authors and Affiliations

  1. Laboratory of Nanosystems and Drug Delivery Devices (NanoSYS), School of Pharmacy, Universidade Federal de Goiás (UFG), Setor Leste Universitário, Rua 240, Goiânia, GO, 74605-170, Brazil

    Rhayssa de Oliveira Nonato, Anna Paula Krawczyk-Santos, Gleidson Cardoso, Stephania Fleury Taveira & Ricardo Neves Marreto

  2. School of Pharmacy, Universidade Federal de Goiás (UFG), Goiânia, GO, Brazil

    Ana Carolina Kogawa

  3. Pharmaceutical Application Laboratory, Ashland Specialty Ingredients, São Paulo, SP, Brazil

    Karina Ricommini

  4. Pharmacy Department, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil

    Ádley Antonini Neves de Lima

  5. Department of Physiology (DFS), Laboratory of Neuroscience and Pharmacological Assays (LANEF), Universidade Federal de Sergipe, São Cristóvão, SE, Brazil

    Luana Heimfarth & Lucindo José Quintans-Júnior

  6. Laboratory of Food, Drug, and Cosmetics (LTMAC), School of Health Sciences, Universidade de Brasilia, Brasília, DF, Brazil

    Marcílio Cunha-Filho

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Contributions

RNM, KR, SFT, and MC-F conceived the research. RON, RNM, SFT, ACK, LH, LJQ-J, MC-F, and APK-S designed the experiments. RON, GC, and APK-S performed the experiments. RON, RNM, AANL, MC-F, LH, and LJQ-J wrote the paper. All authors read and approved the manuscript.

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Correspondence to Ricardo Neves Marreto.

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Experimental protocols were approved by the Animal Care and Use Committee at the Federal University of Sergipe (Brazil) (CEPA/UFS 8461091121). In addition, the ethical principles established by the Brazilian Society for Laboratory Animal Science and the National Institutes of Health (USA) were respected.

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de Oliveira Nonato, R., Krawczyk-Santos, A.P., Cardoso, G. et al. Cyclodextrin inclusion complex of a multi-component natural product by hot-melt extrusion. Drug Deliv. and Transl. Res. 13, 1140–1152 (2023). https://doi.org/10.1007/s13346-022-01280-w

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