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CaAl-layered double hydroxide as a drug delivery system: effects on solubility and toxicity of the antiretroviral efavirenz

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Abstract

The use of layered double hydroxides associated with biologically active molecules is becoming a promising alternative in the development of drug delivery systems that may be applied to drug therapies for different diseases. Efavirenz is an antiretroviral belonging to class II of the biopharmaceutical classification system (low solubility, high permeability). Due to its low aqueous solubility, absorption problems occur in the gastrointestinal tract and, consequently, inadequate oral bioavailability. In this paper, the association between efavirenz and CaAl-layered double hydroxide was obtained by stirring in an acetonic solution until complete evaporation of the solvent. The hybrid material obtained was characterized by X-ray diffraction, differential scanning calorimetry and fourier transform infrared spectroscopy. It was observed that in systems containing up to 30 % of efavirenz, the drug became a molecule with amorphous characteristics and lost its crystalline character. This phenomenon can be demonstrateby the absence of the drug in crystalline plane diffractograms, as well as the absence of its melting point in thermal analysis. In the release test, these systems have been successful in increasing solubility. The system carrier-drug with 30 % of efavirenz was more promising with an increase of 558 % of soluble drug, compared to the drug alone. In antiproliferative activity on human macrophage cell lines, it was observed that the isolate efavirenz presented an IC50 value of 15.71 mg ml−1, while the system carrierdrug with 30 % of efavirenz showed an IC50 value of 20.83 mg ml−1, demonstrating that efavirenz in association with a CaAl-layered double hydroxide provided a reduction in drug toxicity.

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References

  1. Ciobanu, A., Ruellan, S., Mallard, I., landy, D., Gennequin, C., Siffert, S., Siffert, S., Fourmentin, S.: Cyclodextrin-intercalated layered double hydroxides for fragrance release. J. Incl. Phenom. Macrocycl. (2013). doi:10.1007/s10847-012-0227-4

    Google Scholar 

  2. Saber, O., Hatano, B., Tagaya, H.: Preparation of new layered double hydroxide, Co-Ti LDH. J. Incl. Phenom. Macrocycl. 51, 17–25 (2005)

    Article  CAS  Google Scholar 

  3. Takahashi, T., Yamaguchi, M.: Host-guest Interaction swelling clay minerals and poorly water-soluble drugs. 1: Complex formation between a swelling clay mineral and griseofulvin. J. Incl. Phenom. Mol. 10, 283–297 (1991)

    Article  CAS  Google Scholar 

  4. Benes, L., Zima, V.Z., Svoboda, J., Melanova, K.: Intercalation of 2-naphthol-3,6-disulfonate, 9,10-anthraquinone-2,6-disulfonate, and 9,10-anthraquinone-2-sulfonate anions into Zn–Al layered double hydroxide. J. Incl. Phenom. Macrocycl. (2005). doi:10.1007/s10847-005-0663-5

    Google Scholar 

  5. Rives, R., Del Arco, M., Martín, C.: Intercalation of drugs in layered double hydroxides and their controlled release: a review. Appl. Clay Sci. (2014). doi:10.1016/j.clay.2013.12.002

    Google Scholar 

  6. Kanezaki, E.: Unexchangeable interlayer anions; synthesis and characterization of Zn/Aland Mg/Al-layered double hydroxides with interlayer Alizarin red S. J. Incl. Phenom. Macrocycl. 46, 89–95 (2003)

    Article  CAS  Google Scholar 

  7. Feng, J., He, Y., Liu, Y., Du, Y., Li, D.: Supported catalysts based on layered double hydroxides for catalytic oxidation and hydrogenation: general functionality and promising application prospects. Chem. Soc. Rev. (2015). doi:10.1039/C5CS00268K

    Google Scholar 

  8. Sahbaz, Y., Williams, H.D., Nguyen, T., Saunders, T., Ford, L., Charman, S.A., Scammells, P.J., Porter, C.J.H.: Transformation of poorly water-soluble drugs into lipophilic ionic liquids enhances oral drug exposure from lipid based formulations. Mol. Pharm. (2015). doi:10.1021/mp500790t

    Google Scholar 

  9. Vieira, A.C.C., Fontes, D.A.F., Chaves, L.L., Alves, L.D.S., Freitas-neto, J.L., Soares, M.F.R., Soares-sobrinho, J.L., Rolim, L.A., Rolim-neto, P.J.: Multicomponent systems with cyclodextrins and hydrophilic polymers for the delivery of Efavirenz. Carbohyd. Polym. (2015). doi:10.1016/j.carbpol.2015.04.050

    Google Scholar 

  10. Shafiei, S.S., Solati-hashjin, M., Rahim-zadeh, H., Samadikuchaksaraei, A.: Synthesis and characterisation of nanocrystalline Ca–Al layered double hydroxide {[Ca2Al(OH)6]NO3·nH2O}: in vitro study. Adv. Appl. Ceram. (2013). doi:10.1179/1743676112Y.0000000045

    Google Scholar 

  11. Schönherr, D., Wollatz, U., Haznar-Garbacz, D., Hanke, U., Box, K.J., Taylor, R., Ruiz, R., Beato, S., Becker, D., Weitschies, W.: Characterisation of selected active agents regarding pKavalues, solubility concentrations and pH profiles by SiriusT3. Eur. J. Pharm. Biopharm. (2015). doi:10.1016/j.ejpb.2015.02.028

    Google Scholar 

  12. Mosman, T.: Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. lmmunol. Methods 65, 55–63 (1983)

    Article  Google Scholar 

  13. Alves, L.D.S., Soares, M.F.L.R., Albuquerque, C.T., Silva, E.R., Vieira, A.C.C., Fontes, D.A.F., Figueirêdo, C.B.M., Soares-Sobrinho, J.L., Rolim-Neto, P.J.: Solid dispersion of efavirenz in PVP K-30 by conventional solvent and kneading methods. Carbohyd. Polym. (2014). doi:10.1016/j.carbpol.2014.01.027

    Google Scholar 

  14. Wlodarski, K., Sawicki, W., Kozyra, A., Tajber, L.: Physical stability of solid dispersions with respect to thermodynamic solubility of tadalafil in PVP-VA. Eur. J. Pharm. Biopharm. (2015). doi:10.1016/j.ejpb.2015.07.026

    Google Scholar 

  15. Goldenberg, L.M., Wagner, J., Stumpe, J., Paulke, B., Gornitz, E.: Ordered arrays of large latex particles organized by vertical deposition. Langmuir (2002). doi:10.1021/la015659c

    Google Scholar 

  16. Gordijo, C.R., Barbosa, C.A.S., Ferreira, A.M.C., Constantino, V.R.L., Silva, D.O.: Immobilization of ibuprofen and copper-ibuprofen drugs on layered double hydroxides. J. Pharm. Sci. 94(5), 1135–1148 (2005)

    Article  CAS  Google Scholar 

  17. Zhang, P., Qian, G., Xu, Z.P., Shi, H., Ruan, X., Yang, J., Frost, R.L.: Effective adsorption of sodium dodecylsulfate (SDS) by hydrocalumite (CaAl-LDH-Cl) induced by self-dissolution and re-precipitation mechanism. J. Colloid Interface Sci. (2012). doi:10.1016/j.jcis.2011.10.036

    Google Scholar 

  18. Ganesan, P., Soundararajan, R., Shanmugam, U., Ramu, V.: Development, characterization and solubility enhancement of comparative dissolution study of second generation of solid dispersions and microspheres for poorly water soluble drug. Asian J. Pharm. Sci. (2015). doi:10.1016/j.ajps.2015.05.001

    Google Scholar 

  19. Sun, D.D., Lee, P.I.: Evolution of supersaturation of amorphous pharmaceuticals: nonlinear rate of supersaturation generation regulated by matrix diffusion. Mol. Pharm. (2015). doi:10.1021/mp500711c

    Google Scholar 

  20. Sun, D.D., Lee, P.I.: Probing the mechanisms of drug release from amorphous solid dispersions in medium-soluble and medium-insoluble carriers. J. Control. Release (2015). doi:10.1016/j.jconrel.2015.06.004

    Google Scholar 

  21. Vieira, A.C.C., Fontes, D.A.F., Chaves, L.L., Freitas-Neto, J.L., Soares, M.F.L.R., Soares-Sobrinho, J.L., Rolim, L.A., Rolim-Neto, P.J.: Multicomponent systems with cyclodextrins and hydrophilic polymers for the delivery of Efavirenz. Carbohydr. Polym. (2015). doi:10.1016/j.carbpol.2015.04.050

    Google Scholar 

  22. Kim, T., Lee, J., Choi, S., Oh, J.: Polymer coated CaAl-layered double hydroxide nanomaterials for potential calcium supplement. Int. J. Mol. Sci. (2014). doi:10.3390/ijms151222563

    Google Scholar 

  23. Kura, A.U., Hussein-al-ali, S.H., Hussein, M.Z., Fakurazi, S.: Preparation of Tween 80-Zn/Al-levodopa-layered double hydroxides nanocomposite for drug delivery system. Sci. World J. (2014). doi:10.1155/2014/104246

    Google Scholar 

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Acknowledgments

The authors wish to express their gratitude to Laboratory for Pharmaceutical Technology, Federal University of Pernambuco—UFPE/Brazil; Laboratory Biofarmatox, UFPE/Brazil; Laboratory Rare Earths BSTR, UFPE/Brazil; Ping I. Lee Research Group, University of Toronto, Canada, for providing the necessary facilities to develop the present research. This research was supported by Technology Support Foundation of Pernambuco—FACEPE.

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Authors and Affiliations

  1. Technology Laboratory of Medicine, Federal University of Pernambuco, UFPE, Recife, PE, Brazil

    Danilo Augusto Ferreira Fontes, Magaly Andreza Marques de Lyra, Giovanna Christinne Rocha de Medeiros Schver, Larissa Araújo Rolim & Pedro José Rolim-Neto

  2. Core of Medicines and Corelated Quality Control, Federal University of Pernambuco, UFPE, Recife, PE, Brazil

    José Lamartine Soares-Sobrinho

  3. Biofarmatox, Federal University of Pernambuco, UFPE, Recife, PE, Brazil

    Jeyce Kelle Ferreira de Andrade & Teresinha Gonçalves da Silva

  4. Analytical Center of Drugs, Medicines and Food, Federal University of Vale do São Francisco, UNIVASF, Petrolina, PE, Brazil

    Larissa Araújo Rolim

  5. Laboratory Rare Earths BSTR, Federal University of Pernambuco, UFPE, Recife, PE, Brazil

    Severino Alves-Júnior

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  1. Danilo Augusto Ferreira Fontes
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  2. Magaly Andreza Marques de Lyra
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  3. Jeyce Kelle Ferreira de Andrade
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  6. Teresinha Gonçalves da Silva
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  8. Severino Alves-Júnior
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  9. Pedro José Rolim-Neto
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Correspondence to Pedro José Rolim-Neto.

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Fontes, D.A.F., de Lyra, M.A.M., de Andrade, J.K.F. et al. CaAl-layered double hydroxide as a drug delivery system: effects on solubility and toxicity of the antiretroviral efavirenz. J Incl Phenom Macrocycl Chem 85, 281–288 (2016). https://doi.org/10.1007/s10847-016-0627-y

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