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Year 2020, Volume: 50 Issue: 3, 251 - 255, 30.12.2020

Abstract

References

  • • Alsenz, J., Steffen, H., & Alex, R. (1998). Active apical secretory efflux of the HIV protease inhibitors saquinavir and ritonavir in Caco-2 cell monolayers. Pharmaceutical Research, 15(3), 423–428. https://doi.org/10.1023/A:1011924314899
  • • Chowdary, K. P. R., Annamma Devi, D. G., & Dhanalakshmi, K. (2012). A factorial study on enhancement of solubility and dissolution rate of ibuprofen by hydroxy propyl β cyclodextrin and solutol hs15. International Journal of Pharmaceutical Sciences Review and Research, 2(4), 1–7.
  • • Holmstock, N., Annaert, P., & Augustijns, P. (2012). Boosting of HIV protease inhibitors by ritonavir in the intestine: The relative role of cytochrome P450 and P-glycoprotein inhibition based on Caco-2 monolayers versus in situ intestinal perfusion in mice. Drug Metabolism and Disposition, 40(8), 1473–1477. https://doi. org/10.1124/dmd.112.044677
  • • Janneh, O., Jones, E., Chandler, B., Owen, A., & Khoo, S. H. (2007). Inhibition of P-glycoprotein and multidrug resistance-associated proteins modulates the intracellular concentration of lopinavir in cultured CD4 T cells and primary human lymphocytes. Journal of Antimicrobial Chemotherapy, 60(5), 987–993. https://doi. org/10.1093/jac/dkm353
  • • Karakucuk, A., Celebi, N., & Teksin, Z. S. (2016). Preparation of ritonavir nanosuspensions by microfluidization using polymeric stabilizers: I. A Design of Experiment approach. European Journal of Pharmaceutical Sciences, 95, 111–121. https://doi.org/10.1016/j. ejps.2016.05.010
  • • Karakucuk, Alptug, Teksin, Z. S., Eroglu, H., & Celebi, N. (2019). Evaluation of improved oral bioavailability of ritonavir nanosuspension. European Journal of Pharmaceutical Sciences, 131(February), 153–158. https://doi.org/10.1016/j.ejps.2019.02.028
  • • Koga, K., Ohyashiki, T., Murakami, M., & Kawashima, S. (2000). Modification of ceftibuten transport by the addition of non-ionic surfactants. European Journal of Pharmaceutics and Biopharmaceutics, 49(1), 17–25. https://doi.org/10.1016/S0939-6411(99)00059-4
  • • Lenhardt, T., Vergnault, G., Grenier, P., Scherer, D., & Langguth, P. (2008). Evaluation of nanosuspensions for absorption enhancement of poorly soluble drugs: In vitro transport studies across intestinal epithelial monolayers. AAPS Journal, 10(3), 435–438. https://doi.org/10.1208/s12248-008-9050-7
  • • Matsumoto, T., Kaifuchi, N., Mizuhara, Y., Warabi, E., & Watanabe, J. (2018). Use of a Caco-2 permeability assay to evaluate the effects of several Kampo medicines on the drug transporter P-glycoprotein. Journal of Natural Medicines, 72(4), 897–904. https://doi. org/10.1007/s11418-018-1222-x
  • • Miller, D. W., Batrakova, E. V, & Kabanov, A. V. (1999). Inhibition of multidrug resistance-associated protein (MRP) functional activity with pluronic block copolymers. Pharmaceutical Research, 16(3), 396–401. https://doi.org/10.1023/A:1018873702411
  • • Perloff, M. D., Von Moltke, L. L., Marchand, J. E., & Greenblatt, D. J. (2001). Ritonavir induces P-glycoprotein expression, multidrug resistance-associated protein (MRP1) expression, and drug transporter-mediated activity in a human intestinal cell line. Journal of Pharmaceutical Sciences, 90(11), 1829–1837. https://doi. org/10.1002/jps.1133
  • • Rege, B. D., Yu Lawrence, X., Hussain, A. S., & Polli, J. E. (2001). Effect of common excipients on Caco-2 transport of low-permeability drugs. Journal of Pharmaceutical Sciences, 90(11), 1776–1786. https://doi.org/10.1002/jps.1127
  • • Rehman, S., Nabi, B., Fazil, M., Khan, S., Bari, N. K., Singh, R., Ahmad, S., Kumar, V., Baboota, S., & Ali, J. (2017). Role of P-Glycoprotein Inhibitors in the Bioavailability Enhancement of Solid Dispersion of Darunavir. BioMed Research International, 2017, 1–17. https://doi. org/10.1155/2017/8274927
  • • Riss, T. L., Moravec, R. A., Niles, A. L., Duellman, S., Benink, H. A., Worzella, T. J., & Minor, L. (2016). Cell viability assays. In Assay Guidance Manual [Internet]. Eli Lilly & Company and the National Center for Advancing Translational Sciences.
  • • Salazar, J., Heinzerling, O., Müller, R. H., & Möschwitzer, J. P. (2011). Process optimization of a novel production method for nanosuspensions using design of experiments (DoE). International Journal of Pharmaceutics, 420(2), 395–403. https://doi.org/10.1016/j. ijpharm.2011.09.003
  • • Schmitt, C., Kaeser, B., Riek, M., Bech, N., & Kreuzer, C. (2010). Effect of saquinavir/ritonavir on P-glycoprotein activity in healthy volunteers using digoxin as a probe. International Journal of Clinical Pharmacology and Therapeutics, 48(3), 192–199. https://doi. org/10.5414/CPP48192
  • • Sinha, S., Ali, M., Baboota, S., Ahuja, A., Kumar, A., & Ali, J. (2010). Solid dispersion as an approach for bioavailability enhancement of poorly water-soluble drug ritonavir. AAPS PharmSciTech, 11(2), 518–527. https://doi.org/10.1208/s12249-010-9404-1
  • • Tashan, E., Karakucuk, A., & Celebi, N. (2019). Optimization and in vitro evaluation of ziprasidone nanosuspensions produced by a top-down approach. Journal of Drug Delivery Science and Technology, 52(March), 37–45. https://doi.org/10.1016/j.jddst.2019.04.024

Evaluation of Caco-2 cell permeability of ritonavir nanosuspensions

Year 2020, Volume: 50 Issue: 3, 251 - 255, 30.12.2020

Abstract

Background and Aims: Poor aqueous solubility limits drug absorption through intestinal mucosa. Nanosuspensions with nanometer range particle size provides enhanced aqueous solubility and hence permeability. The objective of this study was to investigate the cytotoxicity and in vitro cell permeability through human adenocarcinoma (Caco-2) cells of ritonavir (RTV) nanosuspensions. Methods: The Microfluidization method was used to prepare nanosuspensions. Particle size (PS), polydispersity index (PI) and zeta potential (ZP) values were measured as characterization. MTT test was applied to evaluate the cytotoxic effect. Caco-2 cell lines were used for transport studies with RTV coarse powder, physical mixtures and nanosuspension. Results: Approximately 600 nm PS, 0.4 PDI and 22 mV ZP values were observed for nanosuspensions. The sample groups showed no cytotoxicity on the cell lines in any RTV concentration. However, significant cytotoxic effect was determined in groups with high amounts of sodium dodecyl sulfate. The transported RTV in nanosuspension formulation enhanced by 5.3- fold and 1.5-fold in comparison with RTV coarse powder and physical mixture, respectively. Rate of the transportation and also the amount of the transported RTV were improved with nanosuspension formulation. Conclusion: Particle size reduction of RTV into nanometer size and preparing nanosuspension system was found effective to obtain enhanced cell permeability.

References

  • • Alsenz, J., Steffen, H., & Alex, R. (1998). Active apical secretory efflux of the HIV protease inhibitors saquinavir and ritonavir in Caco-2 cell monolayers. Pharmaceutical Research, 15(3), 423–428. https://doi.org/10.1023/A:1011924314899
  • • Chowdary, K. P. R., Annamma Devi, D. G., & Dhanalakshmi, K. (2012). A factorial study on enhancement of solubility and dissolution rate of ibuprofen by hydroxy propyl β cyclodextrin and solutol hs15. International Journal of Pharmaceutical Sciences Review and Research, 2(4), 1–7.
  • • Holmstock, N., Annaert, P., & Augustijns, P. (2012). Boosting of HIV protease inhibitors by ritonavir in the intestine: The relative role of cytochrome P450 and P-glycoprotein inhibition based on Caco-2 monolayers versus in situ intestinal perfusion in mice. Drug Metabolism and Disposition, 40(8), 1473–1477. https://doi. org/10.1124/dmd.112.044677
  • • Janneh, O., Jones, E., Chandler, B., Owen, A., & Khoo, S. H. (2007). Inhibition of P-glycoprotein and multidrug resistance-associated proteins modulates the intracellular concentration of lopinavir in cultured CD4 T cells and primary human lymphocytes. Journal of Antimicrobial Chemotherapy, 60(5), 987–993. https://doi. org/10.1093/jac/dkm353
  • • Karakucuk, A., Celebi, N., & Teksin, Z. S. (2016). Preparation of ritonavir nanosuspensions by microfluidization using polymeric stabilizers: I. A Design of Experiment approach. European Journal of Pharmaceutical Sciences, 95, 111–121. https://doi.org/10.1016/j. ejps.2016.05.010
  • • Karakucuk, Alptug, Teksin, Z. S., Eroglu, H., & Celebi, N. (2019). Evaluation of improved oral bioavailability of ritonavir nanosuspension. European Journal of Pharmaceutical Sciences, 131(February), 153–158. https://doi.org/10.1016/j.ejps.2019.02.028
  • • Koga, K., Ohyashiki, T., Murakami, M., & Kawashima, S. (2000). Modification of ceftibuten transport by the addition of non-ionic surfactants. European Journal of Pharmaceutics and Biopharmaceutics, 49(1), 17–25. https://doi.org/10.1016/S0939-6411(99)00059-4
  • • Lenhardt, T., Vergnault, G., Grenier, P., Scherer, D., & Langguth, P. (2008). Evaluation of nanosuspensions for absorption enhancement of poorly soluble drugs: In vitro transport studies across intestinal epithelial monolayers. AAPS Journal, 10(3), 435–438. https://doi.org/10.1208/s12248-008-9050-7
  • • Matsumoto, T., Kaifuchi, N., Mizuhara, Y., Warabi, E., & Watanabe, J. (2018). Use of a Caco-2 permeability assay to evaluate the effects of several Kampo medicines on the drug transporter P-glycoprotein. Journal of Natural Medicines, 72(4), 897–904. https://doi. org/10.1007/s11418-018-1222-x
  • • Miller, D. W., Batrakova, E. V, & Kabanov, A. V. (1999). Inhibition of multidrug resistance-associated protein (MRP) functional activity with pluronic block copolymers. Pharmaceutical Research, 16(3), 396–401. https://doi.org/10.1023/A:1018873702411
  • • Perloff, M. D., Von Moltke, L. L., Marchand, J. E., & Greenblatt, D. J. (2001). Ritonavir induces P-glycoprotein expression, multidrug resistance-associated protein (MRP1) expression, and drug transporter-mediated activity in a human intestinal cell line. Journal of Pharmaceutical Sciences, 90(11), 1829–1837. https://doi. org/10.1002/jps.1133
  • • Rege, B. D., Yu Lawrence, X., Hussain, A. S., & Polli, J. E. (2001). Effect of common excipients on Caco-2 transport of low-permeability drugs. Journal of Pharmaceutical Sciences, 90(11), 1776–1786. https://doi.org/10.1002/jps.1127
  • • Rehman, S., Nabi, B., Fazil, M., Khan, S., Bari, N. K., Singh, R., Ahmad, S., Kumar, V., Baboota, S., & Ali, J. (2017). Role of P-Glycoprotein Inhibitors in the Bioavailability Enhancement of Solid Dispersion of Darunavir. BioMed Research International, 2017, 1–17. https://doi. org/10.1155/2017/8274927
  • • Riss, T. L., Moravec, R. A., Niles, A. L., Duellman, S., Benink, H. A., Worzella, T. J., & Minor, L. (2016). Cell viability assays. In Assay Guidance Manual [Internet]. Eli Lilly & Company and the National Center for Advancing Translational Sciences.
  • • Salazar, J., Heinzerling, O., Müller, R. H., & Möschwitzer, J. P. (2011). Process optimization of a novel production method for nanosuspensions using design of experiments (DoE). International Journal of Pharmaceutics, 420(2), 395–403. https://doi.org/10.1016/j. ijpharm.2011.09.003
  • • Schmitt, C., Kaeser, B., Riek, M., Bech, N., & Kreuzer, C. (2010). Effect of saquinavir/ritonavir on P-glycoprotein activity in healthy volunteers using digoxin as a probe. International Journal of Clinical Pharmacology and Therapeutics, 48(3), 192–199. https://doi. org/10.5414/CPP48192
  • • Sinha, S., Ali, M., Baboota, S., Ahuja, A., Kumar, A., & Ali, J. (2010). Solid dispersion as an approach for bioavailability enhancement of poorly water-soluble drug ritonavir. AAPS PharmSciTech, 11(2), 518–527. https://doi.org/10.1208/s12249-010-9404-1
  • • Tashan, E., Karakucuk, A., & Celebi, N. (2019). Optimization and in vitro evaluation of ziprasidone nanosuspensions produced by a top-down approach. Journal of Drug Delivery Science and Technology, 52(March), 37–45. https://doi.org/10.1016/j.jddst.2019.04.024
There are 18 citations in total.

Details

Primary Language English
Subjects Pharmacology and Pharmaceutical Sciences, Health Care Administration
Journal Section Original Article
Authors

Alptuğ Karaküçük 0000-0002-9061-2427

Naile Öztürk This is me 0000-0002-7617-8433

Nevin Çelebi This is me 0000-0002-6402-5042

Publication Date December 30, 2020
Submission Date April 13, 2020
Published in Issue Year 2020 Volume: 50 Issue: 3

Cite

APA Karaküçük, A., Öztürk, N., & Çelebi, N. (2020). Evaluation of Caco-2 cell permeability of ritonavir nanosuspensions. İstanbul Journal of Pharmacy, 50(3), 251-255.
AMA Karaküçük A, Öztürk N, Çelebi N. Evaluation of Caco-2 cell permeability of ritonavir nanosuspensions. iujp. December 2020;50(3):251-255.
Chicago Karaküçük, Alptuğ, Naile Öztürk, and Nevin Çelebi. “Evaluation of Caco-2 Cell Permeability of Ritonavir Nanosuspensions”. İstanbul Journal of Pharmacy 50, no. 3 (December 2020): 251-55.
EndNote Karaküçük A, Öztürk N, Çelebi N (December 1, 2020) Evaluation of Caco-2 cell permeability of ritonavir nanosuspensions. İstanbul Journal of Pharmacy 50 3 251–255.
IEEE A. Karaküçük, N. Öztürk, and N. Çelebi, “Evaluation of Caco-2 cell permeability of ritonavir nanosuspensions”, iujp, vol. 50, no. 3, pp. 251–255, 2020.
ISNAD Karaküçük, Alptuğ et al. “Evaluation of Caco-2 Cell Permeability of Ritonavir Nanosuspensions”. İstanbul Journal of Pharmacy 50/3 (December 2020), 251-255.
JAMA Karaküçük A, Öztürk N, Çelebi N. Evaluation of Caco-2 cell permeability of ritonavir nanosuspensions. iujp. 2020;50:251–255.
MLA Karaküçük, Alptuğ et al. “Evaluation of Caco-2 Cell Permeability of Ritonavir Nanosuspensions”. İstanbul Journal of Pharmacy, vol. 50, no. 3, 2020, pp. 251-5.
Vancouver Karaküçük A, Öztürk N, Çelebi N. Evaluation of Caco-2 cell permeability of ritonavir nanosuspensions. iujp. 2020;50(3):251-5.