Development of paclitaxel and flurbiprofen coloaded PLGA nanoparticles: understanding critical formulation and process parameters using Plackett– Burman design

Year 2019, Volume: 49 Issue: 3, 161 - 166, 01.12.2019

Adem SAHİN Secil CABAN-TOKTAS Hayrettin TONBUL Firat YERLİKAYA Yesim AKTAS Yilmaz CAPAN

Abstract

DOI: 10.26650/IstanbulJPharm.2019.19036

Nano drug co-delivery system is a popular strategy for combined application of two or more anticancer and/or synergistic drugs. Synergistic effects of nonsteroidal anti-inflammatory drugs and anti-cancer drugs in cancer treatment are shown in the literature. In this study, it was aimed to screen and understand critical formulation and process parameters inthe preparationflurbiprofen and paclitaxel co-loaded nanoparticles for developing an anti-cancer nano co-delivery system. With this aim, critical parameters were determined using Plackett–Burman experimental design (DoE). Flurbiprofen and paclitaxel drug loading amounts were considered as critical quality attributes to controleffective drug loading ratio. Furthermore, average particle size and zeta potential were also defined as critical quality attributes in order to optimize passive drug targeting and colloidal stability. Surfactant type was determined as the most significant factors for the average particle size and zeta potential. For flurbiprofen and paclitaxel drug loading into the nanoparticles, amounts of both flurbiprofen and paclitaxel were determined as critical factors. Consequently, paclitaxel and flurbiprofen were efficiently loaded into nanoparticles and the impact of the formulation variables were successfully screened by a DoE. By controlling the determined parameters, therapeutic efficacy of co-loaded drug nanoparticles could be maximized in further studies.

You may cite this article as: Şahin A, Çaban-Toktaş S, Tonbul H, Yerlikaya F, Aktaş Y, Çapan Y (2019). Development of Paclitaxel and Flurbiprofen Co-Loaded PLGA Nanoparticles: Understanding Critical Formulation and Process Parameters Using Plackett–Burman Design. Istanbul J Pharm 10.26650/IstanbulJPharm.2019.19036.

Keywords

Nanoparticles, paclitaxel, flurbiprofen, PLGA, design of experiments, Plackett–Burman

References

• Acharya, S., & Sahoo, S. K. (2011). PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect. Advanced Drug Delivery Reviews, 63(3), 170-183. doi:https://doi.org/10.1016/j.addr.2010.10.008 Collnot, E. M., Baldes, C., Schaefer, U. F., Edgar, K. J., Wempe, M. F., & Lehr, C. M. (2010). Vitamin E TPGS P-glycoprotein inhibition mechanism: influence on conformational flexibility, intracellular ATP levels, and role of time and site of access. Mol Pharm, 7(3), 642-651. doi:10.1021/mp900191s Danhier, F., Ansorena, E., Silva, J. M., Coco, R., Le Breton, A., & Preat, V. (2012). PLGA-based nanoparticles: an overview of biomedical applications. J Control Release, 161(2), 505-522. doi:10.1016/j.jconrel.2012.01.043 Dinarvand, R., Sepehri, N., Manoochehri, S., Rouhani, H., & Atyabi, F. (2011). Polylactide-co-glycolide nanoparticles for controlled delivery of anticancer agents. Int J Nanomedicine, 6, 877-895. doi:10.2147/ijn.s18905 Gaonkar, R. H., Ganguly, S., Dewanjee, S., Sinha, S., Gupta, A., Ganguly, S., . . . Chatterjee Debnath, M. (2017). Garcinol loaded vitamin E TPGS emulsified PLGA nanoparticles: preparation, physicochemical characterization, in vitro and in vivo studies. Scientific Reports, 7(1), 530. doi:10.1038/s41598-017-00696-6 Hillaireau, H., & Couvreur, P. (2009). Nanocarriers' entry into the cell: relevance to drug delivery. Cell Mol Life Sci, 66(17), 2873-2896. doi:10.1007/s00018-009-0053-z Jin, H., Wang, Z., Liu, L., Gao, L., Sun, L., Li, X., . . . Fan, D. (2010). R-flurbiprofen reverses multidrug resistance, proliferation and metastasis in gastric cancer cells by p75(NTR) induction. Mol Pharm, 7(1), 156-168. doi:10.1021/mp900189x Jin, H., Wang, Z., Liu, L., Gao, L., Sun, L., Li, X., . . . Fan, D. (2010). R-Flurbiprofen Reverses Multidrug Resistance, Proliferation and Metastasis in Gastric Cancer Cells by p75NTR Induction. Molecular Pharmaceutics, 7(1), 156-168. doi:10.1021/mp900189x Kozlu, S., Sahin, A., Ultav, G., Yerlikaya, F., Calis, S., & Capan, Y. (2018). Development and in vitro evaluation of doxorubicin and celecoxib co-loaded bone targeted nanoparticles. Journal of Drug Delivery Science and Technology, 45, 213-219. doi:https://doi.org/10.1016/j.jddst.2018.02.004 Liu, J. K., Patel, S. K., Gillespie, D. L., Whang, K., & Couldwell, W. T. (2012). R-flurbiprofen, a novel nonsteroidal anti-inflammatory drug, decreases cell proliferation and induces apoptosis in pituitary adenoma cells in vitro. J Neurooncol, 106(3), 561-569. doi:10.1007/s11060-011-0712-4 Ma, P., & Mumper, R. J. (2013). Paclitaxel Nano-Delivery Systems: A Comprehensive Review. J Nanomed Nanotechnol, 4(2), 1000164. doi:10.4172/2157-7439.1000164 Malvern. Zeta Potential An Introduction in 30 Minutes Retrieved from https://www.materials-talks.com/wp-content/uploads/2017/09/mrk654-01_an_introduction_to_zeta_potential_v3.pdf Ostolska, I., & Wiśniewska, M. (2014). Application of the zeta potential measurements to explanation of colloidal Cr(2)O(3) stability mechanism in the presence of the ionic polyamino acids. Colloid and polymer science, 292(10), 2453-2464. doi:10.1007/s00396-014-3276-y Qi, S. S., Sun, J. H., Yu, H. H., & Yu, S. Q. (2017). Co-delivery nanoparticles of anti-cancer drugs for improving chemotherapy efficacy. Drug Deliv, 24(1), 1909-1926. doi:10.1080/10717544.2017.1410256. Rahman, Z., Zidan, A. S., Habib, M. J., & Khan, M. A. (2010a). Understanding the quality of protein loaded PLGA nanoparticles variability by Plackett-Burman design. International Journal of Pharmaceutics, 389(1-2), 186-194. doi:10.1016/j.ijpharm.2009.12.040 Rahman, Z., Zidan, A. S., Habib, M. J., & Khan, M. A. (2010b). Understanding the quality of protein loaded PLGA nanoparticles variability by Plackett–Burman design. International Journal of Pharmaceutics, 389(1–2), 186-194. doi:http://dx.doi.org/10.1016/j.ijpharm.2009.12.040 Saadati, R., & Dadashzadeh, S. (2014). Marked effects of combined TPGS and PVA emulsifiers in the fabrication of etoposide-loaded PLGA-PEG nanoparticles: in vitro and in vivo evaluation. Int J Pharm, 464(1-2), 135-144. doi:10.1016/j.ijpharm.2014.01.014 Sahin, A., Esendagli, G., Yerlikaya, F., Caban-Toktas, S., Yoyen-Ermis, D., Horzum, U., . . . Capan, Y. (2017). A small variation in average particle size of PLGA nanoparticles prepared by nanoprecipitation leads to considerable change in nanoparticles' characteristics and efficacy of intracellular delivery. Artif Cells Nanomed Biotechnol, 45(8), 1657-1664. doi:10.1080/21691401.2016.1276924 Sahin, A., Esendagli, G., Yerlikaya, F., Caban-Toktas, S., Yoyen-Ermis, D., Horzum, U., . . . Capan, Y. (2017). A small variation in average particle size of PLGA nanoparticles prepared by nanoprecipitation leads to considerable change in nanoparticles’ characteristics and efficacy of intracellular delivery. Artificial Cells, Nanomedicine, and Biotechnology, 45(8), 1657-1664. doi:10.1080/21691401.2016.1276924 Sahin, A., Spiroux, F., Guedon, I., Arslan, F. B., Sarcan, E. T., Ozkan, T., . . . Capan, Y. (2017). Using PVA and TPGS as combined emulsifier in nanoprecipitation method improves characteristics and anticancer activity of ibuprofen loaded PLGA nanoparticles. Pharmazie, 72(9), 525-528. doi:10.1691/ph.2017.7015 Thun, M. J., Henley, S. J., & Patrono, C. (2002). Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues. J Natl Cancer Inst, 94(4), 252-266. doi:10.1093/jnci/94.4.252 Thun, M. J., Henley, S. J., & Patrono, C. (2002). Nonsteroidal Anti-inflammatory Drugs as Anticancer Agents: Mechanistic, Pharmacologic, and Clinical Issues. Journal of the National Cancer Institute, 94(4), 252-266. doi:10.1093/jnci/94.4.252 Warsi, M. H., Anwar, M., Garg, V., Jain, G. K., Talegaonkar, S., Ahmad, F. J., & Khar, R. K. (2014). Dorzolamide-loaded PLGA/vitamin E TPGS nanoparticles for glaucoma therapy: Pharmacoscintigraphy study and evaluation of extended ocular hypotensive effect in rabbits. Colloids and Surfaces B: Biointerfaces, 122, 423-431. doi:https://doi.org/10.1016/j.colsurfb.2014.07.004 Wicki, A., Witzigmann, D., Balasubramanian, V., & Huwyler, J. (2015). Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications. J Control Release, 200, 138-157. doi:10.1016/j.jconrel.2014.12.030 Win, K. Y., & Feng, S.-S. (2006). In vitro and in vivo studies on vitamin E TPGS-emulsified poly(d,l-lactic-co-glycolic acid) nanoparticles for paclitaxel formulation. Biomaterials, 27(10), 2285-2291. doi:https://doi.org/10.1016/j.biomaterials.2005.11.008 Yang, C., Wu, T., Qi, Y., & Zhang, Z. (2018). Recent Advances in the Application of Vitamin E TPGS for Drug Delivery. Theranostics, 8(2), 464-485. doi:10.7150/thno.22711 Yerlikaya, F., Ozgen, A., Vural, I., Guven, O., Karaagaoglu, E., Khan, M. A., & Capan, Y. (2013). Development and evaluation of paclitaxel nanoparticles using a quality-by-design approach. J Pharm Sci, 102(10), 3748-3761. doi:10.1002/jps.23686 Yerlikaya, F., Ozgen, A., Vural, I., Guven, O., Karaagaoglu, E., Khan, M. A., & Capan, Y. (2013). Development and Evaluation of Paclitaxel Nanoparticles Using a Quality-by-Design Approach. Journal of Pharmaceutical Sciences, 102(10), 3748-3761. doi:https://doi.org/10.1002/jps.23686 Yu, L. X., Amidon, G., Khan, M. A., Hoag, S. W., Polli, J., Raju, G. K., & Woodcock, J. (2014). Understanding pharmaceutical quality by design. The AAPS journal, 16(4), 771-783. doi:10.1208/s12248-014-9598-3 Zhang, Z., Tan, S., & Feng, S.-S. (2012). Vitamin E TPGS as a molecular biomaterial for drug delivery. Biomaterials, 33(19), 4889-4906. doi:http://dx.doi.org/10.1016/j.biomaterials.2012.03.046 Zhu, H., Chen, H., Zeng, X., Wang, Z., Zhang, X., Wu, Y., . . . Feng, S.-S. (2014). Co-delivery of chemotherapeutic drugs with vitamin E TPGS by porous PLGA nanoparticles for enhanced chemotherapy against multi-drug resistance. Biomaterials, 35(7), 2391-2400. doi:https://doi.org/10.1016/j.biomaterials.2013.11.086