We used nanoprecipitation to synthesise a
We used nanoprecipitation to synthesise a new PLGA NP loaded with PTX as an alternative means to improve the treatment of lung cancer. These biodegradable nanocarriers had a negative charge, a size below 250 nm and good biocompatibility even at the highest con-centration used. In vitro assays demonstrated a significant increase in PTX activity against lung cancer GW311616 in culture and an apoptosis in-crease in MTS derived from A549 and LL2 cells. What is more, PLGA-PTX NPs increased drug internalisation in these tumor cells and induced a greater antiproliferative activity against CSCs. In vivo, PLGA-PTX NPs accumulated a higher PTX concentration in lung and central nervous tissues than free PTX. Interestingly, low levels of PTX were detected in DRG. In any case, PLGA-PTX NPs induced a greater volume decrease (44.6%) than free PTX in immunocompetent C57BL/6 mice bearing subcutaneous LL2 tumors. Thus, our results suggest that PTX-loaded PLGA NPs could be suitable for intravenous administration as a new chemotherapy formulation that increases PTX activity and could reduce its side eﬀects. Although further assays are required to verify this hy-pothesis and to functionalise the PLGA NPs towards the lung tumor cells, the new nanocarriers have a significant potential for translation into clinical applications.
Conflict of interest
The authors declare no conflict of interest
This work was funded by Consejería de Salud de la Junta de Andalucía (projects P11-CTS-7649, PI-0476-2016 and PI-0102-2017) and by Granada University (project PP2015-13 and financial Groups 09/112016). This work was also partially supported by grant of Junta de Andalucía (PI-0038-2014). L.M.-B. is especially grateful for the fi-nancial support from V Plan Propio (University of Seville). The research grant (FPU) from Ministerio de Educación Cultura y Deporte (Government of Spain) and post-doctoral fellowship of the Erasmus
Mundus–PHOENIX Program awarded to MM El-Hammadi are ac-knowledged.
Appendix A. Supplementary data
M. Shibano, M. Taniguchi, K. Baba, M. Ju-ichi, Synergistic antitumor eﬀect of a combination of paclitaxel and carboplatin with nobiletin from Citrus depressa on non-small-cell lung cancer cell lines, Planta Med. 80 (2014) 452–457.
Y. Wei, Improving anti-tumor activity with polymeric micelles entrapping paclitaxel in pulmonary carcinoma, Nanoscale 4 (2012) 6004–6017.  A. Wicki, D. Witzigmann, V. Balasubramanian, J. Huwyler, Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications, J. Control. Release 200 (2015) 138–157.
 F. Sadat Tabatabaei Mirakabad, K. Nejati-Koshki, A. Akbarzadeh, M.R. Yamchi,
M. Milani, N. Zarghami, V. Zeighamian, A. Rahimzadeh, S. Alimohammadi,
I. Okamoto, et al., Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with ad-vanced non-small-cell lung cancer: final results of a phase III trial, J. Clin. Oncol. 30 (2012) 2055–2062.
S. Whiting, G. Oster, Cost eﬀectiveness of nab-paclitaxel plus carboplatin (nab-PC) relative to bevacizumab plus solvent-based paclitaxel and carboplatin (B+sb-PC) in elderly patients with advanced non-small cell lung cancer (NSCLC), Int. J. Radiat. Oncol. Biol. Phys. 90 (2014) S61–S62.
 Y. Yamashita, N. Egashira, K. Masuguchi, S. Ushio, T. Kawashiri, R. Oishi, Comparison of peripheral neuropathy induced by standard and nanoparticle
J. Jiménez-López et al.
 S. Koudelka, J. Turanek, Liposomal paclitaxel formulations, J. Control. Release 163 (2012) 322–334.  M. Slingerland, H.J. Guchelaar, H. Rosing, M.E. Scheulen, L.J. van Warmerdam, J.H. Beijnen, H. Gelderblom, Bioequivalence of Liposome-Entrapped Paclitaxel Easy-To-Use (LEP-ETU) formulation and paclitaxel in polyethoxylated castor oil: a randomized, two-period crossover study in patients with advanced cancer, Clin. Ther. 35 (2013) 1946–1954.