Development, optimization and in vitro evaluation of oxaliplatin loaded nanoparticles in non-small cell lung cancer

Esim O., Bakirhan N. K., Yildirim N., Sarper M., Savaser A., Ozkan S. A., ...Daha Fazla

DARU, Journal of Pharmaceutical Sciences, cilt.28, sa.2, ss.673-684, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 28 Sayı: 2
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1007/s40199-020-00374-5
  • Dergi Adı: DARU, Journal of Pharmaceutical Sciences
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, CINAHL, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.673-684
  • Anahtar Kelimeler: Factorial design, Polycaprolactone, Nanoparticles, Oxaliplatin, Non-small cell lung cancer, In vitro, PLGA NANOPARTICLES, MOLECULAR-WEIGHT, FACTORIAL DESIGN, FORMULATION OPTIMIZATION, DELIVERY-SYSTEM, DRUG, RELEASE, SIZE, ENCAPSULATION, DEGRADATION
  • Ankara Üniversitesi Adresli: Evet

Özet

© 2020, Springer Nature Switzerland AG.Background: Platinum-based chemotherapy in non-small cell lung cancer (NSCLC) has been demonstrated as a promising approach by many researchers. However, due to low bioavailability and several side effects, drug targeting to lungs by intravenous administration is not a common route of administration. Objective: In this study, oxaliplatin loaded polycaprolactone (PCL) nanoparticles were prepared to overcome the limitations of the drug. 33 factorial design was used to evaluate the combined effect of the selected variables on the nanoparticle characteristics and to optimize oxaliplatin loaded PCL nanoparticles. Methods: The factorial design was used to study the influence of three different independent variables on the response of nanoparticle particle size, polydispersity index (PDI), zeta potential, and encapsulation efficiency. The cellular uptakes of oxaliplatin loaded nanoparticles with different molecular weights of PCL were evaluated. Moreover, optimized nanoparticles were evaluated for their efficacy in non-small lung cancer using the SK-MES-1 cell line. Results: In factorial design, it is found that the homogenization speed and surfactant ratio represented the main factors influencing particle size and PDI and did not seem to depend on the PCL ratio. While the cytotoxicity of free oxaliplatin and oxaliplatin loaded nanoparticles were similar in low drug doses (2.5 and 25 μg/mL), the cytotoxicity of oxaliplatin loaded nanoparticles on SK-MES-1 cell was found higher in higher doses (p < 0.05). Moreover, oxaliplatin nanoparticles formulated with different molecular weights of PCL did not show significant differences in cellular uptake in 1 h and 2 h. However, the uptake of PCL80000 NPs was found significantly greater than free oxaliplatin at 4 h (p < 0.05). Conclusion: Hence, the development of oxaliplatin loaded PCL nanoparticles can be a useful approach for effective NSCLC therapy. Graphical abstract: [Figure not available: see fulltext.]