Erlotinib entrapped in cholesterol-depleting cyclodextrin nanoparticles shows improved antitumoral efficacy in 3D spheroid tumors of the lung and the liver

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Varan G., Demirturk N., Benito J. M., BİLENSOY E.

Journal of Drug Targeting, cilt.29, sa.4, ss.439-453, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 29 Sayı: 4
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1080/1061186x.2020.1853743
  • Dergi Adı: Journal of Drug Targeting
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Chemical Abstracts Core, EMBASE, International Pharmaceutical Abstracts, MEDLINE
  • Sayfa Sayıları: ss.439-453
  • Anahtar Kelimeler: 3D multicellular spheroid, amphiphilic cyclodextrin, cholesterol, erlotinib, nanoparticle, hepatocellular carcinoma, non-small cell lung carcinoma, DRUG-DELIVERY, IN-VITRO, PHYSICOCHEMICAL PROPERTIES, ANTICANCER, NANOCAPSULES, SYSTEMS, DESIGN
  • Hacettepe Üniversitesi Adresli: Evet

Özet

© 2020 Informa UK Limited, trading as Taylor & Francis Group.Erlotinib (ERL), a tyrosine kinase inhibitor approved for therapeutic use in non-small cell lung cancer is further researched for eventual liver cancer treatment. However, conventional ERL has important bioavailability problems resulting from oral administration, poor solubility and gastrointestinal degradation into inactive metabolites. Alternative administration routes and nanoparticulate drug delivery systems are studied to prevent or reduce these drawbacks. In this study, ERL-loaded CD nanosphere and nanocapsule formulations capable of cholesterol depletion in resistant cancer cells were evaluated for ERL delivery. Drug loading and release profile depended largely on the surface charge of nanoparticles. Antiproliferative activity data obtained from 2D and 3D cell culture models demonstrated that polycationic βCD nanocapsules were the most effective formulation for ERL delivery to lung and liver cancer cells. 3D tumour tumoral penetration studies further revealed that nanocapsule formulations penetrated deeper into the tumour through the multilayered cells. Furthermore, all formulations were able to extract membrane cholesterol from lung and liver cancer cell lines, indicating the induction of apoptosis and overcoming drug resistance. In conclusion, given their tumoral penetration and cell membrane cholesterol depletion abilities, amphiphilic CD nanocapsules emerge as promising alternatives to improve the safety and efficiency of ERL treatment of both liver and lung tumours.