Oral docetaxel delivery with cationic polymeric core-shell nanocapsules: In vitro and in vivo evaluation

Daşkın D., Erdoğar N., İSKİT A. B., BİLENSOY E.

Journal of Drug Delivery Science and Technology, cilt.80, 2023 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 80
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1016/j.jddst.2023.104163
  • Dergi Adı: Journal of Drug Delivery Science and Technology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Biotechnology Research Abstracts, EMBASE
  • Anahtar Kelimeler: Docetaxel, Nanocapsule, Polycaprolactone, Gastrointestinal cancers, Oral chemotherapy
  • Hacettepe Üniversitesi Adresli: Evet

Özet

© 2023One of the most important drawbacks in chemotherapy is the lack of effective oral self-administration of chemotherapeutics due to low oral bioavailability and instability within the gastrointestinal tract, leading to systemic side effects. The main aim of this study was to develop Docetaxel (DCX) loaded polymeric nanocapsule formulations and evaluate in vitro and in vivo characteristics for local treatment of gastrointestinal cancers in comparison to DTX solution. Polycaprolactone (PCL) was the core polymer for the nanocapsules that were further coated with either polyethylene glycol (PEG) or chitosan (CS). Particle size remained within the range of 180–210 nm with a loading capacity of over 65%. Sustained release of DCX was observed within 24 h in gastrointestinal media. Cell culture studies revealed safety of blank nanocapsules. In addition, DCX nanocapsules were found to have significantly higher cytotoxicity than free DCX at the MCF-7 cell line (p < 0.05). Intestinal permeability of nanocapsulated DCX was increased 2-3-fold than free DCX. In vivo gastrointestinal uptake study in mice demonstrated that CS-PCL nanocapsules were significantly uptaken by gastric and intestinal tissues for an eventual local gastrointestinal cancer treatment.