New generation of drug-loaded lipid nanocapsule hydrogel : a sustained and specific drug delivery system against glioblastoma

• Κύριος συγγραφέας: Farooq, Umer
• Άλλοι συγγραφείς: Αντιμησιάρη, Σοφία
• Μορφή: Thesis
• Γλώσσα: English
• Έκδοση: 2020
• Θέματα: Glioblastoma; Hydrogels; Lipids nanocapsules; Chemotherapy; Γλοιοβλάστωμα; Υδρογέλες; Νανοκάψουλες λιπιδίων; Χημειοθεραπεία

Glioblastoma (GBM) is a malignant brain tumor which results in high mortality. The current standard of care consists of surgical resection combined with adjuvant radiotherapy and/or chemotherapy. But due to recurrences from residual infiltrated GBM cells at the border of resection, the median survival is very low: 14 months with 5-year survival rate lower than 10%. We developed an implantable lipid nanocapsule (LNC)-based hydrogel without polymer, which will bridge the current therapeutic gap between surgical resection and initiation of systemic treatment. This hydrogel is expected to limit GBM recurrences by i) maintaining therapeutic concentrations of anticancer drugs at the resection border (without the necessity of crossing the blood-brain barrier) and ii) targeting GBM cells specifically using NFL-TBS.40-63 (NFL) targeting peptide. This traineeship focused on the optimization of NFL peptide adsorption at the surface of LNCs in suspension and in gel form, using surface-modified LNCs. Total adsorption of NFL was obtained with negatively charged LNCs, without modifying the mechanical property of the gel. The targeting property of the NFL peptide was maintained, observed by a higher internalization of NFL-adsorbed LNCs in F98 (GBM) cell line in comparison to non-modified LNCs, after gel dissolution. Next step will be the confirmation of a higher therapeutic efficacy (cytotoxicity assay) using drug loaded LNCs in the gel form.