Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Κυριακή 2 Οκτωβρίου 2022

Neurosurgically-Applied Chemotherapy for Childhood Brain Tumours Arising in the Posterior Fossa Using a Biodegradable Paste

alexandrossfakianakis shared this article with you from Inoreader
Abstract
AIMS
This project aims to develop a local drug delivery system for treatment of childhood medulloblastoma (MB) and atypical teratoid/rhabdoid tumours (AT/RT), malignant brain neoplasms occurring in the posterior fossa for which prognoses remains poor. Our goal is to repurpose drug compounds reported as effective against MB and AT/RT, but which either cannot cross the blood-brain-barrier (BBB) or have not been assessed for localised delivery. We have developed a novel intra-cavity drug delivery system, consisting of polymer microparticles made from poly(DL-lactic-co-glycolic acid) and poly(ethylene glycol) (PLGA/PEG) which will be employed to release drugs over several weeks.
METHOD
Cell toxicity assays were undertaken using drugs of interest against an in vitro panel of relevant MB and AT/RT cell lines. PLGA/PEG paste incorporating the drugs were prepared and release kinetics assessed.
RESULTS
IC50 values of the drugs were assessed across all cell lines and a range of potencies were observed, with optimum conditions identified as dual treatments of PG545 (heparanse inhibitor) with CHIR99021 (glycogen synthase kinase-3 inhibitor) for MB and ribavirin (anti-viral) with CHIR99021 for AT/RT. Importantly, it was noted that the drugs retained their cytotoxicity following release from PLGA/PEG. Furthermore, release kinetics were finely tuned through careful control of the composition through addition of excipients and encapsulation of drugs in nanoparticles, and a library of formulations were prepared.
CONCLUSION
A local drug delivery system for MB and AT/RT has been developed and an optimum formulation, based upon in vitro cell assays and release kinetics, has been identified for in vivo efficacy studies in orthotopic models.
View on Web

Δεν υπάρχουν σχόλια:

Δημοσίευση σχολίου