Publications

@article{Vasey2021-kq,

title = {Polymer pro-drug nanoparticles for sustained release of 

 cytotoxic drugs evaluated in patient-derived glioblastoma cell 

 lines and in situ gelling formulations},

author = {Catherine E Vasey and Robert J Cavanagh and Vincenzo Taresco and Cara Moloney and Stuart Smith and Ruman Rahman and Cameron Alexander},

year  = {2021},

date = {2021-02-01},

journal = {Pharmaceutics},

volume = {13},

number = {2},

pages = {208},

publisher = {MDPI AG},

abstract = {Glioblastoma (GBM) is the most common, malignant and aggressive 

 brain tumour in adults. Despite the use of multimodal 

 treatments, involving surgery, followed by concomitant 

 radiotherapy and chemotherapy, the median survival for patients 

 remains less than 15 months from diagnosis. Low penetration of 

 drugs across the blood-brain barrier (BBB) is a dose-limiting 

 factor for systemic GBM therapies, and as a result, 

 post-surgical intracranial drug delivery strategies are being 

 developed to ensure local delivery of drugs within the brain. 

 Here we describe the effects of PEGylated 

 poly(lactide)-poly(carbonate)-doxorubicin (DOX) nanoparticles 

 (NPs) on the metabolic activity of primary cancer cell lines 

 derived from adult patients following neurosurgical resection, 

 and the commercially available GBM cell line, U87. The results 

 showed that non-drug-loaded NPs were well tolerated at 

 concentrations of up to 100 µg/mL while tumour cell-killing 

 effects were observed for the DOX-NPs at the same 

 concentrations. Further experiments evaluated the release of DOX 

 from polymer-DOX conjugate NPs when incorporated in a 

 thermosensitive in situ gelling poly(DL-lactic-co-glycolic acid) 

 and poly(ethylene glycol) (PLGA/PEG) matrix paste, in order to 

 simulate the clinical setting of a locally injected formulation 

 for GBM following surgical tumour resection. These assays 

 demonstrated drug release from the polymer pro-drugs, when in 

 PLGA/PEG matrices of two formulations, over clinically relevant 

 time scales. These findings encourage future in vivo assessment 

 of the potential capability of polymer-drug conjugate NPs to 

 penetrate brain parenchyma efficaciously, when released from 

 existing interstitial delivery systems.},

keywords = {brain tumour, doxorubicin, local delivery, nanoparticles, polymer pro-drug},

pubstate = {published},

tppubtype = {article}

}