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}

}

@article{McCrorie2020-ag,

title = {Biomedical engineering approaches to enhance therapeutic 

 delivery for malignant glioma},

author = {Phoebe McCrorie and Catherine E Vasey and Stuart J Smith and Maria Marlow and Cameron Alexander and Ruman Rahman},

year  = {2020},

date = {2020-12-01},

journal = {J. Control. Release},

volume = {328},

pages = {917\textendash931},

publisher = {Elsevier BV},

abstract = {We review the challenges of next-generation therapeutics for 

 both systemic and localised delivery to brain tumours and 

 discuss how recent engineering advances may be used to enhance 

 brain penetration of systemic delivery therapies. The unmet 

 clinical need which drug delivery seeks to address is discussed 

 with reference to the therapy obstacles that the intra-tumour 

 heterogeneity of glioma present. The unmet chemistry and 

 biomedical engineering challenge to develop controlled release 

 therapeutics is appraised, with commentary on current 

 success/failures in systemic carrier-mediated delivery, 

 including receptor-targeted, cell-based, blood-brain-barrier 

 disrupting and MRI-guided focused ultrasound. Localised 

 therapeutic delivery is a relatively under-studied research 

 avenue and is discussed with reference to existing technologies 

 in preclinical development. These include convection-enhanced 

 delivery, alternative catheter delivery, and neuro-surgically 

 applied delivery systems such as polymeric hydrogels and 

 interstitial spray. A myriad of nano-scale therapeutic delivery 

 systems is emerging as potential future medicines for malignant 

 brain tumours. Such biomedically-engineered systems will 

 increasingly feature in next-generation neuro-oncological 

 clinical trials to deliver repurposed and experimental 

 therapeutics, aimed at achieving therapeutic drug concentrations 

 in the brain, with associated mortality and morbidity benefits 

 for patients.},

keywords = {blood-brain-barrier, brain tumour, Drug delivery, nanoparticles, Polymers, Receptor-targeting},

pubstate = {published},

tppubtype = {article}

}

@article{McCrorie2020-sx,

title = {Etoposide and olaparib polymer-coated nanoparticles within a 

 bioadhesive sprayable hydrogel for post-surgical localised 

 delivery to brain tumours},

author = {Phoebe McCrorie and Jatin Mistry and Vincenzo Taresco and Tatiana Lovato and Michael Fay and Ian Ward and Alison A Ritchie and Philip A Clarke and Stuart J Smith and Maria Marlow and Ruman Rahman},

year  = {2020},

date = {2020-12-01},

journal = {Eur. J. Pharm. Biopharm.},

volume = {157},

pages = {108\textendash120},

publisher = {Elsevier BV},

abstract = {Glioblastoma is a malignant brain tumour with a median survival 

 of 14.6 months from diagnosis. Despite maximal surgical 

 resection and concurrent chemoradiotherapy, reoccurrence is 

 inevitable. To try combating the disease at a stage of low 

 residual tumour burden immediately post-surgery, we propose a 

 localised drug delivery system comprising of a spray device, 

 bioadhesive hydrogel (pectin) and drug nanocrystals coated with 

 polylactic acid-polyethylene glycol (NCPPs), to be administered 

 directly into brain parenchyma adjacent to the surgical cavity. 

 We have repurposed pectin for use within the brain, showing in 

 vitro and in vivo biocompatibility, bio-adhesion to mammalian 

 brain and gelling at physiological brain calcium concentrations. 

 Etoposide and olaparib NCPPs with high drug loading have shown 

 in vitro stability and drug release over 120 h. Pluronic F127 

 stabilised NCPPs to ensure successful spraying, as determined by 

 dynamic light scattering and transmission electron microscopy. 

 Successful delivery of Cy5-labelled NCPPs was demonstrated in a 

 large ex vivo mammalian brain, with NCPP present in the tissue 

 surrounding the resection cavity. Our data collectively 

 demonstrates the pre-clinical development of a novel localised 

 delivery device based on a sprayable hydrogel containing 

 therapeutic NCPPs, amenable for translation to intracranial 

 surgical resection models for the treatment of malignant brain 

 tumours.},

keywords = {brain tumour, Etoposide, hydrogel, nanoparticles, Olaparib, Pectin, Spray},

pubstate = {published},

tppubtype = {article}

}