Etoposide and olaparib polymer-coated nanoparticles within a bioadhesive sprayable hydrogel for post-surgical localised delivery to brain tumours

McCrorie, Phoebe; Mistry, J.; Taresco, Vincenzo; Lovato, Tatiana; Fay, Michael W.; Ward, Ian; Ritchie, Alison; Clarke, Philip; Smith, Stuart; Marlow, Maria; Rahman, Ruman

doi:10.1016/j.ejpb.2020.10.005

Cited by 45 publications

(24 citation statements)

References 78 publications

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“…DOX-loaded acetylated dextran nanofibrous scaffolds were designed with different degradability rates, leading to complete remission in 43% of mice orthotopically challenged with U87-MG cells [16]. Rahman and colleagues engineered a hydrogel composed of low-methoxyl pectin encapsulating etoposide or olaparib drug nanocrystals coated with polylactic acid-polyethylene glycol; delivery as a spray showed deeper brain penetration [17]. However, despite the recent interesting achievements, most of the nanocarriers described so far suffer from poor translation to the clinic due to low biodegradability, potential neurotoxicity, poor drug loading, and inadequate drug release kinetics, which prevent the drug from reaching the peripheral GBM [6,18].…”

Section: Introductionmentioning

confidence: 99%

Design of Bio-Responsive Hyaluronic Acid–Doxorubicin Conjugates for the Local Treatment of Glioblastoma

Malfanti¹,

Catania²,

Degros³

et al. 2022

Pharmaceutics

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Glioblastoma is an unmet clinical need. Local treatment strategies offer advantages, such as the possibility to bypass the blood–brain barrier, achieving high drug concentrations at the glioblastoma site, and consequently reducing systemic toxicity. In this study, we evaluated the feasibility of using hyaluronic acid (HA) for the local treatment of glioblastoma. HA was conjugated to doxorubicin (DOX) with distinct bio-responsive linkers (direct amide conjugation HA-NH-DOX), direct hydrazone conjugation (HA-Hz-DOX), and adipic hydrazone (HA-AdpHz-DOX). All HA-DOX conjugates displayed a small size (less than 30 nm), suitable for brain diffusion. HA-Hz-DOX showed the best performance in killing GBM cells in both 2D and 3D in vitro models and displayed superior activity in a subcutaneous GL261 tumor model in vivo compared to free DOX and other HA-DOX conjugates. Altogether, these results demonstrate the feasibility of HA as a polymeric platform for the local treatment of glioblastoma and the importance of rationally designing conjugates.

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Section: Introductionmentioning

confidence: 99%

Design of Bio-Responsive Hyaluronic Acid–Doxorubicin Conjugates for the Local Treatment of Glioblastoma

Malfanti¹,

Catania²,

Degros³

et al. 2022

Pharmaceutics

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“…The nanoparticles had aggregated in the brain according to fluorescent imaging results. A pharmacological platform for malignant brain cancers was introduced by the sprayable hydrogel ( McCrorie et al, 2020 ). These simplistic but novel strategic approaches can boost the activity of PARP inhibitors.…”

Section: Strategiesmentioning

confidence: 99%

Role of PARP Inhibitors in Glioblastoma and Perceiving Challenges as Well as Strategies for Successful Clinical Development

et al. 2022

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Glioblastoma multiform is the most aggressive primary type of brain tumor, representing 54% of all gliomas. The average life span for glioblastoma multiform is around 14–15 months instead of treatment. The current treatment for glioblastoma multiform includes surgical removal of the tumor followed by radiation therapy and temozolomide chemotherapy for 6.5 months, followed by another 6 months of maintenance therapy with temozolomide chemotherapy (5 days every month). However, resistance to temozolomide is frequently one of the limiting factors in effective treatment. Poly (ADP-ribose) polymerase (PARP) inhibitors have recently been investigated as sensitizing drugs to enhance temozolomide potency. However, clinical use of PARP inhibitors in glioblastoma multiform is difficult due to a number of factors such as limited blood–brain barrier penetration of PARP inhibitors, inducing resistance due to frequent use of PARP inhibitors, and overlapping hematologic toxicities of PARP inhibitors when co-administered with glioblastoma multiform standard treatment (radiation therapy and temozolomide). This review elucidates the role of PARP inhibitors in temozolomide resistance, multiple factors that make development of these PARP inhibitor drugs challenging, and the strategies such as the development of targeted drug therapies and combination therapy to combat the resistance of PARP inhibitors that can be adopted to overcome these challenges.

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“…The drug was released over the time of 120 h. The fluorescent imaging revealed that the NPs were accumulated in the mammalian brain. The sprayable hydrogel presented a novel therapeutic platform for malignant brain tumors [ 113 ]. Figure 2 represents the process of delivering a PARP inhibitor to glioblastoma cells using a bioadhesive sprayable gel.…”

Section: Nanoformulations For Delivery Of Parp Inhibitors To Cancer Cellsmentioning

confidence: 99%

Active Targeted Nanoparticles for Delivery of Poly(ADP-ribose) Polymerase (PARP) Inhibitors: A Preliminary Review

Sargazi¹,

Mukhtar

Rahdar

et al. 2021

IJMS

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Nanotechnology has revolutionized novel drug delivery strategies through establishing nanoscale drug carriers, such as niosomes, liposomes, nanomicelles, dendrimers, polymeric micelles, and nanoparticles (NPs). Owing to their desirable cancer-targeting efficacy and controlled release, these nanotherapeutic modalities are broadly used in clinics to improve the efficacy of small-molecule inhibitors. Poly(ADP-ribose) polymerase (PARP) family members engage in various intracellular processes, including DNA repair, gene transcription, signal transduction, cell cycle regulation, cell division, and antioxidant response. PARP inhibitors are synthetic small-molecules that have emerged as one of the most successful innovative strategies for targeted therapy in cancer cells harboring mutations in DNA repair genes. Despite these advances, drug resistance and unwanted side effects are two significant drawbacks to using PARP inhibitors in the clinic. Recently, the development of practical nanotechnology-based drug delivery systems has tremendously improved the efficacy of PARP inhibitors. NPs can specifically accumulate in the leaky vasculature of the tumor and cancer cells and release the chemotherapeutic moiety in the tumor microenvironment. On the contrary, NPs are usually unable to permeate across the body’s normal organs and tissues; hence the toxicity is zero to none. NPs can modify the release of encapsulated drugs based on the composition of the coating substance. Delivering PARP inhibitors without modulation often leads to the toxic effect; therefore, a delivery vehicle is essential to encapsulate them. Various nanocarriers have been exploited to deliver PARP inhibitors in different cancers. Through this review, we hope to cast light on the most innovative advances in applying PARP inhibitors for therapeutic purposes.

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Etoposide and olaparib polymer-coated nanoparticles within a bioadhesive sprayable hydrogel for post-surgical localised delivery to brain tumours

Cited by 45 publications

References 78 publications

Design of Bio-Responsive Hyaluronic Acid–Doxorubicin Conjugates for the Local Treatment of Glioblastoma

Design of Bio-Responsive Hyaluronic Acid–Doxorubicin Conjugates for the Local Treatment of Glioblastoma

Role of PARP Inhibitors in Glioblastoma and Perceiving Challenges as Well as Strategies for Successful Clinical Development

Active Targeted Nanoparticles for Delivery of Poly(ADP-ribose) Polymerase (PARP) Inhibitors: A Preliminary Review

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