Poly(allylamine) Magnetomicelles for Image Guided Drug Delivery

Barnett, Christopher M.; Lees, Martin R.; Curtis, A. D. M.; Lin, Paul Kong Thoo; Cheng, Wenguang; Hoskins, Clare

doi:10.2174/22117385113019990002

Cited by 7 publications

(16 citation statements)

References 42 publications

(65 reference statements)

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“…PAA-Ox5 was synthesized as previously reported [22]. PAA was reacted in 1:0.05 molar feed with 5-(4-chlorophenyl)-1,3,4-oxadiazole-2-thiol (oxadiazole, Ox) (monomer/pendant).…”

Section: Methodsmentioning

confidence: 99%

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Dual Acting Polymeric Nano-Aggregates for Liver Cancer Therapy

et al. 2018

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Liver cancer treatments are often hindered by poor drug physicochemical properties, hence there is a need for improvement in order to increase patient survival and outlook. Combination therapies have been studied in order to evaluate whether increased overall efficacy can be achieved. This study reports the combined treatment of liver cancer cells with a combination treatment of chemotherapeutic agent paclitaxel and pro-apoptotic protein cytochrome C. In order to administer both agents in a single formulation, a poly(allylamine)-based amphiphile has been fabricated with the incorporation of a hybrid iron oxide-gold nanoparticle into its structure. Here, the insoluble paclitaxel becomes incorporated into the hydrophobic core of the self-assemblies formed in an aqueous environment (256 nm), while the cytochrome C attaches irreversibly onto the hybrid nanoparticle surface via gold-thiol dative covalent binding. The self-assemblies were capable of solubilising up to 0.698 mg/mL of paclitaxel (700-fold improvement) with 0.012 mg/mL of cytochrome C also attached onto the hybrid iron oxide-gold nanoparticles (HNPs) within the hydrophobic core. The formulation was tested on a panel of liver cancer cells and cytotoxicity was measured. The findings suggested that indeed a significant improvement in combined therapy (33-fold) was observed when compared with free drug, which was double the enhancement observed after polymer encapsulation without the cytochrome C in hepatocellular carcinoma (Huh-7D12) cells. Most excitingly, the polymeric nanoparticles did result in improved cellular toxicity in human endothelian liver cancer (SK-hep1) cells, which proved completely resistant to the free drug.

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“…PAA-Ox5 was synthesized as previously reported [22]. PAA was reacted in 1:0.05 molar feed with 5-(4-chlorophenyl)-1,3,4-oxadiazole-2-thiol (oxadiazole, Ox) (monomer/pendant).…”

Section: Methodsmentioning

confidence: 99%

“…This PAA-Ox5 construct has previously been reported as a magnetomicelle with the potential for drug solubilisation [22]. Unfortunately, the cytochrome C itself is freely water soluble and, hence, has no thermodynamic desire to become encapsulated inside the core of the self-assemblies formed.…”

Section: Introductionmentioning

confidence: 99%

Dual Acting Polymeric Nano-Aggregates for Liver Cancer Therapy

et al. 2018

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“…Using model drug molecules, we have shown that after either incorporation onto / into nanoparticles [19,20], or drug encapsulation into polymeric micelles [21], consistently increased drug uptake is achieved in vitro in pancreatic cancer cells. Additionally, in vivo in pancreatic xenograft models, we have shown that after delivery in a nanoparticle formulation, drug molecules are significantly more capable of tumor retardation compared with free drug molecules [14].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Diels Alder-mediated release of gemcitabine from hybrid nanoparticles for enhanced pancreatic cancer therapy

Oluwasanmi

Al-Shakarchi

Manzur

et al. 2017

Journal of Controlled Release

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Hybrid nanoparticles (HNPs) have shown huge potential as drug delivery vehicles for pancreatic cancer. Currently, the first line treatment, gemcitabine, is only effective in 23.8% of patients. To improve this, a thermally activated system was developed by introducing a linker between HNPs and gemcitabine. Whereby, heat generation resulting from laser irradiation of the HNPs promoted linker breakdown resulting in prodrug liberation. In vitro evaluation in pancreatic adenocarcinoma cells, showed the prodrug was 4.3 times less cytotoxic than gemcitabine, but exhibited 11-fold improvement in cellular uptake. Heat activation of the formulation led to a 56% rise in cytotoxicity causing it to outperform gemcitabine by 26%. In vivo the formulation outperformed free gemcitabine with a 62% reduction in tumor weight in pancreatic xenografts. This HNP formulation is the first of its kind and has displayed superior anti-cancer activity as compared to the current first line drug gemcitabine after heat mediated controlled release.

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“…The phenomenon by which this passive targeting occurs is called the Enhanced Permeability and Retention (EPR) effect [21]. Studies have shown that once conjugated onto or into nanoparticles, drug molecules (or other cargo) exhibit greater cellular uptake [13,18,22]. Hence, a more rapid clinical effect can be achieved.…”

Section: Use Of Hnps As Drug Carriersmentioning

confidence: 99%

“…These include the development of magnetomicelles. Reports have successfully shown conjugation and potential of drug conjugated onto the surface of HNPs [22]. However, insoluble compounds are much more difficult to formulate onto their surface due to the potential to further decrease HNP stability resulting in precipitation.…”

Section: Incorporation Of Hnps Into Supramolecular Structuresmentioning

confidence: 99%