Technologies For Targeting And Delivering Chemotherapeutics Directly To The Tumour Site

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Technologies For Targeting And Delivering Chemotherapeutics Directly To The Tumour Site

April 25, 2016 by David Orchard-Webb, PhD

Technologies For Targeting And Delivering Chemotherapeutics Directly To The Tumour Site

Curator: David Orchard-Webb, PhD

Chemotherapy is normally associated with debilitating side effects due to systemic toxicity to normal cells, however targeting the chemotherapeutics directly to the tumour should dramatically reduce these side effects. Several technologies designed to accomplish this are under development (Table 1).

Chemo-targeting-devices

Researchers of the NTU-Northwestern Institute of Nanomedicine at Nanyang Technological University in Singapore are developing magnetic microbubbles which can contain chemotherapeutics. The microbubbles can be systemically delivered and imaged in real time. The chemotherapeutic is released from the microbubbles at the tumour site by directing ultrasound at the location [1]. Therefore this technology has the potential to specifically deliver any chemotherapeutic to a desired tumour site in the body.

For more on nanoparticle delivery make sure to read the following pharmaceutical intelligence article concerning iCluster technology:

https://pharmaceuticalintelligence.com/2016/04/10/avoiding-chemotherapy-toxicities/

Researchers at PanTher Therapeutics are developing a novel drug-eluting device for targeting chemotherapeutics to solid tumours. The cremaphor formulation of paclitaxel has dose limiting toxicity which prevent its use for pancreatic cancer. Paclitaxel’s toxicity like the majority of chemotherapeutics stems from its systemic delivery and toxicity to normal cells. However recently an albumin-bound formulation (nab-paclitaxel) has demonstrated increased survival times in combination with gemcitabine compared to gemcitabine alone [2]. And now PanTher Therapeutics’ novel biodegradable device has been developed which can deliver chemotherapeutics including paclitaxel directly to the pancreas limiting systemic toxicities [3].

The device has been tested with paclitaxel and shown favourable results in mouse xenograft models over systemically delivered paclitaxel. The device is flexible and can be surgically placed over the pancreatic tumour where it rests delivering a steady flow of paclitaxel for the duration of the treatment. The one time insertion is an attractive aspect compared with repeated intravenous deliveries.

Researchers at PharmaCyte Biotech, Inc. are developing a cell encapsidation technology called Cell-in-a-Box® which protects the cells inside from the host immune system while allowing the free exchange of soluble proteins and chemicals. The chemotherapeutic ifosfamide is activated in the liver by cytochrome P450 enzymes and must travel systemically to the tumour site. The greater the distance of the tumour from the liver the greater the dose requirement for effective delivery. The toxicities induced by an effective dose for pancreatic cancer are too great. Using Cell-in-a-Box®, activated ifosfamide can however be targeted to the pancreatic cancer reducing the dose requirement.

Cell-in-a-Box® is made of polymers of cellulose sulphate [4]. Clinical studies have shown that it is possible to encapsulate 293 cells overexpressing cytochrome P450 and deliver the capsules to the pancreas via the blood vessels without adverse effects. Lower doses of ifosfamide can then be systemically delivered and yet have a high active local concentration at the pancreas. A phase II trial is planned to confirm effectiveness in pancreatic cancer patients refractory to gemcitabine and abraxane or FOLFIRINOX [5].

Researchers of the University of North Carolina at Chapel Hill have developed a new device based on inserting positive and negative electrodes on either side of a tumour, injecting a chemotherapeutic and then applying an electric field in order to drive the therapeutic into the tumour. This Iontophoresis device has been tested in pancreatic cancer mouse xenograft models with gemcitabine and the newer combination FOLFIRINOX. Significant tumour volume reductions compared to intravenous delivery of the chemotherapeutic were found in both cases [6, 7]. Clinical trials are planned in the near future [8].

REFERENCES

Gao, Yu, Chon U Chan, Qiushi Gu, Xudong Lin, Wencong Zhang, David Chen Loong Yeo, Astrid Marlies Alsema, et al. ‘Controlled Nanoparticle Release from Stable Magnetic Microbubble Oscillations’. NPG Asia Materials 8, no. 4 (8 April 2016): e260. doi:10.1038/am.2016.37.
Ma, W. W., and M. Hidalgo. ‘The Winning Formulation: The Development of Paclitaxel in Pancreatic Cancer’. Clinical Cancer Research 19, no. 20 (15 October 2013): 5572–79. doi:10.1158/1078-0432.CCR-13-1356.
Ligorio, Matteo, Laura Indolfi, David T. Ting, Kristina Xega, Nicola Aceto, Francesca Bersani, Cristina R. Ferrone, et al. ‘Abstract 4584: A Novel Drug-Eluting Platform for Localized Treatment of Pancreatic Cancer’. Cancer Research 74, no. 19 Supplement (10 January 2014): 4584–4584. doi:10.1158/1538-7445.AM2014-4584.
Gunzburg, W. H., and Brian Salmons. ‘Use of Cell Therapy as a Means of Targeting Chemotherapy to Inoperable Pancreatic Cancer’. ACTA BIOCHIMICA POLONICA-ENGLISH EDITION- 52, no. 3 (2005): 601. https://www.researchgate.net/profile/Brian_Salmons/publication/236627164_Cell_and_gene_therapy_to_improve_cancer_treatment/links/0deec52d89a7e213a2000000.pdf.
‘PharmaCyte Biotech Issues Update on Preparations for Its Pancreatic Cancer Clinical Trial Other OTC:PMCB’. Accessed 10 March 2016. https://globenewswire.com/news-release/2016/02/22/812825/0/en/PharmaCyte-Biotech-Issues-Update-on-Preparations-for-Its-Pancreatic-Cancer-Clinical-Trial.html.
Byrne, J. D., M. N. R. Jajja, A. T. O’Neill, L. R. Bickford, A. W. Keeler, N. Hyder, K. Wagner, et al. ‘Local Iontophoretic Administration of Cytotoxic Therapies to Solid Tumors’. Science Translational Medicine 7, no. 273 (4 February 2015): 273ra14–273ra14. doi:10.1126/scitranslmed.3009951.
Byrne, James D., Mohammad R. N. Jajja, Allison N. Schorzman, Amanda W. Keeler, J. Christopher Luft, William C. Zamboni, Joseph M. DeSimone, and Jen Jen Yeh. ‘Iontophoretic Device Delivery for the Localized Treatment of Pancreatic Ductal Adenocarcinoma’. Proceedings of the National Academy of Sciences 113, no. 8 (23 February 2016): 2200–2205. doi:10.1073/pnas.1600421113.
‘Early-Stage Drug Delivery Implant Targeting Pancreatic Cancer Tumors Showing Promise – FierceDrugDelivery’. Accessed 7 March 2016. http://www.fiercedrugdelivery.com/story/early-stage-drug-delivery-implant-targeting-pancreatic-cancer-tumors-showin/2016-02-16.