A novel low molecular weight nanocomposite hydrogel formulation for intra-tumoural delivery of anti-cancer drugs

Štaka, Ivana; Cadete, Ana; Surikutchi, Bhanu Teja; Abuzaid, Haneen; Bradshaw, Tracey D.; Alonso, Maria J.; Marlow, Maria

Abstract

Herein, an injectable formulation composed of a low molecular weight gelator (LMWG) based hydrogel and drug-loaded polymeric nanocapsules (NCs) is described. The NCs, made of hyaluronic acid and polyglutamic acid and loaded with C14-Gemcitabine (GEM C14), showed a size of 40 and 80 nm and a encapsulation efficiency > 90%. These NCs exhibited a capacity to control the release of the encapsulated drug for more than 1 month. GEM C14-loaded NCs showed activity against various cancer cell lines in vitro; cell growth inhibition by 50% (GI50) values of 15 ± 6, 10 ± 9, 13 ± 3 and 410 ± 463 nM were obtained in HCT 116, MIA PaCa-2, Panc-1 and Panc-1 GEM resistant cell lines respectively. Nanocomposite hydrogels were prepared using the LMWG - N4-octanoyl-2’-deoxycytidine and loaded for the first time with polymeric NCs. 2% and 4% w/v nanocapsule concentrations as compared to 8% w/v NC concentrations with 2 % and 3% w/v gelator concentrations gave mechanically stronger gels as determined by oscillatory rheology. Most importantly, the nanocomposite formulation reformed instantly into a gel after injection through a needle. Based on these properties, the nanocomposite gel formulation has potential for the intratumoural delivery of anticancer drugs.

Citation

Štaka, I., Cadete, A., Surikutchi, B. T., Abuzaid, H., Bradshaw, T. D., Alonso, M. J., & Marlow, M. (2019). A novel low molecular weight nanocomposite hydrogel formulation for intra-tumoural delivery of anti-cancer drugs. International Journal of Pharmaceutics, 565, 151-161. https://doi.org/10.1016/j.ijpharm.2019.04.070

• Journal Article Type: Article
• Acceptance Date: Apr 24, 2019
• Online Publication Date: Apr 25, 2019
• Publication Date: Jun 30, 2019
• Deposit Date: May 8, 2019
• Publicly Available Date: Apr 26, 2020
• Journal: International Journal of Pharmaceutics
• Print ISSN: 0378-5173
• Electronic ISSN: 1873-3476
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 565
• Pages: 151-161
• DOI: https://doi.org/10.1016/j.ijpharm.2019.04.070
• Keywords: Gel-nanocomposite; Polymeric nanocapsules; Low molecular weight gelators; Local delivery
• Public URL: https://nottingham-repository.worktribe.com/output/1872983
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0378517319303400
• Additional Information: This work was supported by the European Commission, Education, Audiovisual and Culture Executive Agency (EACEA), Erasmus Mundus programme, NanoFar doctorate funding.