Gonzalo, TeresaLollo, GiovannaGarcía-Fuentes, MarcosTorres, DoloresCorrea, JuanRiguera Vega, RicardoFernández Megía, EduardoCalvo, PilarAvilés, PabloGuillén, Maria JoséAlonso Fernández, María José2018-07-062018-07-062013-07Gonzalo, T., Lollo, G., Garcia-Fuentes, M., Torres, D., Correa, J., & Riguera, R. et al. (2013). A new potential nano-oncological therapy based on polyamino acid nanocapsules. Journal Of Controlled Release, 169(1-2), 10-16. doi: 10.1016/j.jconrel.2013.03.0370168-3659http://hdl.handle.net/10347/16975A critical objective in cancer therapy is to reduce the systemic toxicity through the modification of the biodistribution of anticancer drugs. Herein, we disclose a new biodegradable nanocarrier, polyglutamic acid (PGA) nanocapsules, and present the in vivo pharmacokinetics/toxicity proof-of-concept for the anticancer drug plitidepsin. These novel nanocapsules were prepared using a modified solvent displacement technique where the polyamino acid was electrostatically deposited onto the lipid core. The nanocapsules exhibited an average size of 200 nm, a negative zeta potential and a great capacity for the encapsulation of plitidepsin (encapsulation efficiency above 90%). In addition, the nanocapsules could be freeze-dried and showed an adequate stability profile upon storage. Finally, the in vivo proof-of-concept studies performed in mice indicated that the encapsulation provided the drug with a prolonged blood circulation and a significantly reduced toxicity. In fact, the maximum tolerated dose of the nanoencapsulated drug was more than 3 times that of the reference formulation (Cremophor® EL plitidepsin solution). Overall, beyond the value of this specific formulation, the work reported here represents the evidence of the potential of polyamino acid nanocapsules in nano-oncological therapyeng© 2013 Elsevier B.V. This manuscript version is made available under the CC-BY-NC-ND 4.0 license (http:// creativecommons.org/licenses/by-nc-nd/4.0/)NanomedicinesLong-circulating nanocarriersNanocapsulesPolyglutamic acidCancerjournal article10.1016/j.jconrel.2013.03.037open access