A new potential nano-oncological therapy based on polyamino acid nanocapsules

A 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 therapyThe authors would like to acknowledge financial support from CENIT-NANOFAR XS53 project, PharmaMar, Spain, the Ministry of Sciences and Innovation ((CTQ2009-10963), the Xunta de Galicia (Competitive Reference Groups-FEDER funds Ref. 2010/18, and CN2011/037) and the European Commission FP7 EraNet — EuroNanoMed Program-Instituto Carlos III (Lymphotarg proyect, Ref. PS09/02670). Giovanna Lollo has a fellowship from the Ministry of Education of Spain. Marcos Garcia Fuentes acknowledges an Isidro Parga Pondal Fellowship from Xunta de GaliciaS