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

• Published in: Journal of controlled release 2013-07, Vol.169 (1-2), p.10-16
• Main Authors: Gonzalo, Teresa, Lollo, Giovanna, Garcia-Fuentes, Marcos, Torres, Dolores, Correa, Juan, Riguera, Ricardo, Fernandez-Megia, Eduardo, Calvo, Pilar, Avilés, Pablo, Guillén, Maria José, Alonso, Maria José
• Format: Article
• Language: English
• Subjects: Animals; antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; biodegradability; blood circulation; Cancer; Depsipeptides - administration & dosage; Depsipeptides - pharmacokinetics; encapsulation; freeze drying; Long-circulating nanocarriers; Male; Mice; Models, Molecular; Nanocapsules; Nanocapsules - chemistry; Nanocapsules - toxicity; nanocarriers; Nanomedicines; pharmacokinetics; Polyglutamic acid; Polyglutamic Acid - chemistry; Polyglutamic Acid - toxicity; solvents; toxicity; zeta potential
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2013.03.037

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 200nm, 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 therapy. [Display omitted]