title: A new potential nano-oncological therapy based on polyamino acid nanocapsules.
abstract: 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 therapy.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy, Campus Vida, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Gonzalo
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lollo
authors.forename: Marcos
authors.initials: M
authors.lastname: Garcia-Fuentes
authors.forename: Dolores
authors.initials: D
authors.lastname: Torres
authors.forename: Juan
authors.initials: J
authors.lastname: Correa
authors.forename: Ricardo
authors.initials: R
authors.lastname: Riguera
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fernandez-Megia
authors.forename: Pilar
authors.initials: P
authors.lastname: Calvo
authors.forename: Pablo
authors.initials: P
authors.lastname: Avilés
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Guillén
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Alonso
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D047630:Depsipeptides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008958:Models, Molecular; D053769:Nanocapsules / Q000737:chemistry* / Q000633:toxicity; D010456:Peptides, Cyclic; D011099:Polyglutamic Acid / Q000737:chemistry* / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D047630:Depsipeptides; D053769:Nanocapsules; D010456:Peptides, Cyclic; D011099:Polyglutamic Acid; C098980:plitidepsin