title: In vivo evaluation of poly-l-asparagine nanocapsules as carriers for anti-cancer drug delivery.
abstract: Here, we report the in vivo proof of-concept of a novel nanocarrier, poly-l-asparagine (PASN) nanocapsules, as an anticancer targeted drug delivery system. The nanocapsules were loaded with the fluorescent marker DiD (1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine perchlorate) and also with the model drug docetaxel to evaluate the biodistribution and efficacy profiles in healthy and glioma-bearing mice, respectively. Regardless of their cargo, the nanocapsules presented a size close to 180 nm, a surface charge around -40 mV and an encapsulation efficiency of 75-90%. The biodistribution study in healthy mice showed that PASN nanocapsules led to a two- and three-fold increment in the mean residence time (MRT) and area under the curve (AUC) values, respectively, compared to those of a non-polymeric nanoemulsion. Finally, the efficacy/toxicity study indicated that the encapsulated drug was as efficacious as the commercial formulation (Taxotere(®)), with the additional advantage of being considerably less toxic. Overall, these results suggest the potential of PASN nanocapsules as drug nanocarriers in anticancer therapy.
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Campus Vida, University of Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain; Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Campus Vida, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Gustavo R
authors.initials: GR
authors.lastname: Rivera-Rodriguez
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lollo
authors.forename: Tristan
authors.initials: T
authors.lastname: Montier
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Benoit
authors.forename: Catherine
authors.initials: C
authors.lastname: Passirani
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Alonso
authors.forename: Dolores
authors.initials: D
authors.lastname: Torres
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D001216:Asparagine / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D000077143:Docetaxel; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005910:Glioma / Q000188:drug therapy; D051379:Mice; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D043823:Taxoids / Q000008:administration & dosage; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D053769:Nanocapsules; D043823:Taxoids; D000077143:Docetaxel; D001216:Asparagine
keywords: Cancer therapy; Docetaxel; Nanocapsules; Poly-l-asparagine; Polyaminoacids; Tumor targeting