title: Enhanced in vivo therapeutic efficacy of plitidepsin-loaded nanocapsules decorated with a new poly-aminoacid-PEG derivative.
abstract: The focus of this study is to disclose a new delivery carrier intended to improve the pharmacokinetic characteristics of the anticancer drug plitidepsin and to favor its accumulation within the tumor. These nanocarriers named as nanocapsules, consist of an oily core surrounded by a highly PEGylated polyglutamic acid (PGA-PEG) shell loaded with plitidepsin. They showed a size of around 190 nm, a zeta potential of -24 mV and were able to encapsulate a high percentage (85%) of plitidepsin. In vivo studies, following intravenous injection in healthy mice, indicated that the encapsulation of the drug within PGA-PEG nanocapsules led to an important increase in its area under the curve (AUC) which is related to the important decrease of the clearance, as compared to the values observed for the drug dissolved in a Cremophor(®) EL solution. This improvement of the pharmacokinetic profile of the encapsulated plitidepsin was accompanied by a high increase (2.5-fold) of the maximum tolerated dose (MTD) in comparison to that of plitidepsin Cremophor(®) EL solution. The efficacy study performed in a xenograft tumor mice model evidenced the capacity of PGA-PEG nanocapsules to significantly reduce tumor growth. These promising results highlight the potential of PGA-PEG nanocapsules as an effective drug delivery system for cancer therapy.
authors: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Campus Vida, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy and Heath Research Institute of Santiago de Compostela (IDIS), Campus Vida, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors: Giovanna
authors: G
authors: Lollo
authors: Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy and Heath Research Institute of Santiago de Compostela (IDIS), Campus Vida, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors: Pablo
authors: P
authors: Hervella
authors: PharmaMar S.A, Colmenar Viejo, Madrid, Spain.
authors: Pilar
authors: P
authors: Calvo
authors: PharmaMar S.A, Colmenar Viejo, Madrid, Spain.
authors: Pablo
authors: P
authors: Avilés
authors: PharmaMar S.A, Colmenar Viejo, Madrid, Spain.
authors: Maria Jose
authors: MJ
authors: Guillén
authors: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Campus Vida, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy and Heath Research Institute of Santiago de Compostela (IDIS), Campus Vida, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors: Marcos
authors: M
authors: Garcia-Fuentes
authors: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Campus Vida, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy and Heath Research Institute of Santiago de Compostela (IDIS), Campus Vida, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors: Maria José
authors: MJ
authors: Alonso
authors: Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy and Heath Research Institute of Santiago de Compostela (IDIS), Campus Vida, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain. Electronic address: dolores.torres@usc.es.
authors: Dolores
authors: D
authors: Torres
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D047630:Depsipeptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D051379:Mice; D008819:Mice, Nude; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D010316:Particle Size; D010456:Peptides, Cyclic; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000008:administration & dosage / Q000737:chemistry*; D013499:Surface Properties; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D047630:Depsipeptides; D004337:Drug Carriers; D053769:Nanocapsules; D010456:Peptides, Cyclic; D011099:Polyglutamic Acid; D011092:Polyethylene Glycols; C098980:plitidepsin
keywords: Antitumor drugs; Cancer therapy; Nanomedicine; Plitidepsin; Polyglutamic acid; Stealth properties