title: The in vivo behavior and antitumor activity of doxorubicin-loaded poly(γ-benzyl l-glutamate)-block-hyaluronan polymersomes in Ehrlich ascites tumor-bearing BalB/c mice.
abstract: The in vivo efficacy of doxorubicin (DOX)-loaded poly(γ-benzyl l-glutamate)-block-hyaluronan (PBLG(23)-b-HYA(10))-based polymersomes (PolyDOX) was evaluated. Samples were efficiently labeled with technetium-99m radionuclide with good stability for in vivo studies. PolyDOX enhanced circulation time compared to free DOX. Biodistribution studies revealed selective accumulation of PolyDOX in the Ehrlich ascites tumor (EAT) as a result of passive accumulation and active targeting (CD44-mediated endocytosis) in EAT-bearing mice. Toxicity studies demonstrated PolyDOX is a safe drug carrier, and no hemolysis was observed with PolyDOX equivalent to 200 μg/mL of free DOX. PolyDOX dominantly controlled tumor growth by delaying doubling time of EATs compared to free DOX over 30 days after treatment. PolyDOX also increased life span six times more than free DOX. Hence, it is reasonable to expect that higher DOX levels attributable to PolyDOX improve the therapeutic index and reduce side effects due to site-specific drug accumulation.
  
  
  BACKGROUND
  In this preclinical project, doxorubicin loaded polymersomes enhanced intracellular uptake of doxorubicin in a murine model of Ehrlich Ascites Tumor (EAT) through CD44 receptor mediated endocytosis, resulting in prolonged Tumor Doubling Time and increase in life span of mice.
authors.affiliation: Université de Bordeaux, Pessac-Cedex, France.
authors.forename: Kamal Kumar
authors.initials: KK
authors.lastname: Upadhyay
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Mishra
authors.forename: Krishna
authors.initials: K
authors.lastname: Chuttani
authors.forename: Ankur
authors.initials: A
authors.lastname: Kaul
authors.forename: Christophe
authors.initials: C
authors.lastname: Schatz
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Le Meins
authors.forename: Ambikanandan
authors.initials: A
authors.lastname: Misra
authors.forename: Sebastien
authors.initials: S
authors.lastname: Lecommandoux
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000138:chemical synthesis* / Q000627:therapeutic use; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000138:chemical synthesis* / Q000627:therapeutic use; D004337:Drug Carriers / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D004705:Endocytosis / Q000276:immunology; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology*; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011099:Polyglutamic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000627:therapeutic use; D011817:Rabbits; D013667:Technetium / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D018960:Hyaluronan Receptors; C549034:poly(gamma-benzyl glutamate)-b-hyaluronan; D011099:Polyglutamic Acid; D013667:Technetium; D004317:Doxorubicin; D006820:Hyaluronic Acid