title: Tumor delivery of liposomal doxorubicin prepared with poly-L-glutamic acid as a drug-trapping agent.
abstract: BACKGROUND
  Poly-l-glutamic acid (PGA) is an anionic polymer with a large number of carboxyl groups that can interact electrostatically with cationic drugs such as doxorubicin (DOX).
  
  
  OBJECTIVE
  For stable encapsulation of DOX into liposomes, we prepared triethylamine (TEA)-PGA-liposomes using PGA as an internal trapping agent.
  
  
  METHODS
  We prepared TEA-PGA-liposomes by remote loading of DOX with a TEA gradient into preformed liposomes prepared with 1, 2, or 4 mg/mL PGA (molecular weights 4800, 9800, and 20 500), and evaluated their biodistribution and antitumor effects on Lewis lung carcinoma (LLC) tumor-bearing mice.
  
  
  RESULTS
  TEA-PGA-liposomes using the higher the molecular weight or concentration of PGA showed a slower release of DOX from the liposomes. TEA-PGA-liposomes prepared with a high concentration of PGA could enhance DOX accumulation in tumors and prolonged DOX circulation in the serum, indicating that DOX may be retained stably in the liposomal interior by interaction with PGA. Furthermore, injection of TEA-PGA-liposomes prepared with 4 mg/mL of PGA9800or 2 mg/mL PGA20500strongly inhibited tumor growth in LLC tumor-bearing mice.
  
  
  CONCLUSIONS
  PGA may be a potential trapping agent for liposomal DOX for tumor drug delivery.
authors.affiliation: a Department of Drug Delivery Research and.
authors.forename: Andang
authors.initials: A
authors.lastname: Miatmoko
authors.affiliation: a Department of Drug Delivery Research and.
authors.forename: Kumi
authors.initials: K
authors.lastname: Kawano
authors.affiliation: a Department of Drug Delivery Research and.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Yoda
authors.affiliation: b Department of Physical Chemistry , Hoshi University , Ebara , Shinagawa , Tokyo , Japan.
authors.forename: Etsuo
authors.initials: E
authors.lastname: Yonemochi
authors.affiliation: a Department of Drug Delivery Research and.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hattori
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D005021:Ethylamines / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D008081:Liposomes / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D011099:Polyglutamic Acid / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D005021:Ethylamines; D008081:Liposomes; D011099:Polyglutamic Acid; D004317:Doxorubicin; C016162:triethylamine
keywords: Doxorubicin; Poly-l-glutamic acid; liposome; trapping agent; tumor