title: Porphyrin-phospholipid liposomes with tunable leakiness.
abstract: Drug bioavailability is a key consideration for drug delivery systems. When loaded with doxorubicin, liposomes containing 5 molar % porphyrin-phospholipid (HPPH liposomes) exhibited in vitro and in vivo serum stability that could be fine-tuned by varying the drug-to-lipid ratio. A higher drug loading ratio destabilized the liposomes, in contrast to standard liposomes which displayed an opposite and less pronounced trend. Following systemic administration of HPPH liposomes, near infrared laser irradiation induced vascular photodynamic damage, resulting in enhanced liposomal doxorubicin accumulation in tumors. In laser-irradiated tumors, the use of leaky HPPH liposomes resulted in improved doxorubicin bioavailability compared to stable standard liposomes. Using this approach, a single photo-treatment with 10mg/kg doxorubicin rapidly eradicated tumors in athymic nude mice bearing KB or MIA Paca-2 xenografts.
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260, USA.
authors.forename: Dandan
authors.initials: D
authors.lastname: Luo
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260, USA.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Carter
authors.affiliation: Department of Biochemistry and Biomedical Sciences and M. G. DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, ON L8S4L8, Canada.
authors.forename: Aida
authors.initials: A
authors.lastname: Razi
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260, USA.
authors.forename: Jumin
authors.initials: J
authors.lastname: Geng
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260, USA.
authors.forename: Shuai
authors.initials: S
authors.lastname: Shao
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260, USA.
authors.forename: Cuiyan
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of Biochemistry and Biomedical Sciences and M. G. DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, ON L8S4L8, Canada.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Ortega
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260, USA. Electronic address: jflovell@buffalo.edu.
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Lovell
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D002734:Chlorophyll / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D004339:Drug Compounding; D004355:Drug Stability; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007275:Injections, Intravenous; D008081:Liposomes; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010743:Phospholipids / Q000737:chemistry*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D010743:Phospholipids; D017319:Photosensitizing Agents; C506643:liposomal doxorubicin; D002734:Chlorophyll; C083998:2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: Cancer; Doxorubicin; Liposomes; Photodynamic therapy; Porphyrin; Vasculature