title: Long-Circulating, pH-Sensitive Liposomes.
abstract: A major limiting factor for the wide application of pH-sensitive liposomes is their recognition and sequestration by the phagocytes of the reticuloendothelial system, which conditions a very short circulation half-life. Typically prolonged circulation of liposomes is achieved by grafting their membranes with pegylated phospholipids (PEG-lipids), which have been shown, however, to deteriorate membrane integrity on one hand and to hamper the pH-responsiveness on the other. Hence, the need for novel alternative surface modifying agents to ensure effective half-life prolongation of pH-sensitive liposomes is a subject of intensive research. A series of copolymers having short blocks of lipid-mimetic units has been shown to sterically stabilize conventional liposomes based on different phospholipids. This has prompted us to broaden their utilization to pH-sensitive liposomes, too. The present contribution gives a thorough account on the chemical synthesis of these copolymers their incorporation in DOPE:CHEMs pH-sensitive liposomes and detailed explanation on the battery of techniques for the biopharmaceutical characterization of the prepared formulations in terms of pH-responsiveness, cellular internalization, in vivo pharmacokinetics and biodistribution.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav Str., 1000, Sofia, Bulgaria. dmomekova@yahoo.com.
authors.forename: Denitsa
authors.initials: D
authors.lastname: Momekova
authors.affiliation: Institute of polymers, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Rangelov
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav Str., 1000, Sofia, Bulgaria.
authors.forename: Nikolay
authors.initials: N
authors.lastname: Lambov
mesh_terms: D000818:Animals; D002450:Cell Communication; D045744:Cell Line, Tumor; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D008856:Microscopy, Fluorescence; D010714:Phosphatidylethanolamines / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D010743:Phospholipids / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry; D051381:Rats; D014018:Tissue Distribution
chemical_list: D008081:Liposomes; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D011108:Polymers; C094877:dioleoyl phosphatidylethanolamine
keywords: Block copolymers; PEG-lipids; Steric stabilization; pH-sensitive liposomes