Long-circulating, pH-sensitive liposomes.
A major limiting factor for the wide application of pH-sensitive liposomes is their recognition and sequestration by the phagocytes of the reticulo-endothelial 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 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.
Momekova
Denitsa
D
Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Medical University-Sofia, Sofia, Bulgaria.
Rangelov
Stanislav
S
Lambov
Nikolay
N
D000818:Animals; D045744:Cell Line, Tumor; D002788:Cholesterol Esters / Q000737:chemistry*; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry* / Q000493:pharmacokinetics*; D008297:Male; D015394:Molecular Structure; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D002788:Cholesterol Esters; D008081:Liposomes; D010714:Phosphatidylethanolamines; C013440:cholesteryl succinate