Arsonoliposomes: novel nanosized arsenic-containing vesicles for drug delivery.
Natural and synthetic arsenolipids, have been discovered, synthesized, and evaluated for their biological activity. Arsonolipids, are analogs of phosphonolipids, in which P has been replaced by As. The synthesis of arsonolipids has been explored and a simple one-pot method with high yield is currently available for their preparation. However, although arsonolipids posses interesting biophysical and biochemical properties their anticancer or antiparasitic activity is not considered adequate for therapeutic applications. But when arsonolipids are incorporated in liposomes, the vesicles formulated have interesting possibilities, as seen in a number of studies. In cell culture studies, nanosized arsonolipid-containing liposomes or else arsonoliposomes, showed increased toxicity against cancer cells (compared to that of arsenic trioxide) but at the same time were less toxic than arsenic trioxide for normal cells. Furthermore, arsonoliposomes also demonstrate antiparasitic activity in vitro. Nevertheless, As is rapidly cleared from blood after in vivo administration of arsonoliposomes, and this will highly limit possible therapeutic applications. In addition, the fact that arsonoliposomes were observed to aggregate and subsequently fuse into larger particles in presence of cations, may also be considered as a problem. Thereby, methods to modulate the stability of arsonoliposomes and, perhaps, their in vivo distribution (as surface property modification) are currently being investigated. In very recent experiments it has been shown that arsonoliposome pegylation results in the formation of liposomes with very high membrane integrity. In addition, pegylation results in increased physical stability of arsonoliposomes and abolishment of cation-induced aggregation and fusion. Nevertheless, further in vivo studies are required in order to prove if pegylation alters arsonoliposome in vivo kinetics in a positive way, without affecting their activity. From studies performed thus far it is concluded that arsonoliposomes are nanosized-vesicles with interesting properties that justify further exploitation towards the development of therapeutic systems for cancer or parasitic diseases.
Fatouros
Dimitris G
DG
Department of Pharmaceutics and Analytical Chemistry, The Danish University of Pharmaceutical Sciences, Universitetsparken 2, 2100, Copenhagen, Denmark.
Ioannou
Panayiotis V
PV
Antimisiaris
Sophia G
SG
D001151:Arsenic / Q000008:administration & dosage* / Q000737:chemistry*; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D003460:Crystallization / Q000379:methods*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D004563:Electrochemistry / Q000379:methods; D008081:Liposomes / Q000737:chemistry*; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D012399:Rotation
D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D008081:Liposomes; D001151:Arsenic