Intravitreal administration of antisense oligonucleotides: potential of liposomal delivery.
Antisense oligonucleotides are short synthetic fragments of genes that are able to inhibit gene expression after being internalized by cells. They can therefore be used as antiviral compounds particularly, for the treatment of ocular viral infections (i.e. Herpes simplex virus or Cytomegalovirus, CMV). Antisense oligonucleotides are however poorly stable in biological fluids and their intracellular penetration is limited. Although oligonucleotides are now currently used in therapeutics for the treatment of CMV by intravitreal injection (Vitravene) their main drawbacks impose to repeat the number of administrations which can be very harmful and damaging. A system that is able to permit a protection of oligonucleotides against degradation and their slow delivery into the vitreous would be more favorable for improving patient compliance. The use of liposomes for intravitreal administration can be very promising since these lipid vesicles are able to protect oligonucleotides against degradation by nucleases and they allow to increase the retention time of many drugs in the vitreous. In this review, the potentialities of liposomes for the intravitreal delivery of oligonucleotides will be discussed.
Bochot
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A
Université Paris XI, Centre d'études Pharmaceutiques, UMR CNRS 8612, Châtenay-Malabry, France.
Couvreur
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P
Fattal
E
E
D000287:Administration, Topical; D000818:Animals; D002986:Clinical Trials as Topic; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D015828:Eye Infections, Viral / Q000188:drug therapy*; D006801:Humans; D008081:Liposomes / Q000493:pharmacokinetics*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000633:toxicity; D010316:Particle Size; D010349:Patient Compliance; D014822:Vitreous Body
D003692:Delayed-Action Preparations; D008081:Liposomes; D016376:Oligonucleotides, Antisense