TY - JOUR
AU - Philippot, Jean R.
AB - AbstractJ. R. Philippot and B. Lebleu acknowledge the Agence Nationale de Recherche sur le SIDA and the Association de Recherche contre le Cancer for support. The authors thank A. Bienveniie from URA-CNRS 1856 (University Montpellier II) for many fruitful discussions during the course of this study. We thank M.-T. Cabanis from the Laboratory of Analytical Chemistry (Faculty of Pharmacy, Montpellier) for titrating calcium. J. P. Bongartz was the recipient of a postdoctoral fellowship from ANRS.The degradation of a drug, its toxicity, the unsuitable target binding or intracellular routing may be circumvented by an efficient drug delivery system. The efficacy of pH-sensitive liposomes is well documented for these purposes: These liposomes have a lipidic composition that makes escape from the endosome and delivery into the cytoplasm possible. The efficacy of pH-sensitive liposomes, comprising dioleoyl phosphatidyl ethanolamine, oleic acid, and cholesterol (DOPE/OA/Chol), loaded with polyrI:polyrC (polyIC), has been reported to induce interferon. This report evaluated the ability of such liposomes to deliver antisense phosphodiester oligonucleotides (ODNs). These anti-sense ODNs were intended to inhibit the vesicular stomatitis virus (VSV) whose development is restricted to the cytoplasm. The results show that free antisense ODNs failed to induce an antiviral effect up to 40 μM. On the contrary, encapsulated ODNs in pH-sensitive liposomes had an effect on L929 cells at a concentration around 5 μM ODN, in serum free and calcium free medium. This effect was obtained with pH-sensitive liposomes, comprising DOPE/cholesterol hemisuccinate (CHEMS)/Chol, which are less toxic than DOPE/OA/Chol liposomes. In these experimental conditions, liposomes were stable and pH-sensitive for several hours. Their potential was limited by the lipid toxicity when higher concentrations were required.
TI - pH-Sensitive Liposomes and Antisense Oligonucleotide Delivery
JF - Drug Delivery
DO - 10.3109/10717549609031175
DA - 1996-01-01
UR - https://www.deepdyve.com/lp/taylor-francis/ph-sensitive-liposomes-and-antisense-oligonucleotide-delivery-qvtVM2TBOC
SP - 67
EP - 73
VL - 3
IS - 2
DP - DeepDyve
ER -