The spherulites(TM): a promising carrier for oligonucleotide delivery.
Concentric multilamellar microvesicles, named spherulites(TM), were evaluated as an oligonucleotide carrier. Up to 80% oligonucleotide was encapsulated in these vesicles. The study was carried out on two different spherulite(TM) formulations. The spherulite(TM) size and stability characteristics are presented. Delivery of encapsulated oligonucleotide was performed on a rat hepatocarcinoma and on a lymphoblastoid T cell line, both expressing the luciferase gene. We showed that spherulites(TM) were able to transfect both adherent and suspension cell lines and deliver the oligonucleotide to the nucleus. Moreover, 48-62% luciferase inhibition was obtained in the rat hepatocarcinoma cell line when the antisense oligonucleotide targeted to the luciferase coding region was encapsulated at 500 nM concentration in spherulites(TM) of different compositions.
Laboratoire de Biophysique, Muséum National d'Histoire Naturelle, INSERM U201, CNRS UMR 8646, 43 rue Cuvier, 75231 PARIS Cedex 05, France.
N
N
Mignet
A
A
Brun
C
C
Degert
B
B
Delord
D
D
Roux
C
C
Hélène
R
R
Laversanne
J C
JC
François
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004337:Drug Carriers; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D008114:Liver Neoplasms, Experimental; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics; D009838:Oligodeoxyribonucleotides; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage* / Q000494:pharmacology; D009843:Oligoribonucleotides; D051381:Rats; D011994:Recombinant Proteins / Q000032:analysis; D013601:T-Lymphocytes; D014162:Transfection / Q000379:methods*; D014407:Tumor Cells, Cultured
D004337:Drug Carriers; D008164:Luminescent Proteins; D009838:Oligodeoxyribonucleotides; D020319:Oligodeoxyribonucleotides, Antisense; D009843:Oligoribonucleotides; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins