It has been shown recently that shearing of lyotropic lamellar
phases may lead to the formation of
relatively monodispersed multilayered vesicles named spherulites.
Freeze−fracture electron microscopy
analysis of such preparations, presented here, shows that their
three-dimensional organization is of a
space-filling polyhedral type, built up from very closely packed
spherulites, without any visible additional
water present neither in the center of the spherulites nor in between
them. Dilution of these preparations
leads to the separation of individual spherulites without appreciable
changes of their internal structure
(multilayered nature and spacing between the layers). Diluted
spherulites become spherical and are
separated by the water dispersions of much smaller vesicles,
originating probably from the fragmentation
of some external layers of concentrated spherulites.
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.
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