LIPOSOMAL INTEROCUL. DRUG DELIVERY IN VITRO AND IN VIVO
Project Number5R01EY003847-05
Contact PI/Project LeaderLERMAN, SIDNEY
Awardee OrganizationEMORY UNIVERSITY
Description
Abstract Text
Lectin-mediated binding of liposomes and delivery of specific agents by
this means to the ocular lens, cornea and other intraocular tissues will be
investigated. Whole eyes and human, rabbit and rat ocular tissues will be
used for in vitro studies and rabbits will be employed for in vivo
experiments. Liposomes will be prepared from various lipid (and
glycolipid) and fluorescein-labelled lectin combinations to assess the
effects of liposomal charge on binding of lectin to the vesicles and on the
binding of liposome-lectin complexes to ocular tissues. The effects of
vesicle size and form on binding, trapping efficiency, tissue distribution,
and intraocular pressure will also be evaluated. Binding will be assayed
in vitro and in vivo by fluorescence microscopy (FM), and scanning and
transmission electron microscopy. The fate of liposomes bound to ocular
tissues over specific time intervals will also be evaluated. The effects
of inclusion of cholesterol and dipalmitoylphosphatidyl-labelled compounds
will be assessed by fluorescence spectroscopy and liquid scintillation
counting of external aqueous phases of liposome suspensions at different
time intervals. Intracellular and intratissue delivery of fluorescent
markers by liposomes will be studied by FM, fluorescence spectroscopy and
UV-visible slit lamp densitography. Delivery of isotope labelled markers
will be analyzed by autoradiography and liquid scintillation counting of
tissue homogenates. Liposomal delivery of 8-methoxypsoralen will be
assessed by phosphorescence and EPR spectroscopy and other techniques.
Free radical scavengers and aldose reductase inhibitors will be delivered
to the ocular lens in vivo to evaluate their ability to protect the lens
from the development of radiation and sugar cataracts, respectively, and
any dose-response phenomena associated with them. Liposomally encapsulated
pilocarpine and nucleic acid analogues will be applied to the cornea in
vivo and the effects of liposomal delivery on diffusion of drugs across the
cornea and on drug activity on the cornea itself will be evaluated. Pilot
studies will also be carried out to assess the feasibility of using
liposomally encapsulated proteolytic enzymes to lyse cataracts in situ.
No Sub Projects information available for 5R01EY003847-05
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