(719d) Lipid-Based Drug Delivery Systems – Understanding Molecular Packing, Interaction, and Degradation Kinetics and Thermodynamics

Zhang, P. - Presenter, University of Illinois at Chicago
Liu, Y., University of Illinois at Chicago
Lin, B., NSF's ChemMatCARS, University of Chicago
Bu, W., NSF's ChemMatCARS, University of Chicago

Liu, Ying Liu, Ying 2 2 2019-04-13T04:56:00Z 2019-04-13T04:57:00Z 2019-04-13T04:57:00Z 1 382 2182 18 5 2559 16.00

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" times new roman>Lipid-based Drug Delivery Systems – Understanding
Molecular Packing, Interaction, and Degradation Kinetics and Thermodynamics

Specific targeting to the diseased
cell/tissue without affecting the healthy ones is the Holy Grail for the
treatment of complex diseases. In the past two decades, several types of
nanomedicines have shown promising results to achieve this dream. Among current
systems of nanomedicines, liposomes have gained extensive attention as carriers
for a wide range of drugs due to being both nontoxic and biodegradable since
they are composed of substances naturally occurring in biological membranes.
For this reason, liposomal-vesicle-based nanomedicines are the only FDA
approved ones currently. Liposomal structures and physicochemical characteristics
could be altered by a wide range of choices of phospholipids, polymer
conjugation, and addition of membrane proteins. This flexibility permits the
modification of liposome behavior in vivo
and their design according to specific therapeutic needs. However, the number
of possibilities is enormous and optimization of the structure is not feasible
by empirical trials. Systematic understanding of molecular interactions of
polymer-phospholipids with enzymes is necessary, but challenging.

One step toward the goal of
developing “smart” liposomal nanoparticles for targeting delivery of
biologically active payloads, we have systematically studied the molecular
packing and molecular interactions between enzymes and polymer-phospholipids. Liposome
degradation kinetics was measured using dynamic light scattering. Evolution of
giant unilamellar vesicles (GUVs) consisting of
saturated and unsaturated phospholipids upon adding sPLA2 was
monitored under fluorescent microscopy. X-ray reflectivity, which provides information
on molecular organization across the interface, and grazing-incidence X-ray
diffraction (GIXD), which reveals the two-dimensional crystal structures at the
interface, were applied to characterize the interfacial structures of the
monolayers before and after enzyme-catalyzed degradation. Through these
experimental measurements, the effects of PEGylation and polyunsaturated lipids
on lipid degradation were revealed. The highly ordered bilayer and multilayer
structures of fatty acid-Ca2+ complex yield from saturated lipid
hydrolysis was also identified. The results of this study advance our
understanding on the role of enzymes in related physiological processes and
lead to a mechanism-based approach to designing and optimizing lipid-based