The advent of nanotechnology has revolutionized drug delivery in terms of improving drug efficacy and safety. Both polymer-based and lipid-based drug-loaded nanocarriers have demonstrated clinical benefit to date. However, to address the multifaceted drug delivery challenges ahead and further expand the spectrum of therapeutic applications, hybrid lipid-polymer nanocomposites have been designed to merge the beneficial features of both polymeric drug delivery systems and liposomes in a single nanocarrier. The present project aims to develop novel hybrid phospholipid vesicles characterized by an internal core with viscoelastic properties. In particular, it intends to define the optimal experimental conditions for gelation of the internal core of liposomes in order to maximize the stability of the resulting hybrid nanocostructs.
This aim will be pursued encapsulating polyethylene glycol-dimethacrylate (PEG-DMA) in the fluid aqueous compartment of liposomes with different composition, with the intent to modify their liquid inner compartment into a soft and elastic hydrogel. The effect of the molecular weight of PEG-DMA on the principal properties of the hybrid nanosystems will be investigated. Varying the molecular weight of PEG-DMA also its hydrophilic/lipophilic balance will be modified, for this reason a different localization of the polymer within the structure of liposomes and a different interaction with their membrane may be expected.
Therefore, the effect of the presence of the polymer and the length of its oxyethylene chain will be carefully studied in order to have insight on the stability and permeability of gel-core liposomes respect to conventional vesicles.
Hybrid liposomes with a core composed of a physically or chemically cross-linked network have been studied for their attractive features and special properties. Different approaches have been used for the development of hydrogel-liposome assemblies. In particular, they can be obtained by anchoring the lipid bilayer on the surface of preformed hydrogels, as in lipobeads [5-7], or by cross-linking encapsulated hydrophilic monomers inside the inner core of liposomal vesicles [8-10]. In both cases, a modified release kinetic of entrapped drugs could be obtained and, in addition, the presence of a stable polymeric scaffold provides an internal mechanical support to the lipid membrane mimicking the elastic protein network of the cytoskeleton. However, a great difference in the dimensions of the final assemblies exists. In fact, the second method allows preparing hybrid carriers of nanometric size and narrow size distribution, which can be used, in alternative to conventional liposomes, as nano-sized phospholipid-polymer hybrid assemblies (i.e. as such), or after removal of the external bilayer.
These lipid-polymer nanohybrids provide a flexible platform affording ample control over their physical, chemical and biological attributes. This degree of flexibility is of the uttermost importance to bypass the numerous extracellular and intracellular biological hurdles and to provide a suitable drug delivery solution for the ever-expanding collection of pharmaceuticals and adjuvants with greatly diverging physicochemical properties.
In addition, the potential of a more complex integrative drug delivery approach could come to light in the complex pathophysiology encountered in various diseases
A lot of research has been focused on the preparation, gelation procedure and structural characterization of these core gelled liposomes, but their ability in loading drugs, and their use as pharmaceutical carriers [11] remains largely unexplored. For this reason, starting from previous studies focused on the use of liposomes as template to create nanohydrogels [12], this project intends to create new hybrid systems investigating their ability to act as a carrier for drug delivery. Attention will be paid to the stability of the final hybrid vesicles under different conditions and under the effect of external stimuli.
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