Title : Chimeric and multicompartment drug delivery systems: Lessons learned and future perspectives
The aim of this investigation is to present the novel progress performed in recent years in the field of design and development of new nanocarriers used in pharmaceutical nanotechnology. Special attention is assigned to chimeric and multicompartment drug delivery systems. Chimeric drug delivery systems are those that consist of different materials i.e. lipids and polymers. Polymer-grafted liposomes and niosomes are presented in this study. The physicochemical characteristics of L-α-phosphatidylcholine, hydrogenated (Soy) (HSPC) and dipalmitoyl phosphatidyl choline (DPPC) liposomes, caused by the incorporation of a poly (oligoethylene glycol acrylate)-b-poly(lauryl acrylate) (POEGA-PLA) block copolymer at different molar ratios (chimeric liposomes) are investigated using Light Scattering and Imaging Techniques. Polymer-grafted liposomes composed of non-ionic surfactants i.e. Tween 80 and Span 80, cholesterol with and without poly(ethylene oxide)-b-poly(ε-caprolactone) (PEO-b-PCL) block copolymer are also studies with different and complementary techniques. These chimeric vesicles (liposomes and niosomes) exhibited stealth properties due to limited interactions between the plasma proteins and nanocarriers’ components. The results from the in vitro screening in cells showed low toxicity of the majority of the chimeric vesicles. The aforementioned chimeric systems found to be ideal for the loading and controlled release of model drug, especially those with water-insolubility problems.
Additionally, for this purpose, MWCNTs were oxidized via two different oxidation procedures and the oxidized MWCNTs were treated, in order to induce different surface charges onto MWCNTs-based materials. Then, we studied the cooperativity between the functionalized MWCNTs and DPPC and HSPC, by Differential Scanning Calorimetry. Strong interactions between the functionalized MWCNTs and the polar groups of phospholipids were observed in some cases, while in some other cases the nanotubes were oriented parallel to the membrane and located at the center of lipid bilayers. The presence of MWCNTs causes alterations of the size, size distribution and surface charge of the conventional HSPC and DPPC liposomes. The results from in vitro screening experiments showed low toxicity of the vast majority of the lipid/MWCNTs nanocarriers, even at high concentrations. The last observation indicates than the prepared systems are suitable and safe vectors for encapsulation of active pharmaceutical ingredients.
Furthermore, multicompartmentalized systems have been developed both for controlled delivery purpose and as models for cell biomimicry. Giant unilamellar polymersomes were prepared using an emulsion- centrifugation process, for which preformed liposomes were encapsulated into giant unilamellar poly-(butadiene)-b-poly(ethylene oxide) (PBut-b-PEO) vesicles (GUVs). Different types of liposomes were prepared using the thin-film hydration method followed by extrusion. Confocal microscopy and specific labeling using dyes was used to access the multicompartmentalized structure and morphology. As a proof of concept, we show an in vitro double-triggered release of dyes from the encapsulated liposomes using temperature variations.
Finally, from all the above examples, we can conclude that chimeric and multicompartment drug delivery vesicles are ideal technology platforms due to their biocompatibility and physicochemical properties.
Audience take away:
• The design and the development of advanced drug delivery systems composed of different biomaterials
• The advantages of these prepared systems
• The preparation protocol
• Their characteristics (physicochemical, morphological and thermodynamic)
• Their application in Nanomedicine