Lipogels for Encapsulation of Hydrophilic Proteins and Hydrophobic Small Molecules (original) (raw)
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Faraday Discussions, 2005
Delivery of therapeutics (drugs, radionuclides or genes) in vivo can be optimized when carried by a targeting delivery vehicle such as a surfactant vesicle, polymeric micelle or other polymer-coated colloidal particulate. In the present communication, we propose a general method based on self-assembly principles, to construct lipid-polymer bilayer vesicles whose featured characteristics may be altered according to the polymer molecule used, thus be easily designed along the needs of a particular delivery application. Polymer molecules containing non-polymerizable (polypropylene) and polymerisable (methacrylate) hydrophobic groups were used to construct lipid-polymer vesicles by following two different methods of preparation. In accord with our previous findings, when both types of polymer molecules are added to pre-formed liposomes, only weak adsorption onto the lipid surface occurs. Preparation of the vesicles by pre-mixing the lipid and polymer molecules has proved essential in order to allow the hydrophobic blocks of the copolymers to participate as integral parts of the bilayer. Anchoring of a polymerisable polymer onto the lipid bilayer by hydrophobic interactions, resulted in steric stabilization of the vesicles. When UV polymerization of the bilayer-incorporated [Methyl(PEG) 2000 MA] polymer was induced, inter-vesicle fusion was triggered. Direct cryo-EM imaging of fusion between the PEG-coated liposomes has been observed. Such sterically stabilised fusogenic vesicles were constructed as potential triggered-release delivery systems, responsive to a variety of external stimuli depending on the type of polymerisable, hydrophobic group in the polymer molecule. By altering the properties of the incorporated hydrophobic group, liposomes able to fuse in response to initiators milder than UV light, such as green or red light, sound, temperature, oxygen or pH can be engineered.
UV-Induced Gelation on Nanometer Scale Using Liposome Reactor
Macromolecules, 2002
A protocol for preparation of polymer hydrogel spherical particles on a nanometer scale (nanogels) was developed. The protocol includes encapsulation of hydrogel-forming components into liposomes, UV-induced polymerization within the liposomes, solubilization of the lipid bilayer by detergent, removal of the phospholipid, detergent molecules, and their micelles by dialysis, and drying nanogels by evaporation in a temperature gradient. Dynamic light scattering technique was employed to characterize the size distribution of poly(acrylamide), poly(N-isopropylacrylamide), and poly(N-isopropylacrylamideco-1-vinylimidazole) hydrogel particles. Hydrophobic chains of N-octadecylacrylamide were immobilized onto the surface of the poly(N-isopropylacrylamide-co-1-vinylimidazole) hydrogel particles to use them as anchors for attaching the nanogels onto the lipid bilayers. The diameter of the nanogels prepared varied between 30 and 300 nm. The solvent, temperature, and pH sensitivities of the liposomes, nanogels, and their mixtures were studied. It was found that the phospholipid bilayer always coats the surface of both unanchored and anchored hydrogel particles upon mixing. Aggregation of the lipid bilayer-coated nanogels (lipobeads) was observed when the gel particles collapsed. The mechanism of aggregation differs for the lipobeads containing unanchored cores and those containing anchored hydrogel cores. The hydrogel-liposome structures of a nanometer size are of potential importance for applications such as biomimetic sensory systems, controlled release devices, and multivalent receptors. Figure 11. z-Average diameter of the anchored PNIPA-VI lipobeads (a) as a function of temperature upon heating/cooling and (b) as a function of pH.
A Microreactor with Thousands of Subcompartments: Enzyme-Loaded Liposomes within Polymer Capsules
Angewandte Chemie International Edition, 2009
Nanoengineered carriers that fulfill simple predefined cell activities have potential as a powerful therapeutic tool to replenish lost or missing cellular functions. The first key challenge in the creation of such systems lies in the design of a multifunctional carrier that accommodates controlled encapsulation and release of drugs and reagents ranging from small molecules to proteins and nucleic acids, and which simultaneously allows interaction with the surrounding environment. Two notable platforms that are currently considered as potential synthetic vessels, namely liposomes and multilayered polymer capsules, [4, fulfill in part some of these requirements, however, both carrier systems have some inherent limitations. Polymer capsules possess the desired structural integrity and are well-suited for the encapsulation of macromolecular cargo. Furthermore, their semipermeable nature is an important feature that allows them to communicate with the external milieu. However, in their native form, their permeability makes them unsuitable in providing a protective barrier for small drugs and reagents, as they can freely diffuse across the capsule walls. [4] On the other hand, small unilamellar liposomes provide effective encapsulation for small and medium-sized cargo, but can be susceptible to structural instability and are largely impermeable to their surroundings. We report herein a method to create capsosomes, which are polymer capsules that contain liposomal subcompartments, to maximize the benefits offered by both polymer multilayer capsules and liposomes, and to deliver a new carrier platform ). We show that the capsosomes inherit the structural stability of the polymer capsules, and have a semipermeable nature; the liposomes are capable of restricting the access of solutes to an encapsulated model enzyme, b-lactamase. To achieve these properties, we have pioneered the use of cholesterol-modified polymers to maximize and control the loading of liposomes into polymer multilayer films, and have developed a benign technique to obtain disulfide-stabilized polymer capsules without the use of detrimental oxidizing reagents. We have independently verified the loading of the enzyme into the liposomes as well as the liposome loading in the polymer capsules. We have also performed a quantitative enzymatic assay to substantiate the encapsulation and functionality of the enzyme within the liposomal subcompartments and to estimate the number of subcompartments within the capsosomes. Each of these steps has fundamental merits, and, when taken together, this work represents significant progress toward the assembly of functional vehicles that can serve as artificial organelles.
Frontiers in Bioengineering and Biotechnology
Lipid based nanoparticulate formulations have been widely used for the encapsulation and sustain release of hydrophilic drugs, but they still face challenges such as high initial burst release. Nanolipogel (NLG) emerges as a potential system to encapsulate and deliver hydrophilic drug while suppressing its initial burst release. However, there is a lack of characterization of the drug release mechanism from NLGs. In this work, we present a study on the release mechanism of hydrophilic Dextran-Fluorescein Isothiocyanate (DFITC) from Poly (ethylene glycol) Diacrylate (PEGDA) NLGs by using different molecular weights of PEGDA to vary the mesh size of the nanogel core, drawing inspiration from the macromolecular crowding effect in cells, which can be viewed as a mesh network of undefined sizes. The effect is then further characterized and validated by studying the diffusion of DFITC within the nanogel core using Fluorescence Recovery after Photobleaching (FRAP), on our newly developed c...
Biomolecular Science of Liposome-Nanoparticle Constructs
Molecular Crystals and Liquid Crystals, 2009
Phospholipid-nanoparticle constructs, formed by allowing nanoparticles to adsorb to the outer leaflet of liposomes, are found to be stabilized against fusion with one another. Here, through single-particle tracking by epifluorescence microscopy, we explore their use as novel colloidal particles -flexible and hollow colloidal particles that contrast strikingly with colloids of the conventional type. At the singleliposome level, the distribution of diffusion coefficients is quantified. Biomolecular function is addressed through experiments in which we explore the access of receptor to liposome-immobilized ligand, finding that receptor binding persists over a range of nanoparticle surface coverage where liposome fusion and large-scale aggregation is prevented. This opens the door to designing newer and more flexible types of tailor-made materials with desirable functionality.
Liposome-Nanogel Structures for Future Pharmaceutical Applications
Current Pharmaceutical Design, 2006
Nanoparticles have been extensively studied as drug delivery systems. In this review, we focus on a relatively new type of nanoparticles -lipobeads -a liposome-hydrogel assembly as a novel drug delivery system. An appropriate assemblage of spherical hydrogel particles and liposomes combines the properties of both classes of materials and may find a variety of biomedical applications. The bi-compartmental structure of lipobeads is a natural configuration. Thus, the technology of their preparation can be a key step of designing more stable and effective vaccines. Biocompatibility and stability, ability to deliver a broad range of bioactive molecules, environmental responsiveness of both inner nanogel core and external lipid bilayer, and individual specificity of both compartments make the liposome-nanogel design a versatile drug delivery system relevant for all known drug administration routes and suitable for different diseases with possibility of efficient targeting to different organs. New findings on reversible and irreversible aggregation of lipobeads can lead to novel combined drug delivery systems regarding lipobeads as multipurpose containers. The research on hydrogelliposome submicrometer structures has just begun and fundamental studies on interactions between hydrogels and liposomes are in demand.
Lipid–Polymer Hybrid Nanoparticles: Synthesis, Characterization and Applications
Nano LIFE, 2010
Nanotechnology has been extensively explored in the past decade to develop a myriad of functional nanostructures to facilitate the delivery of therapeutic and imaging agents for various medical applications. Liposomes and polymeric nanoparticles represent two primary delivery vehicles that are currently under investigation. While many advantages of these two particle platforms have been disclosed, some intrinsic limitations remain to limit their applications at certain extent. Recently, a new type of nanoparticle platform, named lipid–polymer hybrid nanoparticle, has been developed that combines the positive attributes of both liposomes and polymeric nanoparticles while excluding some of their shortages. This new nanoparticle consists of a hydrophobic polymeric core, a lipid shell surrounding the polymeric core, and a hydrophilic polymer stealth layer outside the lipid shell. In this review, we first introduce the synthesis and surface functionalization techniques of the lipid–polym...
International Journal of Nanomedicine, 2019
Lipid-polymer hybrid nanoparticles (LPHNPs) are next-generation core-shell nanostructures, conceptually derived from both liposome and polymeric nanoparticles (NPs), where a polymer core remains enveloped by a lipid layer. Although they have garnered significant interest, they remain not yet widely exploited or ubiquitous. Recently, a fundamental transformation has occurred in the preparation of LPHNPs, characterized by a transition from a two-step to a one-step strategy, involving synchronous self-assembly of polymers and lipids. Owing to its two-in-one structure, this approach is of particular interest as a combinatorial drug delivery platform in oncology. In particular, the outer surface can be decorated in multifarious ways for active targeting of anticancer therapy, delivery of DNA or RNA materials, and use as a diagnostic imaging agent. This review will provide an update on recent key advancements in design, synthesis, and bioactivity evaluation as well as discussion of future clinical possibilities of LPHNPs.
Angewandte Chemie International Edition, 2012
A major challenge for biophysical studies of membrane proteins is obtaining stable, homogenous samples. Traditional detergent solubilization and liposome-based methods of reconstitution may lead to protein inactivation, heterogeneous and polydisperse sized particles, and sample aggregation. While membrane scaffold protein (MSP) stabilized nanodiscs have facilitated the formation of monodisperse protein samples, [2] a drawback is the detergent-based preparation method. Here we present a physicochemical characterization of polymer-stabilized lipid particles termed Lipodisq, a novel nanosized lipid-based platform capable of incorporating membrane proteins. [3] The polymers used in the Lipodisq technology can solubilize commonly used lipids such as dimyristoylphosphatidylcholine (DMPC) without the use of detergents. The small size of Lipodisq (diameter of around 9-10 nm at pH 7.4) renders them potentially suitable for many biophysical methodologies, including electron paramagnetic resonance (EPR) and nuclear magnetic resonance (NMR) spectroscopies, electron microscopy (EM), and circular dichroism (CD) spectroscopy.