Studying the colloidal behavior of chimeric liposomes by cryo-TEM, micro-differential scanning calorimetry and high-resolution ultrasound spectroscopy (original) (raw)
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Chimeric lipid/block copolymer nanovesicles: Physico-chemical and bio-compatibility evaluation
European Journal of Pharmaceutics and Biopharmaceutics, 2016
Chimeric systems are mixed nanovectors composed by different in nature materials and exhibit new functionalities and properties. The particular chimeric nanovectors, formed by the co-assembly of low and high molecular weight amphiphiles, have the potential to be utilized as drug delivery platforms. We have utilized two lipids, L-αphosphatidylcholine, hydrogenated (Soy)(HSPC) and 1,2-dipalmitoyl-sn-glycero-3phosphocholine(DPPC), and a poly(oligoethylene glycol acrylate)-b-poly(lauryl acrylate) (POEGA-PLA) block copolymer, at different molar ratios, in aqueous media. Light scattering, differential scanning calorimetry (DSC) and imaging techniques (cryo-TEM, AFM) were employed in order to elucidate the structure and properties of the nanostructures, as well as the cooperativity between the components. DSC experiments showed considerable interaction of the block copolymer with the lipid bilayers and suggested an inhomogeneous distribution of the copolymer chains and lateral phase separation of the components. Vesicle formation was observed in most cases by cryo-TEM with a chimeric membrane exhibiting kinks, in accordance to DSC data. A series of biocompatibility experiments indicated good in vitro biological stability and low cytotoxicity in vivo of the novel nanocarriers. Finaly, ibuprofen (IBU) was used as model drug in order to study the loading and the release properties of the prepared chimeric lipid/block copolymer vesicles.
2013
The complex nanoliposomes encapsulating both a hydrophilic drug vitamin C (vit C) and hydrophobic drug medium-chain fatty acids (MCFAs) was prepared by combining double emulsion method with dynamic high pressure microfluidization. The complex nanoliposomes was further freeze-dried under −86 °C for 48 h with sucrose at the sucrose/lipids ratio of 2:1(w/w) in order to enhance its stability. The freeze-dried complex nanoliposomes under the suitable conditions exhibited high entrapment efficiency of MCFAs (44.26 ± 3.34)%, relatively high entrapment efficiency of vit C (62.25 ± 3.43)%, low average size diameter (110.4 ± 7.28) nm and good storage stability at 4 °C for 60 days with slight changes in mean particle diameter and drug entrapment efficiencies. The results of transmission electron microscopy of freeze-dried complex nanoliposomes also showed that the freeze-dried samples with sucrose were stable without great increase in their particle sizes and without destroying their spherical shape. The results indicated that sucrose presented well protection effects in MCFAs-vit C complex nanoliposomes, suggesting the possibility of further usage in commercial liposomes.
Biophysical Journal, 2003
Poly(ethylene glycol) (PEG) decorated lipid bilayers are widely used in biomembrane and pharmaceutical research. The success of PEG-lipid stabilized liposomes in drug delivery is one of the key factors for the interest in these polymer/lipid systems. From a more fundamental point of view, it is essential to understand the effect of the surface grafted polymers on the physical-chemical properties of the lipid bilayer. Herein we have used cryo-transmission electron microscopy and dynamic light scattering to characterize the aggregate structure and phase behavior of mixtures of PEG-lipids and distearoylphosphatidylcholine or dipalmitoylphosphatidylcholine. The PEG-lipids contain PEG of molecular weight 2000 or 5000. We show that the transition from a dispersed lamellar phase (liposomes) to a micellar phase consisting of small spherical micelles occurs via the formation of small discoidal micelles. The onset of disk formation already takes place at low PEG-lipid concentrations (\5 mol %) and the size of the disks decreases as more PEG-lipid is added to the lipid mixture. We show that the results from cryo-transmission electron microscopy correlate well with those obtained from dynamic light scattering and that the disks are well described by an ideal disk model. Increasing the temperature, from 258C to above the gel-to-liquid crystalline phase transition temperature for the respective lipid mixtures, has a relatively small effect on the aggregate structure.
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2007
Complexation between linear poly-L-lysine (PLL) and negatively charged phosphocholine unilamellar liposomes has been investigated by means of dynamic light scattering, microelectrophoresis, and differential scanning calorimetry. It is found that complexation results in charge inversion (vesicle coating/stabilization) or vesicle aggregation depending on various experimental conditions. Complexation in dependence on PLL concentration and molecular mass, lipid phase state, rate and order of liposome and PLL mixing and time evolution of complexes are investigated and discussed. Aggregation profiles are determined and size distribution of the aggregates formed is studied, leading to the possibility of aggregation control. The time evolution of vesicle aggregation shows particle enlargement consisting in particle growth up to the irreversible formation of thermodynamically stable aggregates of about 2 μm in diameter. The formation of stable aggregates is in agreement with theoretical predictions of colloid particles aggregation by an interplay of long range electrostatic repulsion and short range attraction. Differential scanning calorimetry reveals that physical adsorption occurs exclusively on the vesicle surface and the lipidic organization is not significantly disturbed. The present study describes multivariable aspects of the complexation process between liposomes and polyions which results in the formation of a new class of still poorly defined colloids. These results allow establishing and optimization of a procedure for fabrication of polycation-stabilized vesicles to be used for various applications such as drug delivery.
Langmuir, 2003
The ability of a number of amphiphilic di-and triblock copolymers bearing short blocks of repeating lipid-mimetic units to sterically stabilize egg-phosphatidylcholine (EPC) liposomes has been studied by means of light scattering, cryogenic transmission electron microscopy (cryo-TEM), and fluorescence spectroscopy. The hydrophobic blocks contain 1-4 lipid-mimetic units, whereas the hydrophilic blocks consist of poly(ethylene glycol) (PEG) of average molecular weights close to 5000 Da. The effect of the chain architecture was investigated as well. The structural changes and membrane permeability were studied as a function of the amount of the incorporated copolymer. The structural investigations, performed by means of cryo-TEM, revealed that the maximum amount of the copolymer that can be incorporated in the EPC membrane without affecting the liposome integrity increases with increasing number of the lipidmimetic anchors per single copolymer chain. This helps the formation of a dense and thick PEG protective layer which, in turn, is expected to enhance the liposome longevity. At the same time, the membrane permeability, investigated using a hydrophilic dye as a probe, was only slightly affected by the incorporation of the copolymers. The structural changes and membrane permeability are discussed in light of the shape of the macromolecules and the phase propensity of the steric stabilizers.
Lipid and Polymeric Nanocapsules
Drug Carriers [Working Title]
In recent years, innovative drug nanocarriers have been developed to enhance stability, bioavailability, and provide sustained release. In this chapter, systems based on natural macromolecules, lipids, or polymeric/polyelectrolyte nanocapsules and their principal chemical and functional characteristics are described. Nano-vesicular systems are especially relevant in different fields. Particularly, a promising potential is offered by systems based on colloidal nanocapsules, that exhibit a typical core-shell structure in which the drug can be confined into the cavity or in the polymeric coating that surrounds it. Both the cavity and the active substance can be lipophilic or hydrophilic and in solid or liquid form depending on the materials and methods used, making these nanocapsules attractive carriers for drug delivery. In addition, a compilation of different methods and materials employed in the preparation of these nanosystems and a recent review of applications of lipid and polyme...
Colloids and Surfaces B-biointerfaces, 2011
In this work, didecyldimethylammonium bromide (DDAB) and 1,2-dioleoyl-sn-glycero-3phosphatidylethanolamine (DOPE) (2.5:1) were used to prepare liposomes coated with polyacrylic acid (PAA) using "in situ" polymerization with 2.5, 5 and 25 mM of acrylic acid (AA). The PAA concentrations were chosen to achieve partially to fully covered capsules, and the polymerization reaction was observed with real-time monitoring using dynamic light scattering (NanoDLS). The DDAB:DOPE liposomes showed stability in the tested temperature range (25-70 • C), whereas the results confirmed the success of the polymerization according to superficial charge (zeta potential of +66.7 ± 1.2 mV) results and AFM images. For the liposomes that were fully coated with PAA (zeta potential of +0.3 ± 3.9 mV), cytotoxicity was independent of the concentration of albumin. Cationic liposomes and nanocapsules of the stable liposomes coated with PAA were obtained by controlling the surface charge, which was the most important factor related to cytotoxicity. Thus, a potential, safe drug nanocarrier was successfully developed in this work.
Structure and organization of phospholipid/polysaccharide nanoparticles
Journal of Physics-condensed Matter, 2008
In recent years nanoparticles and microparticles composed of polymeric or lipid material have been proposed as drug carriers for improving the efficacy of encapsulated drugs. For the production of these systems different materials have been proposed, among them phospholipids and polysaccharides due to their biocompatibility, biodegradability, low cost and safety. We report here a morphological and structural investigation, performed using cryo-TEM, static light scattering and small angle neutron and x-ray scattering, on phospholipid/saccharide nanoparticles loaded with a lipophilic positively charged drug (tamoxifen citrate) used in breast cancer therapy. The lipid component was soybean lecithin; the saccharide one was chitosan that usually acts as an outer coating increasing vesicle stability. The microscopy and scattering data indicate the presence of two distinct nanoparticle families: uni-lamellar vesicles with average radius 90 Å and multi-lamellar vesicles with average radius 440 Å. In both families the inner core is occupied by the solvent. The presence of tamoxifen gives rise to a multi-lamellar structure of the lipid outer shell. It also induces a positive surface charge into the vesicles, repelling the positively charged chitosan molecules which therefore do not take part in nanoparticle formation.
Loading and Protection of Hydrophilic Molecules into Liposome-Templated Polyelectrolyte Nanocapsules
Langmuir, 2014
Compartmentalized systems produced via the layer-bylayer (LbL) self-assembly method have been produced by alternatively depositing alginate and chitosan layers onto cores of liposomes. The combination of dynamic light scattering (DLS), ζ potential, and transmission electron microscopy (TEM) techniques provides detailed information on the stability, dimensions, charge, and wall thickness of these polyelectrolyte globules. TEM microphotographs demonstrate the presence of nanocapsules with an average diameter of below 300 nm and with a polyelectrolyte wall thickness of about 20 nm. The possibility of encapsulating and releasing molecules from this type of nanocapsule was demonstrated by loading FITC-dextrans of different molecular weights in the liposome system. The release of the loaded molecules from the nanocapsule was demonstrated after liposome core dissolution. Even at low molecular weight (20 kDa), the nanocapsules appear to be appropriate for prolonged molecule compartmentalization and protection. By means of the Ritger−Peppas model, non-Fickian transport behavior was detected for the diffusion of dextran through the polyelectrolyte wall. Values of the diffusion coefficient were calculated and yield useful information regarding chitosan/alginate hollow nanocapsules as drug-delivery systems. The influence of the pH on the release properties was also considered. The results indicate that vesicletemplated hollow polyelectrolyte nanocapsules show great potential as novel controllable drug-delivery devices for biomedical and biotechnological applications.