Types Of Liposomes Research Articles

The influence of lipid composition and surface charge on biodistribution of intact liposomes releasing from hydrogel-embedded vesicles

Mixed drug delivery systems possess advantages over discrete systems, and can be used as a strategy to design more effective formulations. They are more valuable if the embedded particles perform well, rather than using drugs that have been affected by the surrounding vehicle. In order to address this concept, different liposomes have been incorporated into hydrogel to evaluate the potential effect on the controlled release of liposomes. Radiolabeled liposomes, with respect to different acyl chain lengths (DMPC, DPPC, or DSPC) and charges (neutral, negative [DSPG], or positive [DOTAP]) were integrated into chitosan-glycerophosphate. The results obtained from the biodistribution showed that the DSPC liposomes had the highest area under the curve (AUC) values, both in the blood (206.5%ID/gh(-1)) and peritoneum (622.3%ID/gh(-1)), when compared to the DPPC and DMPC formulations, whether in liposomal hydrogel or dispersion. Interesting results were observed in that the hydrogel could reverse the peritoneal retention of negatively charged liposomes, increasing to 8 times its AUC value, to attain the highest amount among all formulations. The interactions between the liposomes and chitosan-glycerophosphate, confirmed by the Fourier transform infrared (FTIR) spectra as shifted characteristic peaks, were observed in the combined systems. Overall, the hydrogel could control the release of intact liposomes, which could be manipulated by both the liposome type and interactions between the two vehicles.

Ocular Tissue Distribution of Topically Applied PEGylated and Non-PEGylated Liposomes

Topical ocular drug delivery has always been a challenging area due to poor ocular bioavailability. Improved drug delivery systems such as liposomes are capable of entrapping both the lipophilic and hydrophilic substances. Therefore, they are effective formulations for drug delivery to targeted structure. PEGylated-liposomes are known to have stealth properties due to their ability of resisting removal by phagocytic cells. This study compares ability of PEGylated-and nonPEGylated-liposomes in delivering lipophilic fluorescent dye, Dil, to several ocular tissues. Sprague-Dawley rats (190-250g) were divided into 2 groups that received unilateral topical application of single drop of PEGylated-liposome (PEG-Lip) or nonPEGylated-liposome (Lip). Contralateral eyes served as control and received no treatment. Animals were sacrificed at several time points, post-instillation, and eyeballs were enucleated. Cryostat sectioning was done and sections were viewed with fluorescence microscope. Fluorescence intensity (FI) was calculated and quantified. In treated eyes, nonPEGylated-liposomes showed faster corneal permeation compared to PEGylated-liposomes. NonPEGylated-liposomes also showed faster availability in ciliary body and retina of treated eyes, possibly a consequence of faster corneal permeation. Their higher engulfment by macrophages and subsequent localization in vascular tissue may also be a contributing factor. In contralateral eyes, both groups showed dye distribution indicating their significant systemic distribution. Higher availability of non-PEGylated-liposomes in contralateral eyes also indicated that they are more likely to undergo phagocytosis and consequently faster removal. In conclusion, PEG-lip showed slower corneal permeation in the treated eyes. Both types of liposomes undergo significant systemic absorption. Since, PEG-lip are more resistant to phagocytosis, they may provide more sustained drug delivery.

Highly-Branched Poly(N-isopropylacrylamide) as a Component in Poly(dopamine) Films

Mixed one-step poly(dopamine) (PDA)/highly branched poly(N-isopropylacrylamide) (pNiPAAm) coatings have been assembled and characterized by X-ray photoelectron spectroscopy (XPS), UV-vis spectroscopy, atomic force microscopy, and quartz crystal microbalance with dissipation monitoring (QCM-D) depending on the deposition temperature below and above the lower critical solution temperature (LCST) of the pNiPAAm. Mixed films were confirmed. The protein adsorption at 24 °C was found to be reduced with increasing amount of pNiPAAm in the mixed coatings, while there was no difference observed for proteins deposition at 39 °C. Further, the ability of these mixed coatings in comparison to the pure PDA and pNiPAAm films to serve as capping layer for surface-immobilized zwitterionic or positively charged liposomes has been assessed by QCM-D. The adhesion of hepatocytes, macrophages, and myoblast to these liposomes-containing hybrid coatings and the uptake of fluorescent lipids from the surface by the adhering cells depending on the capping layers were compared. The latter aspect was found to be dependent on the used capping layer and the type of liposome as carrier for the fluorescent lipid, with the highest uptake found for positive liposomes and pure pNiPAAm as capping layer. Taken together, the assembled hybrid coatings have the potential to be used as functional coatings toward surface-mediated drug delivery.

Fliposomes: new amphiphiles based on trans-3,4-bis(acyloxy)-piperidine able to perform a pH-triggered conformational flip and cause an instant cargo release from liposomes

Amphiphilic trans-3,4-bis(acyloxy)-1-benzylpiperidines able to perform a pH-triggered conformational flip (flipids) have been suggested as components of a new type of pH-sensitive liposomes (fliposomes). According to 1H NMR, their acid-induced conformational flip occurs in methanol-d4 when the apparent pD decreases from 6 to 3. The protonation-generated intramolecular hydrogen bond and electrostatic interactions make the conformer with axial acyloxy-groups predominant, which drastically increases the separation of hydrocarbon chains. The power of this trigger was estimated as ⩾10 kJ/mol. This flip perturbs the liposome membrane causing rapid release of the liposome cargo specifically in response to lowered pH. The pH-sensitive fliposomes containing one of these flipids, POPC and PEG-ceramide, and loaded with ANTS/DPX performed a content release within a few seconds at pH <5 demonstrating a potential of the piperidine derivatives as pH-switches for the design of liposomes for drug/gene delivery.

Self‐calibrated concentration measurements of polydisperse nanoparticles

Quantitative characterization of nanoparticles, e.g. accurate estimation of concentration distributions, is critical to many pharmaceutical and biological applications. We present a method that enables for the first time highly accurate size and absolute concentration measurements of polydisperse nanoparticles in solution, based on fluorescence single particle tracking, that are self-calibrated in the sense that the detection region volume is estimated based on the tracking data. The method is evaluated using simulations and experimental data of polystyrene nanospheres in water/sucrose solution. In addition, the method is used to quantify aggregation and clearance of different types of liposomes after intravenous injection in rats, where additional and more accurate information can be obtained that was previously unavailable, which can help elucidate their usefulness as drug carriers.

Effect of iron liposomes on anemia of inflammation

Supplementation with iron-fortified foods is an effective method for treating iron deficiency diseases. However, traditional iron agents used to treat anemia of inflammation (AI) have little effect. In this study, two types of iron liposomes, heme liposomes (HEME-LIP) and ferric citrate liposomes (FAC-LIP), were prepared by the rotary-evaporated film-ultrasonication method, and the encapsulation efficiencies, microstructures, size distributions and zeta potentials were assessed. Both types of iron liposomes showed stable physical characteristics. When used to treat rat models of AI, FAC-LIP and HEME-LIP could increase serum iron levels by 119% and 54% higher than did ferric citrate (FAC) and heme, respectively. Furthermore, the hepcidin, a key regulator of iron homeostasis was up-regulated by these iron liposomes, especially by HEME-LIP. These results indicate that the absorption of iron liposomes was improved over that of unencapsulated iron agents. Thus, iron liposomes may be used to fortify food in treating iron deficiency diseases, especially AI.

Size distribution and dye release properties of submicron liposome aerosols

Abstract Liposome aerosols have been used in controlled release drug delivery applications like insulin, doxorubicin and ciprofloxacin. Limiting the size distribution to submicron particle sizes could enhance pulmonary targeting. This study assessed the use of simple air-jet nebulisation to produce submicron liposome aerosol powders through control of precursor suspension colloidal properties. Colloidal properties of the suspension and particle type, vis-a-vis payload size and controlled release, were varied by changing liposome type (unilamellar and oligolamellar) and lipid concentration. The effects on powder size-distribution and dye-release properties were studied. The influences of (i) nebulisation forces and (ii) subsequent droplet drying were investigated, on changes induced in controlled release properties of the aerosol powders. Liposome aerosols had similar size-distribution properties (median mobility diameter 0.07–0.16 μm and aerodynamic diameter 0.3–1.0 μm), regardless of liposome hydrodynamic diameter (0.13 and 0.28 μm) and lamellarity (unilamellar and oligolamellar). However, increases in median aerodynamic and mobility diameter, by a factor of 1.5–2, were obtained using changes in lipid mass concentration. Dye release rates were unchanged using wet aerosol collection (impingement), but increased using dry collection by impaction. This implies that drying induces changes in the liposome bilayers, which could lead to leakage of drug payload. We find that suspensions of oligolamellar liposomes are suitable for generation of submicron particles with controlled release properties, because of their larger internal volume (drug loading capacity) and lower disruption (change in dye-release rates) during aerosol generation.

Antioxidant Properties of Biohybrids Based on Liposomes and Sage Silver Nanoparticles

This paper is aimed to describe a simple and rapid eco-friendly bottom-up approach for the preparation of antioxidant silver bionanostructures using a leaf extract from sage (Salvia officinalis L.). The bioreduction property of sage in the synthesis of silver nanoparticles was investigated by UV-VIS and Attenuated Total Reflectance Fourier Transform Infrared spectroscopy. During their preparation, the particle size analysis was performed by using Dynamic Light Scattering technique. Ultrasonic irradiation was used to obtain sage silver nanoparticles. The morphology (size and shape) of the herbal silver nanoparticles was evaluated by Scanning Electron Microscopy that revealed the formation of spherical phytonanoparticles with size less than 80 nm. In order to increase their stability and their biocompatibility, the sage silver nanoparticles were introduced in two types of liposomes: soybean lecithin- and Chla-DPPC-lipid vesicles which were prepared by thin film hydration method. X-Ray Fluorescence analysis confirmed the silver presence in liposomes/sage-AgNPs biohybrids. The stability of liposomes/herbal AgNPs bioconstructs was checked by zeta potential measurements. The most stable biohybrids: Chla-DPPC/sage-AgNPs with zeta potential value of -34.2 mV, were characterized by Atomic Force Microscopy revealing the spherical and quasi-spherical shaped profiles of these nanobiohybrids with size less than 96 nm. The antioxidant activity of the silver bionanostructures was evaluated using chemiluminescence assay. The developed eco-friendly silver phytonanostructures based on lipid membranes, nanosilver and sage extract, manifest strong antioxidant properties (between 86.5% and 98.6%).

Physicochemical characterization of liposomes after ultrasound exposure – Mechanisms of drug release

Ultrasound is investigated as a novel drug delivery tool within cancer therapy. Non-thermal ultrasound treatment of solid tumours post i.v.-injection of drug-carrying liposomes may induce local drug release from the carrier followed by enhanced intracellular drug uptake. Recently, ultrasound-mediated drug release of liposomes (sonosensitivity) was shown to strongly depend on liposome membrane composition. In the current study the ultrasound-mediated drug release mechanism of liposomes was investigated. The results showed that differences in ultrasound drug release kinetics obtained for different liposomal compositions were caused by distinctive release mechanisms of the carriers. Two types of liposomes composed of 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE) and hydrogenated soy l-α-phosphatidylcholine (HSPC) as main lipids, respectively, were recently shown to vary in sonosensitivity. Here, these liposomes were analyzed prior to and after a given ultrasound-exposure for their mean size, size distribution and morphology. Cryo-transmission electron microscopy, dynamic light scattering and asymmetric flow field-flow fractionation in combination with multi-angle light scattering revealed a significant change in mean size, size distribution and morphology of DOPE-based liposomes after ultrasound, pointing to an irreversible disruption of the vesicles and concomitant drug release. In contrast, the HSPC-based liposomes remained unchanged in size and structure after ultrasound application, indicating pore-mediated release mechanisms. The results show that the release mechanisms and interactions between ultrasound and liposomes depend on the liposome membrane-composition, explaining their sonosensitive properties.

The effects of lyophilization on the physico-chemical stability of sirolimus liposomes.

The major limitation in the widespread use of liposome drug delivery system is its instability. Lyophilization is a promising approach to ensure the long-term stability of liposomes. The aim of this study was to prepare sirolimus-loaded liposomes, study their stability and investigate the effect of lyophilization either in the presence or in the absence of lyoprotectant on liposome properties. Two types of multi-lamellar liposomes, conventional and fusogenic, containing sirolimus were prepared by modified thin film hydration method with different ratio of dipalmitoylphosphatidylcholine (DPPC), cholesterol and dioleoylphosphoethanolamine (DOPE), and were lyophilized with or without dextrose as lyoprotectant. Chemical stability investigation was performed at 4°C and 25°C until 6 months using a validated HPLC method. Physical stability was studied with determination of particle size (PS) and encapsulation efficiency (EE %) of formulations through 6 months. Chemical stability test at 4°C and 25°C until 6 months showed that drug content of liposomes decreased 8.4% and 20.2% respectively. Initial mean EE % and PS were 72.8 % and 582 nm respectively. After 6 months mean EE % for suspended form, lyophilized without lyoprotectant and lyophilized with lyoprotectant were 54.8 %, 62.3% and 67.1 % at 4°C and 48.2%, 60.4 % and 66.8 % at 25°C respectively. Corresponding data for mean PS were 8229 nm, 2397 nm and 688nm at 4°C and 9362 nm, 1944 nm and 737 nm at 25°C respectively. It is concluded that lyophilization with and without dextrose could increase shelf life of liposome and dextrose has lyoprotectant effect that stabilized liposomes in the lyophilization process.

Interactions of a Photochromic Spiropyran with Liposome Model Membranes

The interactions between anionic or zwitterionic liposomes and a water-soluble, DNA-binding photochromic spiropyran are studied using UV/vis absorption and linear dichroism (LD) spectroscopy. The spectral characteristics as well as the kinetics of the thermal isomerization process in the absence and presence of the two different liposome types provide information about the environment and whether or not the spiropyran resides in the liposome membrane. By measuring LD on liposomes deformed and aligned by shear flow, further insight is obtained about interaction and binding geometry of the spiropyran at the lipid membranes. We show that the membrane interactions differ between the two types of liposomes used as well as the isomeric forms of the spiropyran photoswitch.

Relaxivities of magnetoliposomes: The effect of cholesterol

We present relaxivities measurements for both the longitudinal and transverse relaxations of two types of liposomes loaded with ultra small superparamagnetic iron oxide nanoparticles. The magnetoliposome systems presented are soybean phosphatidylcholine liposomes, with and without cholesterol, in the phospholipid bilayer with different molar ratios lipid:cholesterol. In fact, cholesterol is needed to obtain stable liposomes for intravenous administration. The longitudinal and transverse relaxivities were measured with a NMR spectrometer in a 7T magnetic field. For the studied concentrations, the liposomes show a negligible effect on the longitudinal relaxation time T1 of the medium, but they are very efficient on decreasing the transverse relaxation time T2, the behaviour one expects for a negative CA. We observed a lower transverse relaxivity for the magnetoliposome nanosystem with cholesterol, which strongly decreases with the cholesterol content in the liposome bilayer.

Comparative spectroscopic studies on liposomes containing chlorophyll a and chlorophyllide a

Chlorophyll a (Chla) and chlorophyllyde a (Chlida) - a derivative of Chla, have been incorporated in the lipid bilayers of two types of liposomes, small unilamellar vesicles (SUV) and multilamelar vesicles (MLV). The objective of the present work was to compare the spectral behaviour of Chla and Chlida incorporated in the lipid bilayers and their sensing behaviour at molecular level. The VIS absorption and fluorescence emission presented differences depending on the type of liposomes and inserted pigment, reflecting the different localization of porphyrin macrocycle in the lipid moieties. The temperature dependence of emission anisotropy and fluorescence intensity, for both Chla and Chlida incorporated in DPPC SUV, revealed the presence of different lipid phases. The degree of incorporation of quercetin (QCT) in liposome membrane was studied by using Chla and Chlida as molecular sensors. The fluorescence polarisation data and the fluorescence quenching process provided arguments for the insertion of the QCT at the interface lipid/water, in the vicinity of lipid polar heads and porphyrin macrocycle. The phytyl chain of Chla penetrating in the hydrophobic core of the lipid bilayers is responsible for the observed differences among Chla and Chlida in sensing the lipid phase transition and the fluorescence quenching process induced by QCT.

α-Hemolysin membrane pore density measured on liposomes

Membrane pore proteins are powerful tools that allow manipulation of the inside composition of micron sized bioreactors such as artificial liposomes. While the pores self-assemble very reliably on phospholipid bilayers, the determination of the number of pores in situ for liposomes remains difficult. Here we present three independent methods to establish the number of pores on different types of liposomes: (A) the loss of refractive index due to equilibration of the inside and outside buffer conditions, and the loss of volume by (B) membrane aspiration and by (C) membrane tether pulling experiments. With these three methods we are able to determine the pore density on the membrane, and all measurements give similar values; an average pore distance is found on the order of 100 nm.

Application of liposomes in drug development--focus on gastroenterological targets.

Over the past decade, liposomes became a focal point in developing drug delivery systems. New liposomes, with novel lipid molecules or conjugates, and new formulations opened possibilities for safely and efficiently treating many diseases including cancers. New types of liposomes can prolong circulation time or specifically deliver drugs to therapeutic targets. This article concentrates on current developments in liposome based drug delivery systems for treating diseases of the gastrointestinal tract. We will review different types and uses of liposomes in the development of therapeutics for gastrointestinal diseases including inflammatory bowel diseases and colorectal cancer.

Structure–transfection activity relationships in a series of novel cationic lipids with heterocyclic head-groups

Cationic liposomes are promising candidates for the delivery of various therapeutic nucleic acids. Here, we report a convenient synthesis of carbamate-type cationic lipids with various hydrophobic domains (tetradecanol, dialkylglycerol, cholesterol) and positively charged head-groups (pyridinium, N-methylimidazolium, N-methylmorpholinium) and data on the structure-transfection activity relationships. It was found that single-chain lipids possess high surface activity, which correlates with high cytotoxicity due to their ability to disrupt the cellular membrane by combined hydrophobic and electrostatic interactions. Liposomes containing these lipids also display high cytotoxicity with respect to all cell lines. Irrespective of chemical structures, all cationic lipids form liposomes with similar sizes and surface potentials. The characteristics of complexes composed of cationic liposomes and nucleic acids depend mostly on the type of nucleic acid and P/N ratios. In the case of oligodeoxyribonucleotide delivery, the transfection activity depends on the type of cationic head-group regardless of the type of hydrophobic domain: all types of cationic liposomes mediate efficient oligonucleotide transfer into 80-90% of the eukaryotic cells, and liposomes based on lipids with N-methylmorpholinium cationic head-group display the highest transfection activity. In the case of plasmid DNA and siRNA, the type of hydrophobic domain determines the transfection activity: liposomes composed of cholesterol-based lipids were the most efficient in DNA transfer, while liposomes containing glycerol-based lipids exhibited reasonable activity in siRNA delivery under serum-free conditions.

Characterisation and quantification of liposome-type nanoparticles in a beverage matrix using hydrodynamic chromatography and MALDI–TOF mass spectrometry

This paper describes the characterisation of liposome-type nanoparticles (NPs) dispersed in a beverage matrix. Characterisation is based on a two-step procedure: first, liposomes are separated on the basis of size in the nanometre range by use of hydrodynamic chromatography (HDC); second, chemical characterisation is performed by use of MALDI-TOF mass spectrometry (MS). Characterisation of three types of Coatsome liposome, a commercially available type of empty liposome, was investigated. All three liposome types, Coatsome A = anionic, N = neutral, and C = cationic, gave single peaks in HDC, reflecting diameters of 153, 187, and 205 nm, respectively. Subsequent MALDI-TOF MS in positive mode furnished major signals at m/z = 734.5 ([M + H](+) adduct) and m/z = 756.6 ([M + Na](+) adduct) of L-(α)-dipalmitoylphosphatidylcholine (DPPC) monomer and dimeric adducts at m/z = 1468.1 and m/z = 1490.1, respectively. MALDI-TOF MS in negative mode gave a signal at m/z = 721.3 ([M - H](-) adduct) of L-(α)-dipalmitoylphosphatidylglycerol (DPPG), except for Coatsome C which lacks this phospholipid. After HDC separation of Coatsome A NPs the major DPPC and DPPG signals can be detected in the expected fractions by use of MALDI-TOF MS in positive and negative modes, respectively. Validation of the analytical strategy revealed linearity (R(2) > 0.99), repeatability (relative standard deviation <10 %), and reproducibility (relative standard deviation between days <10 %) were good, recovery was 61 ± 5 %, and the limit of quantification was 1 mg mL(-1) in this matrix. With 4 mg Coatsome A mL(-1) 20 out of 20 samples furnished the 734.5 and 756.6 signals typical of DPPC in MALDI-TOF MS characterisation.

Interactions of DMPC and DMPC/gemini liposomes with the cell membrane investigated by electrorotation

The electrorotation technique was utilized to investigate the interactions between a mouse fibroblast cell line and zwitterionic liposomes formed by a natural phospholipid or cationic liposomes formulated with the same phospholipid and a cationic gemini surfactant. The application of this technique allowed an accurate characterization of the passive dielectric behavior of the plasma membrane by the determination of its specific capacitance and conductance. Changes of these parameters, upon interaction with the liposomes, are related to variations in the structure and or in the transport properties of the membrane. Cells were exposed to both types of liposomes for 1 or 4h. Electrorotation data show a dramatic reduction of the dielectric parameters of the plasma membrane after one hour treatment. After 4h of treatment the effects are still observed only in the case of the cationic liposomes. Surprisingly, these same treatments did not cause a relevant biological damage as assessed by standard viability tests. A detailed discussion to rationalize this phenomenon is presented.

Next step in drug delivery: getting to individual organelles

Next step in drug delivery: getting to individual organelles

Fliposomes: pH-triggered conformational flip of new trans-2-aminocyclohexanol-based amphiphiles causes instant cargo release in liposomes

A new type of pH-sensitive liposomes (fliposomes) was designed based on the amphiphiles that are able to perform a pH-triggered conformational flip (flipids). This flip disrupts the liposome membrane and causes rapid release of the liposome cargo, specifically in response to lowered pH. The flipids (1) and (2) are equipped with a trans-2-aminocyclohexanol conformational switch. pH-sensitive fliposomes containing one or both of these flipids, as well as POPC and PEG ceramide, were constructed and characterized. These compositions were stable at 4°C and pH 7.4 for several months. Fliposomes loaded with ANTS/DPX performed an unusually quick content release within a few seconds at pH below 8.5 (in case of 2) and 6.0 (in case of 1). This difference in pH sensitivity demonstrates a potential for the custom design of flipids by variation of the amino group to target areas with specific pH values. The pH titration curves for the fliposome leakage parallel the curves for the acid-induced conformational flip of 1 and 2 studied by 1H NMR. A plausible mechanism of pH sensitivity starts with an acid-triggered conformational flip of 1 or 2, which changes the molecular size and shape, shortens the lipid tails, and perturbs the liposome membrane, resulting in the content leakage.