Delivery of radioiodinated antisense oligonucleotides in long circulating liposomes in vivo

The anionic long circulating liposomes (ALCLs) prepared in previous studies enabled high loading efficiency, small particle size, and good stability. In addition, the uptake by tumor cells and delivery of radioiodinated antisense oligonucleotides (ASON) to MCF‐7 breast cancer cell line was improved. The liposomes also displayed valuable pharmacologic properties characterized by a long half‐life, slow clearance, and a significant area under the concentration–time curve (AUC) in vivo. This study emphasizes the contribution of ALCLs to the anti‐tumor effect of ASON and radiation therapy. Our results show that ALCLs improve biodistribution and delivery of radioiodinated ASON in tumor bearing rats, which is characterized by the suppression of tumor growth, decreased bcl‐2 expression, and increased tumor cell necrosis in the mammary tumor.     

Retention of Eucalyptol,a Natural Volatile Insecticide,in Delivery Systems Based on Hydroxypropyl‐β‐Cyclodextrin and Liposomes

Eucalyptol (Euc) is a natural monoterpene with insecticide effects. Being highly volatile and sensitive to ambient conditions, its encapsulation would enlarge its application. Euc‐loaded conventional liposomes (CL), cyclodextrin/drug inclusion complex, and drug‐in‐cyclodextrin‐in‐liposomes (DCL) are prepared to protect Euc from degradation, reduce its evaporation, and provide its controlled release. The liposomal suspension is freeze‐dried using hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) as cryoprotectant. The liposomes are characterized before and after freeze‐drying. The effect of Euc on the fluidity of liposomal membrane is also examined. A release study of Euc from delivery systems, in powder and reconstituted forms, is performed by multiple head extraction at 60 °C after 6 months of storage at 4 °C. CL and DCL suspensions are homogeneous, show nanometric vesicles size, spherical shape, and negative surface charge before and after freeze‐drying. Moreover, HP‐β‐CD does not affect the fluidity of liposomes. CL formulations present a weak encapsulation for Euc. The loading capacity of eucalyptol in DCL is 38 times higher than that in CL formulation. In addition, freeze‐dried DCL and HP‐β‐CD/Euc inclusion complex show a higher retention of eucalyptol than CL delivery system. Both carrier systems HP‐β‐CD/Euc and Euc‐loaded DCL decrease Euc evaporation and improve its retention. Practical Applications: Eucalyptol is a natural insecticide. It is highly volatile and poorly soluble in water. To enlarge its application, its encapsulation in three delivery systems (conventional liposomes, cyclodextrin/drug inclusion complex, combined system composed of cyclodextrin inclusion complex and liposome) is studied. In this paper it is proved that cyclodextrin/eucalyptol inclusion complex and eucalyptol‐in‐cyclodextrin‐in‐liposome are effective delivery systems for encalyptol encapsulation, retention, and release.     

Elaboration of Lutein-Loaded Nanoliposomes Using Supercritical CO2

A batch process for producing lutein-loaded liposomes using supercritical CO₂ is studied. The effects of the variation of pressure (10 and 15 MPa), temperature (308, 313, and 318 K), and lutein to lipid ratio (0.5 and 1 wt%) on the liposome average size and size distribution are investigated, as well as on the encapsulation efficiency (EE) of lutein. This process is worked in a repeatable manner and is allowed the production of nanoliposomes with mean diameters (MDs) ranging from 65 ± 33 to 77 ± 40 nm, obtaining lutein EEs ranging from 82.1 ± 3.7% to 91.9 ± 2.9%. Temperature, pressure, and lutein to lipid ratio seem to have no impact on size, size distribution, and EE on formed liposomes. The use of low temperatures and low pressures allows the obtainment of liposomes with diameters less than 100 nm and limits the process energy cost. Moreover, the supercritical CO₂-assisted batch process effectively encapsulates lutein into liposome, an antioxidant molecule used for the prevention of retinal damage. Liposomes formed by this supercritical process have the desired characteristics for human target delivery. Practical applications: This work on the optimization of a process for developing liposomes in a supercritical environment has applications in medicine. Indeed, the liposomes formed with this process are nanoliposomes with a size of less than 80 nm. In addition, excellent lutein EEs (hydrophobic molecules) show that the liposomes formed constitute excellent coating matrices for the protection of active ingredients. These reasons make these liposome matrices applicable in nanomedicine (injection of sensitive drugs requiring protection before injection). The elaboration process also makes it possible to form liposomes with desired properties by changing pressure, temperature, or lecithin concentration. Therefore, this work focuses on the properties of liposomes as a function of the operating conditions.     

A Comparative Study of O/W Nanoemulsions Using Extra Virgin Olive or Olive‐Pomace Oil: Impacts on Formation and Stability

Nanoemulsions are considered an innovative approach for industrial food applications. The present study explored the potential use of olive‐pomace oil (OPO) for oil‐in‐water (o/w) nanoemulsion preparations and compared the effectiveness of extra virgin olive oil (EVOO) and OPO at nanoemulsion formulations. The ternary‐phase diagrams were constructed and the o/w nanoemulsions properties were evaluated in relation to their composition. The results showed that it is possible to form OPO nanoemulsions using Polysorbate 20 or Polysorbate 40. Nanoemulsions with EVOO and OPO presented desirable properties, in terms of kinetic stability (emulsion stability index % [ESI%]), mean droplet diameter (MDD), polydispersity index (PDI), ζ‐potential, viscosity, and turbidity. EVOO exhibited lower surface and interfacial tension forming nanoemulsions with a high ESI% and a low MDD. However, OPO led to nanoemulsions with a high ESI% but with a higher MDD. It was observed that by increasing the emulsifier concentration the MDD decreased, while increasing the dispersed phase concentration led to a higher MDD and a lower ESI%. Finally, nanoemulsions with the smallest MDD (99.26 ± 4.20 nm) and PDI (0.236 ± 0.010) were formed using Polysorbate 40, which presented lower surface and interfacial tension. Specifically, the nanoemulsion with 6 wt% EVOO and 6 wt% Polysorbate 40 demonstrated an interfacial tension of 51.014 ± 0.919 mN m^?1 and an MDD of 99.26 ± 4.20 nm. However, the nanoemulsion with 6 wt% OPO and 8 wt% Polysorbate 20 presented an interfacial tension of 54.308 ± 0.089 mN m^?1 and an MDD of 340.5 ± 7.1 nm.     

Tuning Cerium(IV)‐Assisted Hydrolysis of Phosphatidylcholine Liposomes under Mildly Acidic and Neutral Conditions

With the goal of designing a lysosomal phospholipase mimic, we optimized experimental variables to enhance Ce^IV‐assisted hydrolysis of phosphatidylcholine (PC) liposomes. Our best result was obtained with the chelating agent bis–tris propane (BTP). Similar to the hydrolytic enzyme, Ce^IV‐assisted hydrolysis of PC phosphate ester bonds was higher at lysosomal pH (～4.8) compared to pH 7.2. In the presence of BTP, the average cleavage yield at ～pH 4.8 and 37 °C was: 67±1 %, 5.7‐fold higher than at ～pH 7.2 and roughly equivalent to the percent of phospholipid found on the metal‐accessible exo leaflet of small liposomes. No Ce^IV precipitation was observed. When BTP was absent, there was significant turbidity, and the amount of cleavage at ～pH 4.8 (69±1 %) was 2.1‐fold higher than the yield obtained at ～pH 7.2. Our results show that BTP generates homogenous solutions of Ce^IV that hydrolyze phosphatidylcholine with enhanced selectivity for lysosomal pH.     

Methoxy polyethylene glycol–cholesterol modified soy lecithin liposomes for poorly water-soluble anticancer drug delivery

Soy lecithin liposomes (SLP) were prepared and partially surface modified with methoxy polyethylene glycol-cholesterol conjugate (mPEG-Chol) to improve its poorly-soluble-water-anticancer-drugs delivery efficiency. Paclitaxel (PTX) was used as the model drug and the PTX/SLP@mPEG was successfully developed with the optimal mass ratio of mPEG-Chol determined at 4% in the SLP@mPEG formulation. The optimal SLP@mPEG formulation had a particle size range of 161.80 ± 1.51 nm and a negative surface charge of −54.30 ± 1.40 mV. Besides, a sustained drug release profile of 72 h and an encapsulation efficiency of 87.48 ± 0.70% was recorded. Moreover, in vitro cytotoxicity assays demonstrated that SLP@mPEG is nontoxic and cytocompatible. Overall, these obtained results provide insights into the potential of SLP@mPEG as a platform for the development of more effective therapies against cancers.     

Amino‐terminated polylactide micelles with an external poly(ethylene oxide) corona as carriers of drug‐loaded anionic liposomes

Micelles were prepared from a mixture of NH₂‐terminated poly(l ‐lactide) and poly(d ,l ‐lactide)‐block‐poly(ethylene oxide) (molar ratio of 3:7). The micelles were complexed with bilayer lipid vesicles (liposomes) composed of anionic palmitoyloleoylphosphatidylserine and zwitterionic dioleoylphosphatidylcholine in a molar ratio of 3:7. The micelles and micelle–liposome complexes were characterized using dynamic light scattering, laser electrophoresis, fluorimetry, transmission electron microscopy, enzymatic hydrolysis and cell viability with the following main findings. (i) Average diameter of micelle cores was found to be 70 ± 10 nm. (ii) Each micelle carried ca 20 000 amino groups. (iii) In a pH 7 solution the impact of the protonated NH₂ groups in the total surface of micelles was negligible owing to their screening by bulky poly(ethylene oxide) blocks. (iv) The micelles were stable in slightly acidic and neutral aqueous solutions, but aggregated in slightly alkaline solutions. (v) The micelles showed no cytotoxicity up to 0.04 mg mL^?1 concentration (the maximum concentration in the experiment). (vi) Each micelle adsorbed ca 30 anionic liposomes loaded with the antitumor antibiotic doxorubicin; the liposomes retained their integrity upon binding with micelles. (vii) The initial micelles and the micelle–liposome complexes showed two‐week stability to enzymatic hydrolysis. © 2018 Society of Chemical Industry     

Enhanced Heat Stability of α‐Chymotrypsin through Single‐Enzyme Confinement in Attoliter Liposomes

The entrapment of α‐chymotrypsin (α‐CT) within 70–140 nm liposomes formed from POPC (1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphocholine) leads to an unexpected and remarkable increase in the thermal stability of the enzyme. This finding is based on the observation that heating aqueous suspensions of α‐CT‐containing POPC liposomes to 80 °C for 30 minutes resulted in partial enzyme inactivation, whereas the same treatment of aqueous solutions of free α‐CT inactivated the enzyme completely. The stabilizing effect of enzyme confinement in the attoliter volumes of the liposomes was found to increase with decreasing numbers of α‐CT molecules per liposome. Single‐enzyme confinement was particularly effective, as intermolecular interactions between heat‐denatured α‐CT molecules (causing irreversible inactivation) are not possible.     

Transport of Glial Cell Line-Derived Neurotrophic Factor into Liposomes across the Blood-Brain Barrier: In Vitro and in Vivo Studies

Glial cell line-derived neurotrophic factor (GDNF) was encapsulated into liposomes in order to protect it from enzyme degradation in vivo and promote its permeability across the blood-brain barrier (BBB). In this study, GDNF conventional liposomes (GDNF-L) and GDNF target sterically stabilized liposomes (GDNF-SSL-T) were prepared. The average size of liposomes was below 90 nm. A primary model of BBB was established and evaluated by transendothelial electrical resistance (TEER) and permeability. This BBB model was employed to study the permeability of GDNF liposomes in vitro. The results indicated that the liposomes could enhance transport of GDNF across the BBB and GDNF-SSL-T had achieved the best transport efficacy. The distribution of GDNF liposomes was studied in vivo. Free GDNF and GDNF-L were eliminated rapidly in the circulation. GDNF-SSL-T has a prolonged circulation time in the blood and favorable brain delivery. The values of the area under the curve (AUC_{(0–1 h)}) in the brain of GDNF-SSL-T was 8.1 times and 6.8 times more than that of free GDNF and GDNF-L, respectively. These results showed that GDNF-SSL-T realized the aim of targeted delivery of therapeutic proteins to central nervous system.     

Preparation and efficacy of tumor vasculature‐targeted doxorubicin cationic liposomes coated by N‐trimethyl chitosan

Cationic liposomes (CLs) can accumulate in tumor vascular endothelial cells (VECs) to show high selective targeting ability. Therefore, chemotherapeutic agent‐loaded CLs are considered as new therapeutic vehicles to enhance the treatment efficacy. This study investigated the effect of N‐trimethyl chitosan (TMC), one of derivatives of chitosan with positive charge determined by its degree of quaternization (DQ), on preparing doxorubicin (DOX)‐loaded CLs. TMCs with various DQ, i.e., 20% (TMC20), 40% (TMC40), and 60% (TMC60) were synthesized and characterized by ¹HNMR. DOX‐loaded liposomes (DOXL) were prepared by ammonium sulfate gradients followed by TMC‐coating to obtain TMC‐coated DOXL with various positive surface charges. The morphology, size, ζ‐potential and drug release in vitro of TMC‐coated DOXL were studied compared with those of DOXL. Human umbilical vein endothelial cells (HUVECs) as cell model, the vascular targeting ability of TMC‐coated DOXL was evaluated in vitro. A solid tumor, formed by implantationmurine hepatoma cells (H₂₂) into mice, as tumor model, the tumor inhibition rate and tumor histological sections stained by HE of TMC‐coated DOXL group were researched compared with those of free DOX and DOXL group. It was found that with the increase of TMC's DQ, the positive surface charge of TMC‐coated DOXL was enhanced accordingly, which had little effect on DOX release in vitro while led to the significant increase of DOX uptake by HUVECs in vitro and the treatment effect on solid tumor in vivo. Especially, TMC‐coated DOXL showed better targeting ability to the nuclei compared with free DOX and DOXL, which could further enhance the efficacy of DOX in vivo. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Enhanced localization of anticancer drug in tumor tissue using polyethylenimine-conjugated cationic liposomes

Liposome-based drug delivery systems hold great potential for cancer therapy. However, to enhance the localization of payloads, an efficient method of systemic delivery of liposomes to tumor tissues is required. In this study, we developed cationic liposomes composed of polyethylenimine (PEI)-conjugated distearoylglycerophosphoethanolamine (DSPE) as an enhanced local drug delivery system. The particle size of DSPE-PEI liposomes was 130 ± 10 nm and the zeta potential of liposomes was increased from -25 to 30 mV by the incorporation of cationic PEI onto the liposomal membrane. Intracellular uptake of DSPE-PEI liposomes by tumor cells was 14-fold higher than that of DSPE liposomes. After intratumoral injection of liposomes into tumor-bearing mice, DSPE-PEI liposomes showed higher and sustained localization in tumor tissue compared to DSPE liposomes. Taken together, our findings suggest that DSPE-PEI liposomes have the potential to be used as effective drug carriers for enhanced intracellular uptake and localization of anticancer drugs in tumor tissue through intratumoral injection.     

Interaction Between VLDL and Phosphatidylcholine Liposomes Generates New γ-LpE-like Particles

One of the subfractions of HDL involved in reverse cholesterol transport is γ-LpE. It has been assumed that, like preβ-LpAI, it can be generated during the interaction between phosphatidylcholine liposomes and lipoproteins and can contribute to more efficient cholesterol efflux after the introduction of liposomes to plasma. However, there has been no evidence concerning what the sources of these particles in plasma might be. Here, we determined whether the interaction of phosphatidylcholine liposomes with VLDL and the subsequent conversions of particles could be a source of new γ-LpE particles. We found that the interaction between liposomes and VLDL affected its lipid and protein composition. The content of phospholipids increased (~96 %) while the content of free cholesterol and apolipoprotein E decreased in VLDL during the reaction with liposomes (~100 and ~24 %, respectively). New particles which did not contain apolipoprotein B were generated. Heterogeneous HDL-sized populations of particles were generated, containing phospholipids and apolipoprotein E as the sole apolipoprotein, with densities from 1.063 to 1.21 g/ml, either with γ-mobility on agarose gel and Stokes diameters from 8.58 to 22.07 nm or with preβ-mobility and Stokes diameters from 9.9 to 21.08 nm. The obtained results contribute to the understanding of changes in lipoproteins under the influence of phosphatidylcholine liposomes, showing the formation of new (γ-LpE)-like and (preβ-LpE)-like particles, similar in mobility and size to plasma HDL-LpE. These newly generated particles can claim a share of the antiatherogenic effects of liposomes, observed in studies both in vitro and in vivo.     

Polymeric siRNA delivery vectors: knocking down cancers with polymeric‐based gene delivery systems

One of the most promising routes for cancer therapy that has evolved over the previous decade is the use of small‐interfering RNA (siRNA) as a means of switching off genes that are responsible for tumour development. However, while siRNA and gene/antisense therapies provide alternatives to conventional chemotherapies, significant hurdles related to the delivery and efficacy of treatment must still be overcome before this technology can be used as an effective treatment for cancer and other diseases. This review highlights the issues associated with siRNA therapy in vivo, and describes the various approaches that are being explored using polymers as delivery vectors. In particular, the review focuses on targeted delivery as a means of improving efficacy of the gene therapy. © 2014 Society of Chemical Industry     

Optimized flurbiprofen cationic liposomes in situ gelling system of thermosensitive polymers for ocular delivery

A Flurbiprofen (FP) cationic liposomes in situ gelling system (CLIGS) of thermosensitive polymers was proposed; we investigated its in vitro and in vivo properties, and its potential use in ocular drug delivery was evaluated. This system, optimized via center composite design, was conceived from a combination of polymer‐ and lipid‐based delivery systems. Therefore, the system could integrate the advantages of both cationic liposomes and in situ gels and further improve the poor stability of cationic liposomes. Cationic liposomes were characterized for their particle size, shape, entrapment efficiency, ζ potential, and photograph of transmission electron microscopy. The in vitro penetration capability and precorneal retention time of the FP CLIGS were evaluated by a vertical Franz‐type cell method and γ scintigaraphy, respectively. The FP CLIGS showed an improved stability during a 30‐day storage period over than of FP cationic liposomes. In conclusion, CLIGS serves as a means to overcome a major limitation of cationic liposomes with a prolonged precorneal retention time, enhanced stability, and convenient administration due to the modified gelatinization temperature; this justifies their use as a carrier adjuvant for ocular delivery behaviors. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Delivery of the Radionuclide 131I Using Cationic Fusogenic Liposomes as Nanocarriers

Liposomes are highly biocompatible and versatile drug carriers with an increasing number of applications in the field of nuclear medicine and diagnostics. So far, only negatively charged liposomes with intercalated radiometals, e.g., ⁶⁴Cu, ^99mTc, have been reported. However, the process of cellular uptake of liposomes by endocytosis is rather slow. Cellular uptake can be accelerated by recently developed cationic liposomes, which exhibit extraordinarily high membrane fusion ability. The aim of the present study was the development of the formulation and the characterization of such cationic fusogenic liposomes with intercalated radioactive [¹³¹I]I⁻ for potential use in therapeutic applications. The epithelial human breast cancer cell line MDA-MB-231 was used as a model for invasive cancer cells and cellular uptake of [¹³¹I]I⁻ was monitored in vitro. Delivery efficiencies of cationic and neutral liposomes were compared with uptake of free iodide. The best cargo delivery efficiency (~10%) was achieved using cationic fusogenic liposomes due to their special delivery pathway of membrane fusion. Additionally, human blood cells were also incubated with cationic control liposomes and free [¹³¹I]I⁻. In these cases, iodide delivery efficiencies remained below 3%.     

Composition and properties of complexes between anionic liposomes and diblock copolymers with cationic and poly(ethylene oxide) blocks

A series of cationic diblock copolymers were synthesized via sequential anionic polymerization of 2‐vinylpyridine and ethylene oxide and further quaternization of the resulting diblock copolymers with dimethyl sulfate. Diblock copolymers with a degree of polymerization (DP) of the cationic block equal to 40 and DP of the poly(ethylene oxide) (PEO) block equal to 45, 210 and 450, as well as a cationic homopolymer with DP = 40 (control), were adsorbed on the surface of anionic liposomes of 40–60 nm in diameter. The liposomes were constructed with egg lecithin admixed with 0.1 mole fraction of a doubly anionic lipid, cardiolipin. The liposome–polymer complexes were characterized using electrophoretic mobility measurements, dynamic light scattering, conductivity, fluorescence and UV spectroscopy, and differential scanning calorimetry. Adsorption of the polymers causes the liposomes to aggregate; the only exception is the diblock copolymer with DP of the PEO block of 450, which shows an aggregation‐preventing effect. In all cases, the integrity of liposomes is retained upon their complexation with polymers. The diblock copolymer with a short PEO block induces clustering of anionic lipid in the outer leaflet of the membrane; this effect becomes less pronounced with increasing DP of the PEO block. The differences in behaviour of the diblock copolymers are explained in terms of copolymer cluster formation via hydrogen bonding between neighbouring PEO blocks. These observations are important for interpretation of biological effects produced by cationic polymers and selection of cationic polymers for biomedical applications. © 2017 Society of Chemical Industry     

PEG and PEG-peptide based doxorubicin delivery systems containing hydrazone bond

mPEG and mPEG-peptide based drug delivery systems were prepared by conjugating doxorubicin (DOX) to these carrier molecules via hydrazone bond. The peptide, AT1, with a sequence of CG₃H₆G₃E served as mPEG and doxorubicin attachment site. Histidines were incorporated to the sequence to improve pH responsiveness of the carrier molecule. Hydrodynamic diameters (mean sizes) of mPEG-based drug delivery system (mPEG-HYD-DOX) were measured as 9?±?0.5 and 7?±?0.5 nm at pH 7.4 and pH 5.0, respectively. Mean size of the aggregates of the peptide containing drug delivery system, mPEG-AT1-DOX, was determined as 12?±?2 nm at neutral pH. At pH 5.0, on the other hand, mPEG-AT1-DOX exhibited a size distribution between 20 and 100 nm centered at about 40 nm. Comparison of % DOX release values of the drug delivery systems obtained at pH 7.4 and pH 5.0 indicated that mPEG-AT1-DOX has enhanced pH sensitivity. DOX equivalent absolute IC₅₀ values were obtained as 0.96?±?0.51, 21.9?±?5.9, and 5.55?±?0.75 μg/mL for free DOX, mPEG-HYD-DOX, and mPEG-AT1-DOX, respectively. Considering more pronounced pH sensitivity and cytotoxicity of mPEG-AT1-DOX, the use of both pH responsive functional groups and acid cleavable chemical bond between the carrier molecule and drug can be a promising approach in the design of drug delivery systems for cancer therapy.     

Tamoxifen‐loaded microspheres based on mixtures of poly(D,L‐lactide‐co‐glycolide) and poly(D,L‐lactide) polymers: Effect of polymeric composition on drug release and in vitro antitumoral activity

Mixtures of different bioerosionable polyesters were used to prepare microparticulated tamoxifen delivery systems to achieve anticancer effects in breast malignant cancer cells. Tamoxifen (TMX) was included into microspheres (MS) formulated via spray‐drying. Mixtures of poly(D ,L ‐lactide‐co‐glycolide) (PLGA) of different lactide/glycolide proportions (50 : 50 and 75 : 25) and poly(D ,L ‐lactic acid) (PLA) were used. The average diameter of the resultant TMX‐loaded microparticles was in the range 1.04 ± 0.51–1.55 ± 0.95 μm. The encapsulation efficiency of TMX was between 97.8% [48.9 ± 0.1 TMX (μg)/MS (mg)] and 69.6% [36.6 ± 0.1 TMX (μg)/MS (mg)] depending on the polymeric composition of the formulation. Drug burst effect was not observed. TMX was released from the polymeric matrices in a sustained release manner between 11 and 58 days depending on polymeric composition of microspheres. TMX‐loaded microspheres showed high efficacy in causing cell death in MCF7 breast malignant cancer cells. Thus, these TMX‐loaded PLGA‐based microspheres hold potential to treat breast malignant cancer cells. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Gene Delivery by Liposomes

In gene therapy, genetic materials, such as plasmid DNA, antisense oligonucleotides (asODNs), and small interfering RNA (siRNA), can be used to treat or prevent disease. This includes replacing a mutated gene, inactivating a mutated gene, or introducing a new gene. Although gene therapy is a promising treatment option for a number of diseases (including inherited disorders, some types of cancer, and certain viral infections), successful gene therapy is hampered by the lack of effective delivery systems (viral and nonviral). There are several nonviral gene carriers, such as lipids, polymers, and peptides, that can be used for this purpose. Liposomal delivery of nucleic acids, such as plasmid DNA, asODNs, and siRNAs, represents a very promising nanocarrier system that is relatively safe and effective in delivering genes to targeted locations in the body. Lipoid-based delivery systems have also been shown to be stable in serum and plasma, have improved biodistribution, prolonged circulation half-life, and enhanced target tissue selectivity. The most common lipids used in liposomes are cationic lipids, which facilitate binding between their positively charged head group(s) to negatively charged nucleic acids. This review is focused on the most common methods of lipoid-based nanocarriers of nucleic acids for gene therapy in vivo.     

Synthesis and Characterization of Amphiphilic Gd(III) Complexes: Gd‐DTPA‐BA

Magnetic resonance imaging (MRI) is widely used to identify different diseases. MRI contrast agents, used to enhance the MRI signal, have been studied extensively for precise diagnosis. Based on the advantages of macromolecular MRI contrast agents of higher contrast imaging ability and a longer cycle time, this article modified the most common micromolecular contrast agent (Gd‐diethylene triamine pentaacetic acid [DTPA]). 2 long saturated aliphatic chains were attached to both sides of DTPA. DTPA derivatives with 12, 14, and 16 carbon lengths were synthesized and chelated to Gd³⁺. 3 amphiphilic MRI contrast agents were obtained and their structures were characterized using mass spectrometry, ¹H NMR, and Fourier transform infrared. Furthermore, the surface tension of the compounds was measured, and liposomes were prepared by mixing the synthesized amphiphilic molecules with egg lecithin and cholesterol. The assembly behavior of the liposomes was studied using transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential measurements. TEM showed that the liposomes possessed bilayer vesicle structures. The liposome size distribution determined by DLS was from 10 to 1000 nm, and as the aliphatic chain length increased, the polydispersity index (PDI) and zeta potential increased. No obvious changes in the PDI and zeta potential of the liposomes were observed after 5 days at room temperature, suggesting that they possess good stability.