Liposomal Particles Research Articles

A Supercritical Fluid-Based Process for the Production of Fluorescein-Loaded Liposomes

Fluorescein is a synthetic dye used as a marker to monitor the absorption of liposomes into tissues, but its efficient entrapment is still challenging. In this work, we apply a supercritical fluid process that allows the production of liposomes with a high drug encapsulation efficiency. The effects of operating parameters such as the diameter of the injector, the concentration of phospholipids, and the concentration of fluorescein were studied. Liposomes with mean diameters down to ∼300 nm were obtained with fluorescein encapsulation efficiencies of ≤96%. In detail, the increase in the concentration of phospholipids produced a relative increase in liposome mean diameter and particle size distribution width. With an increase in fluorescein theoretical loading, instead, a reduction in liposome mean diameters and standard deviation was obtained. Smaller liposomes were produced using smaller injector diameters; however, the reduction of the injector diameter from 80 to 40 μm caused a reduction in the fluoresc...

Magnetic Liposomal Particles for Magnetic Imaging, Sensing, and the pH‐Sensitive Delivery of Therapeutics

Magnetic Liposomal Particles for Magnetic Imaging, Sensing, and the pH‐Sensitive Delivery of Therapeutics

Cytotoxicity of Nanoliposomal Cisplatin Coated with Synthesized Methoxypolyethylene Glycol Propionaldehyde in Human Ovarian Cancer Cell Line A2780CP

Purpose: To evaluate the cytotoxicity of pegylated nanoliposomal cisplatin on human ovarian cancer cell line A2780CP.Methods: Synthesized methoxypolyethylene glycol (mPEG) propionaldehyde was characterized by 1Hnuclear magnetic resonance (1H-NMR) and Fourier transform infrared spectroscopy (FTIR) and used as coating agent for the preparation of liposomal nanodrug formulation by reverse phase evaporation method. The characteristics of the nanoparticles were evaluated by dynamic light scattering (DLS) and scanning electron microscopy (SEM). Encapsulation efficiency was determined spectrometrically at 214.42 nm by inductively coupled plasma spectroscopy (ICP-OES). The cytotoxicity of both pegylated nanoliposomal and free cisplatin were evaluated by 3- [4, 5 dimethyl-2-thiazolyl] -2, 5- diphenyltetrazolium bromide (MTT) assay and expressed as half-maximal inhibitory concentration (IC50).Results: The mean diameter and zeta potential of drug-loaded liposomal particles and empty nanoliposomes were 125 ± 2.9 nm and -16.6 mV, 108 ± 2.2 nm and -27.2 mV, respectively, while the cytotoxicity (IC50) of free cisplatin and nanodrug formulation were 93.6 ± 3.1 μg/mL and 67.8 ± 2.3 μg/mL, respectively. In vitro toxicological results indicate that the formulation exhibited approximately 1.4-fold cytotoxicity compared with the free drug. Drug encapsulation efficiency of the nanoliposomes was approximately 98 ± 1 %.Conclusion: The findings show that the cytotoxicity of pegylated nanoliposomal cisplatin is higher than that of free cisplatin in human ovarian cancer cell line A2780CP. In vivo studies are, however, required to ascertain its therapeutic potentials.Keywords: Liposome, Nanodrug, Ovarian cancer, Polyethylene glycol, Cisplatin, Drug delivery, Cytotoxicity

Uji Aktivitas Antiproliferasi Formula Liposom Ekstrak Etanol Kunyit (Curcuma domestica) Terhadap Sel Kanker Payudara T47D

Breast cancer is one of deadliest diseases in the world. Turmeric extract was known to have antiproliferative activity. To minimize its toxicity, turmeric extract was encapsulated with liposome, a vesicle lipid bilayer that was functioned as cancer drug carrier in body. This research aimed to determine encapsulation effect of turmeric extract against antiproliferative activity in T47D breast cancer cells through in vitro assay. Liposomes was made using thin layer method and particle size was reduced by extrusion. Materials that was used phosphatidylcholine, cholesterol, and turmeric extract. Optimization of liposomes was made in three formulations with different extract concentrations. The most optimal formulation was formulation with less extract and physical parameters which have smallest precipitates and longest settling time. Evaluation liposome particle size and zeta potential were used DLS, morphology was used TEM, and entrapment efficiency was used dialysis. The most optimal formulation was tested their antiproliferative activity compared with not encapsulated extracts used 3-(4,5-dimethylazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The result showed that there was antiproliferative activity in encapsulated extracts. IC50 encapsulated extracts was 45.762 μg/ml and IC50 extracts was 36.399 μg/ml. Liposome particle size was below 445 nm. Zeta potential was -7.51 mV. Morphology was LUV and MVV. Entrapment efficiency was 63.80%. It could be concluded that encapsulation of turmeric extract into liposome could reduce its toxicity against cancer cells.

Highly Efficient Encapsulation of Anionic Small Molecules in Asymmetric Liposome Particles

Anionic small molecules are hard to penetrate the cell membranes because of their negative charges. Encapsulation of small molecules into liposome particles can provide target specific delivery of them. In our previous study, siRNA could be efficiently encapsulated into liposome particles using an asymmetric preparation method of liposomes. In this study, the same method was applied for encapsulation of small anionic fluorescent chemicals such as calcein and indocyanine green (ICG). More than 90% fluorescent chemicals were encapsulated in the asymmetric liposome particles (ALPs). No intracellular fluorescent signal was observed in the tumor cells treated with the unmodified calcein/ALPs and ICG/ALPs, whereas the surface modification with a cell-penetrating polyarginine peptide (R8 or R12) allows cellular uptake of the ALPs. The results demonstrate that the ALPs encapsulating small anionic drugs will be useful for target-specific delivery after modification of target-specific ligands.

An efficient liposome based method for antioxidants encapsulation

Apigenin is an antioxidant that has shown a preventive activity against different cancer and cardiovascular disorders. In this study, we encapsulate apigenin with liposome to tackle the issue of its poor bioavailability and low stability. Apigenin loaded liposomes are fabricated with food-grade rapeseed lecithin in an aqueous medium in absence of any organic solvent. The liposome particle characteristics, such as particle size and polydispersity are optimised by tuning ultrasonic processing parameters. In addition, to measure the liposome encapsulation efficiency accurately, we establish a unique high-performance liquid chromatography technique in which an alkaline buffer mobile phase is used to prevent apigenin precipitation in the column;. salt is added to separate lipid particles from the aqeuous phase. Our results demonstrate that apigenin encapsulation efficiency is nearly 98% that is remarkably higher than any other reported value for encapsulation of this compound. In addition, the average particle size of these liposomes is 158.9±6.1nm that is suitable for the formulation of many food products, such as fortified fruit juice. The encapsulation method developed in this study, therefore have a high potential for the production of innovative, functional foods or nutraceutical products.

Liposome Formation Using a Coaxial Turbulent Jet in Co-Flow.

Liposomes are robust drug delivery systems that have been developed into FDA-approved drug products for several pharmaceutical indications. Direct control in producing liposomes of a particular particle size and particle size distribution is extremely important since liposome size may impact cellular uptake and biodistribution. A device consisting of an injection-port was fabricated to form a coaxial turbulent jet in co-flow that produces liposomes via the ethanol injection method. By altering the injection-port dimensions and flow rates, a fluid flow profile (i.e., flow velocity ratio vs. Reynolds number) was plotted and associated with the polydispersity index of liposomes. Certain flow conditions produced unilamellar, monodispersed liposomes and the mean particle size was controllable from 25 up to >465nm. The mean liposome size is highly dependent on the Reynolds number of the mixed ethanol/aqueous phase and independent of the flow velocity ratio. The significance of this work is that the Reynolds number is predictive of the liposome particle size, independent of the injection-port dimensions. In addition, a new model describing liposome formation is outlined. The significance of the model is that it relates fluid dynamic properties and lipid-molecule physical properties to the final liposome size.

Improving lithium carbonate therapeutics by pegylated liposomal technology: an in vivo study

Bipolar disorder is a chronic mental illness which is associated with high risk of self-harm and suicide. Lithium carbonate has been suggested as a medicine to control and cure this disease. To overcome the complications related to taking lithium carbonate, nanotechnology has come to the aid of scientists. In this study, pegylated liposomal lithium carbonate nanoparticles were prepared by the reverse phase evaporation method to improve the drug’s therapeutic characteristics as well as lessening its side effects. In order to synthesize pegylated liposomal lithium carbonate, phosphatidylcholine, polyethylene glycol 3350 (PEG3350), cholesterol, and lithium carbonate were mixed. The characterization of synthesized nanoparticles was determined by Zetasizer. Encapsulation and drug loading efficiency and release pattern studies were determined through spectrophotometry method. In addition, serum lithium and creatinine levels of the samples were analyzed. The mean diameter, size distribution, and zeta potential for pegylated liposomal particles containing lithium carbonate and blank pegylated liposomal were determined by Zetasizer equal to 102 nm, 0.458, and −25.1 mV; 284.2 nm, 0.427, and −28.3 mV, respectively. Drug loading and encapsulation efficiency were calculated to be 32.87 and 97.4 %, respectively. The drug release pattern demonstrated that the half-life of the nanodrug was approximately two times higher than the standard drug. The results related to the analysis of serum lithium and creatinine levels indicated that the efficiency of liposomal drug formulation was increased compared to the standard drug. Based on the findings, the nanodrug enjoyed a half-life two times higher than that of the standard drug and an efficiency level equal to it.

Obatoclax is a direct and potent antagonist of membrane-restricted Mcl-1 and is synthetic lethal with treatment that induces Bim.

BackgroundObatoclax is a clinical stage drug candidate that has been proposed to target and inhibit prosurvival members of the Bcl-2 family, and thereby contribute to cancer cell lethality. The insolubility of this compound, however, has precluded the use of many classical drug-target interaction assays for its study. Thus, a direct demonstration of the proposed mechanism of action, and preferences for individual Bcl-2 family members, remain to be established.MethodsEmploying modified proteins and lipids, we recapitulated the constitutive association and topology of mitochondrial outer membrane Mcl-1 and Bak in synthetic large unilamellar liposomes, and measured bakdependent bilayer permeability. Additionally, cellular and tumor models, dependent on Mcl-1 for survival, were employed.ResultsWe show that regulation of bilayer permeabilization by the tBid – Mcl-1 - Bak axis closely resemblesthe tBid - Bcl-XL - Bax model. Obatoclax rapidly and completely partitioned into liposomal lipid but also rapidly exchanged between liposome particles. In this system, obatoclax was found to be a direct and potent antagonist of liposome-bound Mcl-1 but not of liposome-bound Bcl-XL, and did not directly influence Bak. A 2.5 molar excess of obatoclax relative to Mcl-1 overcame Mcl-1-mediated inhibition of tBid-Bak activation. Similar results were found for induction of Bak oligomers by Bim. Obatoclax exhibited potent lethality in a cellmodel dependent on Mcl-1 for viability but not in cells dependent on Bcl-XL. Molecular modeling predicts that the 3-methoxy moiety of obatoclax penetrates into the P2 pocket of the BH3 binding site of Mcl-1. A desmethoxy derivative of obatoclax failed to inhibit Mcl-1 in proteoliposomes and did not kill cells whose survival depends on Mcl-1. Systemic treatment of mice bearing Tsc2+/- Em-myc lymphomas (whose cells depend on Mcl-1 for survival) with obatoclax conferred a survival advantage compared to vehicle alone (median 31 days vs 22 days, respectively; p=0.003). In an Akt-lymphoma mouse model, the anti-tumor effects of obatoclax synergized with doxorubicin. Finally, treatment of the multiple myeloma KMS11 cell model (dependent on Mcl-1 for survival) with dexamethasone induced Bim and Bim-dependent lethality. As predicted for an Mcl-1 antagonist, obatoclax and dexamethasone were synergistic in this model.ConclusionsTaken together, these findings indicate that obatoclax is a potent antagonist of membranerestricted Mcl-1. Obatoclax represents an attractive chemical series to generate second generation Mcl-1 inhibitors.

Encapsulation of elderberry extract into phospholipid nanoparticles

The aim of the work was to compare the suitability of different lecithins for nanoencapsulation of elderberry extract in liposomes for the purpose of food enrichment. Lecithins extracted from egg yolk, soybean and sunflower were tested. Vesicles were prepared by thin lipid film hydration technique followed by freeze and thaw procedure. Liposomal particles were separated from unencapsulated material by gel permeation chromatography. Encapsulation efficiency, zeta potential, as well as size distribution were determined for the liposome characterization. Moreover, flow cytometry was used to examine the diversity of structure in liposome populations. It was found that all of the three tested lecithins were proper for encapsulation of elderberry extract into liposomes. Soybean lecithin proved to be the material with the best stability for the formation of liposomes. The zeta potential absolute value of those nanocapsules was the highest (−36.4mV), and their Z-average size (205nm) was the smallest. Encapsulation efficiency in this case was of 25%. Moreover, population of soybean lecithin liposomes was the most uniform both in terms of size and structure. By using both sunflower and egg yolk lecithins significantly higher encapsulation efficiency could be achieved, however those liposomes were less stable. Moreover their populations were more diverse both in terms of size and structure.

Fast and efficient detection of tuberculosis antigens using liposome encapsulated secretory proteins of Mycobacterium tuberculosis.

A rapid and efficient diagnostic test was developed for the detection of Mycobacterium tuberculosis antigens in serum samples of active tuberculosis (TB) and extrapulmonary TB patients via a liposomal agglutination-based method. A rapid card test has been developed to facilitate the recognition of high-affinity binding rabbit raised purified culture filtrate protein antibodies coupled on the surface of activated liposomal preparation. In the presence of TB antigens, the polyclonal antibodies bound to the liposomal particles demonstrate a visible agglutination reaction. The developed assay was simple, rapid, reliable, sensitive, and specific as a diagnostic test for the detection of antigens in serum samples of clinically confirmed cases of TB within 4-5 minutes' duration. The test was evaluated at different hospitals, medical colleges, and pathology centers, and involved 1483 participants. This investigation was conducted to detect the presence of these antigens during the period of active growth of the microorganism in serum samples for pulmonary TB and processed tissue biopsy for other extrapulmonary TB. Results obtained using this test were compared with acid-fast bacilli smear and culture results. Our study demonstrated that the newly developed liposome tuberculosis antigen card test detected antigens in our study population with approximately 97.48% sensitivity and 95.79% specificity. This is the first study to report the liposomal encapsulation of culture filtrate proteins from M. tuberculosis for diagnostic application.

Preparation and characterisation of nanoliposomes containing winged bean seeds bioactive peptides

The aim of this study was to produce and characterise nanosize liposomes containing bioactive peptides with antioxidative and ACE-inhibitory properties, derived from winged bean seeds (WBS) protein. WBS powder was papain-proteolysed, at 70 °C and pH 6.5 for six hours, followed by encapsulation via a solvent-free heating method. The results showed that the WBS proteolysate was successfully incorporated into spherical, unilamellar liposomal particles, with particle diameter, polydispersity index, zeta potential and encapsulation efficiency of 193.3 ± 0.12 nm, 0.4 ± 0.02 (unit less), −70.5 ± 0.30 mV and 27.6 ± 1.17%, respectively. It also demonstrated good storage stability over eight weeks at 4 °C, indicated by slight increment (15.1%) in particle size and a zeta potential only weaker by 17.2% at the end of the study period. These results suggested the feasibility of entrapping water soluble peptides in hydrophobic liposomal system that, upon optimisation, has the potential to act as bioactive food ingredient.

High resolution particle characterization to expedite development and regulatory acceptance of nanomedicines.

The pharmaceutical industry as well as European and US governing agencies have indicated the need for more accurate, high resolution, characterization of complex drug materials, nanomedicines, to facilitate their development and eventual approval. In particular, accurately measuring the size, zeta-potential, and concentration of nanomedicines is desired. Herein we demonstrate the comprehensive and high resolution analysis capabilities of tunable resistive pulse sensing (TRPS) on the most widely approved nanomedicines to-date, liposomal particles. The number-based size distribution, concentration and volume fraction of liposomes formed by extrusion through a 100 nm or 200 nm Nucleopore filter membrane are shown as well as how freeze-thaw aggregation changes individual liposomes and the overall size distribution. In addition, the simultaneous size and zeta-potential analysis capabilities of TRPS is used to characterize the homogeneity and difference between liposomes made with and without the addition of PEGylated phospholipids.

Correlating liposomal adjuvant characteristics to in-vivo cell-mediated immunity using a novel Mycobacterium tuberculosis fusion protein: a multivariate analysis study.

In this study, we have used a chemometrics-based method to correlate key liposomal adjuvant attributes with in-vivo immune responses based on multivariate analysis. The liposomal adjuvant composed of the cationic lipid dimethyldioctadecylammonium bromide (DDA) and trehalose 6,6-dibehenate (TDB) was modified with 1,2-distearoyl-sn-glycero-3-phosphocholine at a range of mol% ratios, and the main liposomal characteristics (liposome size and zeta potential) was measured along with their immunological performance as an adjuvant for the novel, postexposure fusion tuberculosis vaccine, Ag85B-ESAT-6-Rv2660c (H56 vaccine). Partial least square regression analysis was applied to correlate and cluster liposomal adjuvants particle characteristics with in-vivo derived immunological performances (IgG, IgG1, IgG2b, spleen proliferation, IL-2, IL-5, IL-6, IL-10, IFN-γ). While a range of factors varied in the formulations, decreasing the 1,2-distearoyl-sn-glycero-3-phosphocholine content (and subsequent zeta potential) together built the strongest variables in the model. Enhanced DDA and TDB content (and subsequent zeta potential) stimulated a response skewed towards a cell mediated immunity, with the model identifying correlations with IFN-γ, IL-2 and IL-6. This study demonstrates the application of chemometrics-based correlations and clustering, which can inform liposomal adjuvant design.

Synthesis of highly dispersed nanoscaled CoQ10 liposome by supercritical fluid

The nanoscaled CoQ10 liposome were synthesized by Rapid Expansion of Supercritical Solutions (RESS). Transmission electron microscopy (TEM) was used to characterize the particle size of CoQ10 liposome, and the UV spectrum was employed to evaluate the product׳s trapping efficiency. A series of CoQ10 liposome samples were synthesized by RESS under different pressures. The trapping efficiency of the CoQ10 liposome was up to 90% when the enduring pressure was at 200–300bar, but the trapping efficiency was distinctly decreased when the enduring pressure is lower than 200bar or higher than 300bar. The high resolution TEM images exhibited that the particle size of CoQ10 liposome was only 20–40nm, probably because CO2 molecules act as the membranes between the CoQ10 liposome particles in this process, which prevent the agglomeration of liposome with each other.

α, ω-Cholesterol-functionalized low molecular weight polyethylene glycol as a novel modifier of cationic liposomes for gene delivery.

Here, three novel cholesterol (Ch)/low molecular weight polyethylene glycol (PEG) conjugates, termed α, ω-cholesterol-functionalized PEG (Ch2-PEGn), were successfully synthesized using three kinds of PEG with different average molecular weight (PEG600, PEG1000 and PEG2000). The purpose of the study was to investigate the potential application of novel cationic liposomes (Ch2-PEGn-CLs) containing Ch2-PEGn in gene delivery. The introduction of Ch2-PEGn affected both the particle size and zeta potential of cationic liposomes. Ch2-PEG2000 effectively compressed liposomal particles and Ch2-PEG2000-CLs were of the smallest size. Ch2-PEG1000 and Ch2-PEG2000 significantly decreased zeta potentials of Ch2-PEGn-CLs, while Ch2-PEG600 did not alter the zeta potential due to the short PEG chain. Moreover, the in vitro gene transfection efficiencies mediated by different Ch2-PEGn-CLs also differed, in which Ch2-PEG600-CLs achieved the strongest GFP expression than Ch2-PEG1000-CLs and Ch2-PEG2000-CLs in SKOV-3 cells. The gene delivery efficacy of Ch2-PEGn-CLs was further examined by addition of a targeting moiety (folate ligand) in both folate-receptor (FR) overexpressing SKOV-3 cells and A549 cells with low expression of FR. For Ch2-PEG1000-CLs and Ch2-PEG2000-CLs, higher molar ratios of folate ligand resulted in enhanced transfection efficacies, but Ch2-PEG600-CLs had no similar in contrast. Additionally, MTT assay proved the reduced cytotoxicities of cationic liposomes after modification by Ch2-PEGn. These findings provide important insights into the effects of Ch2-PEGn on cationic liposomes for delivering genes, which would be beneficial for the development of Ch2-PEGn-CLs-based gene delivery system.

The pharmacokinetics of Zr-89 labeled liposomes over extended periods in a murine tumor model

89Zr (t1/2=78.4h), a positron-emitting metal, has been exploited for PET studies of antibodies because of its relatively long decay time and facile labeling procedures. Here, we used 89Zr to evaluate the pharmacokinetics of long-circulating liposomes over 168h (1week). We first developed a liposomal-labeling method using p-isothiocyanatobenzyl-desferrioxamine (df-Bz-NCS) and df-PEG1k-DSPE. Df-Bz-NCS was conjugated to 1mol% amino- and amino-PEG2k-DSPE, where the 1mol% df-PEG1k-DSPE was incorporated when the liposomes were formulated. Incubation of 89Zr with df, df-PEG1k, and df-PEG2k liposomes for one hour resulted in greater than 68% decay-corrected yield. The loss of the 89Zr label from liposomes after incubation in 50% human serum for 48h ranged from ~1 to 3% across the three formulations. Tail vein administration of the three liposomal formulations in NDL tumor-bearing mice showed that the 89Zr label at the end of the PEG2k brush was retained in the tumor, liver, spleen and whole body for a longer time interval than 89Zr labels located under the PEG2k brush. The blood clearance rate of all three liposomal formulations was similar. Overall, the results indicate that the location of the 89Zr label altered the clearance rate of intracellularly-trapped radioactivity and that df-PEG1k-DSPE provides a stable chelation site for liposomal or lipid-based particle studies over extended periods of time.

Outcomes analysis of an alternative formulation of PEGylated liposomal doxorubicin in recurrent epithelial ovarian carcinoma during the drug shortage era.

BackgroundIn response to the critical shortage of Doxil®, the US Food and Drug Administration (FDA) allowed temporary importation of non-FDA-approved second-generation liposomal doxorubicin, Lipo-Dox®. Lipo-Dox utilizes a different liposomal particle than Doxil and demonstrates different pharmacokinetic properties. Its use has never been evaluated in a North American population. The objective of this study was to evaluate the efficacy and tolerability of Lipo-Dox at Magee-Womens Hospital, University of Pittsburgh Medical Center, for patients with recurrent epithelial ovarian cancer who were treated during the Doxil shortage.MethodsPatients treated with Lipo-Dox from January 2012 to December 2012 were identified retrospectively. Disease response was defined radiographically by RECIST (Response Evaluation Criteria in Solid Tumors) or biochemically by CA-125 level if measurable disease was not present. Survival was defined from the start date of Lipo-Dox until the date of progression or death. Toxicity was assessed by the Gynecologic Oncology Group common toxicity criteria.ResultsEighteen patients with recurrent epithelial ovarian cancer who received Lipo-Dox were identified. These patients had a median of three prior treatment regimens. The median number of Lipo-Dox cycles given was 3.5 (range 1–8). No patients had a complete or partial response. Two patients had stable disease over a mean follow-up of 144.5 days. Fourteen patients had progressive disease, with a median time to progression of 82 days. Progression was based on CA-125 in four patients and RECIST in the remainder. Nine patients died from the disease.ConclusionAlthough this represents a small, pretreated population, there were no clinical responses to Lipo-Dox, raising the question as to whether it is an equivalent substitute for Doxil. Further evaluation is needed, but if confirmed, these findings raise concerns regarding the use of current stocks of Lipo-Dox, as well as the prudence of managing future drug shortages with pharmacologically similar, but clinically untested drugs.

Superoxide dismutase enzymosomes: carrier capacity optimization, in vivo behaviour and therapeutic activity.

A strategy not usually used to improve carrier-mediated delivery of therapeutic enzymes is the attachment of the enzymes to the outer surface of liposomes. The aim of our work was to design a new type of enzymosomes with a sufficient surface-exposed enzyme load while preserving the structural integrity of the liposomal particles and activity of the enzyme. The therapeutic antioxidant enzyme superoxide dismutase (SOD) was covalently attached to the distal terminus of polyethylene glycol (PEG) polymer chains, located at the surface of lipid vesicles, to obtain SOD-enzymosomes. The in vivo fate of the optimized SOD-enzymosomes showed that SOD attachment at the end of the activated PEG slightly reduced the residence time of the liposome particles in the bloodstream after IV administration. The biodistribution studies showed that SOD-enzymosomes had a similar organ distribution profile to liposomes with SOD encapsulated in their aqueous interior (SOD-liposomes). SOD-enzymosomes showed earlier therapeutic activity than both SOD-liposomes and free SOD in rat adjuvant arthritis. SOD-enzymosomes, unlike SOD-liposomes, have a therapeutic effect, decreasing liver damage in a rat liver ischemia/reperfusion model. SOD-enzymosomes were shown to be a new and successful therapeutic approach to oxidative stress-associated inflammatory situations/diseases.

A nanoparticle-based combination chemotherapy delivery system for enhanced tumor killing by dynamic rewiring of signaling pathways.

Exposure to the EGFR (epidermal growth factor receptor) inhibitor erlotinib promotes the dynamic rewiring of apoptotic pathways, which sensitizes cells within a specific period to subsequent exposure to the DNA-damaging agent doxorubicin. A critical challenge for translating this therapeutic network rewiring into clinical practice is the design of optimal drug delivery systems. We report the generation of a nanoparticle delivery vehicle that contained more than one therapeutic agent and produced a controlled sequence of drug release. Liposomes, representing the first clinically approved nanomedicine systems, are well-characterized, simple, and versatile platforms for the manufacture of functional and tunable drug carriers. Using the hydrophobic and hydrophilic compartments of liposomes, we effectively incorporated both hydrophobic (erlotinib) and hydrophilic (doxorubicin) small molecules, through which we achieved the desired time sequence of drug release. We also coated the liposomes with folate to facilitate targeting to cancer cells. When compared to the time-staggered application of individual drugs, staggered release from tumor-targeted single liposomal particles enhanced dynamic rewiring of apoptotic signaling pathways, resulting in improved tumor cell killing in culture and tumor shrinkage in animal models.