Interaction Of Liposomes Research Articles

Optimization of Cell Membrane Purification for the Preparation and Characterization of Cell Membrane Liposomes.

Cell membrane nanoparticles have attracted increasing interest in nanomedicine because they allow to exploit the complexity of cell membrane interactions for drug delivery. Several methods are used to obtain plasma membrane to generate cell membrane nanoparticles. Here, an optimized method combining nitrogen cavitation in isotonic buffer and sucrose gradient fractionation is presented. The method allows to obtain cell membrane fractions of high purity from both suspension and adherent cells. Comparison with other common methods for membrane extraction, where mechanical lysis using cell homogenizers is performed in isotonic or hypotonic buffers, shows that the optimized procedure yields high purity membrane in a robust and reproducible way. Procedures to mix the purified membrane with synthetic lipids to obtain cell membrane liposomes (CMLs) are presented and indications on how to optimize these steps are provided. CMLs made using crude membrane isolates or the purified membrane fractions show different uptake by cells. The CMLs made with the optimized procedure and liposomes of the same composition but without cell membrane components are thoroughly characterized and compared for their size, zeta potential, bilayer and mechanical properties to confirm membrane protein inclusion in the CMLs. Cell uptake studies confirm that the inclusion of membrane components modifies liposome interactions with cells.

Electroformation and characterization of soybean protein isolate hydrolysates-modified liposomes

This research aimed to elucidate the application and feasibility of the enhancement of liposome oxidative stability by the interaction of liposomes with soybean protein isolate hydrolysates (SPIHs) during liposome electroformation. It was observed that the degree of hydrolysis, percentage of low-molecular-weight distribution, and solubility of SPIHs after enzymatic hydrolysis increased with the extension of reaction time. The average fluorescence intensity (average gray level) was approximately 200 a.u. for each liposome, indicating a homogeneous distribution of SPIHs on the liposome surface. Moreover, it was found that the advanced structure of SPIHs incorporated with liposomes was altered appreciably. Both hydrophobic forces and hydrogen bonds exhibited an important role in the interaction between SPIHs and liposomes. In addition, morphology observation indicated that the liposomes were spherical and exhibited a more compact structure after coating with SPIHs. Subsequent flow cytometry analysis showed that the diameter and number of vesicles would increase due to vesicles rupturing or reorganizing after phospholipid oxidation during the electroformation of liposomes to produce SPIHs-liposomes. While the phospholipid oxidation level of the original liposomes was 42.13%, the phospholipid oxidation level of SPIHs-liposomes did not exceed 25%, indicating that the optimal balance between electroformation parameters and phospholipid oxidation level was obtained. These results may provide novel insight into the implications of SPIHs-modified liposomes as functional additives.

DNA Origami Vesicle Sensors with Triggered Single-Molecule Cargo Transfer.

Interacting with living systems typically involves the ability to address lipid membranes of cellular systems. The first step of interaction of a nanorobot with a cell will thus be the detection of binding to a lipid membrane. Utilizing DNA origami, we engineered a biosensor with single-molecule Fluorescence Resonance Energy Transfer (smFRET) as transduction mechanism for precise lipid vesicle detection and cargo delivery. The system hinges on a hydrophobic ATTO647N modified single-stranded DNA (ssDNA) leash, protruding from a DNA origami nanostructure. In a vesicle-free environment, the ssDNA coils, ensuring high FRET efficiency. Upon vesicle binding to cholesterol anchors on the DNA origami, hydrophobic ATTO647N induces the ssDNA to stretch towards the lipid bilayer, reducing FRET efficiency. As the next step, the sensing strand serves as molecular cargo that can be transferred to the vesicle through a triggered strand displacement reaction. Depending on the number of cholesterols on the displacer strands, we either induce a diffusive release of the fluorescent load towards neighboring vesicles or a stoichiometric release of a single cargo-unit to the vesicle on the nanosensor. Ultimately, our multi-functional liposome interaction and detection platform opens up pathways for innovative biosensing applications and controllable stoichiometric loading of vesicles with single-molecule control.

A simple chemiluminescent method for the quantification of exosomes based on horseradish peroxidase adsorbed on two-dimensional nanomaterials

The development of simple methods for the isolation and quantification of exosomes in biological samples is important. By using the typical two-dimensional (2D) nanomaterials, graphene oxide (GO), the present work first studied the interaction of liposomes with the nanocomposites formed by adsorbing HRP on the GO surface and found the presence of liposomes led to the release of HRP from the GO surface to the solution phase triggering the luminol-H2O2 chemiluminescence (CL) reaction to emit light. Benefiting from the similarity of exosomes to liposomes in both composition and morphology aspects, the GO-HRP nanocomposites with a mass ratio of 120:1 and 160:1 were employed for the quantitative detection of exosomes in 100-fold diluted serum samples. The whole detection process took about 15 min and as low as 3.2 × 102 particles μL−1 of exosomes could be sensitively detected. In addition to GO-HRP nanocomposites, the CL responses of other nanocomposites obtained from adsorbing HRP on other 2D nanomaterials such as layered MoS2 for exosomes were also tested. MoS2-HRP exhibited similar behavior and the LODs for the detection of exosomes were 5.8 × 102 particles μL−1. The proposed assays were a biomarker-independent quantitative method that achieved the quantification of exosomes in serum samples directly without an isolation process.

Benefits of Combined Fluorescence Lifetime Imaging Microscopy and Fluorescence Correlation Spectroscopy for Biomedical Studies Demonstrated by Using a Liposome Model System

Drug delivery systems play a pivotal role in targeted pharmaceutical transport and controlled release at specific sites. Liposomes, commonly used as drug carriers, constitute a fundamental part of these systems. Moreover, the drug–liposome model serves as a robust platform for investigating interaction processes at both cellular and molecular levels. To advance our understanding of drug carrier uptake mechanisms, we employed fluorescence lifetime imaging microscopy (FLIM) and fluorescence correlation spectroscopy (FCS), leveraging the unique benefits of two-photon (2P) excitation. Our approach utilized giant unilamellar vesicles (GUVs) as a simplified model system for cell membranes, labelled with the amphiphilic fluorescent dye 3,3′-dioctadecyloxa-carbocyanine (DiOC18(3)). Additionally, large unilamellar vesicles (LUVs) functioned as a drug carrier system, incorporating the spectrally distinct fluorescent sulforhodamine 101 (SRh101) as a surrogate drug. The investigation emphasized the diverse interactions between GUVs and LUVs based on the charged lipids employed. We examined the exchange kinetics and structural alterations of liposome carriers during the uptake process. Our study underscores the significance of employing 2P excitation in conjunction with FLIM and FCS. This powerful combination offers a valuable methodological approach for studying liposome interactions, positioning them as an exceptionally versatile model system with a distinct technical advantage.

Effect of Lipid Composition on the Interaction of Liposomes with THP-1-Derived Macrophages.

Recently, liposomal formulations that target macrophages have been used to treat lung diseases. However, the detailed mechanism of the cellular uptake must be elucidated to identify a formulation with excellent cellular uptake efficiency to treat non-tuberculous mycobacterial lung disease. We studied the effect of lipid composition on the cellular uptake of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/cholesterol (Chol) liposomes with a size of approximately 200 nm into THP-1-derived macrophages. The amount of DPPC/Chol liposomes (80/20 mol%) was greater than that of DPPC/Chol (60/40 mol%) and DPPC/Chol (67/33 mol%) liposomes. The anisotropy of 1,6-diphenyl-1,3,5-hexatriene indicated that the membrane fluidity of the DPPC/Chol (80/20 mol%) liposomes was higher than that of the other two liposomes. DPPC/Chol (80/20 mol%) and DPPC/Chol (67/33 mol%) liposomes were taken up via clathrin- and caveolae-mediated endocytosis and phagocytosis. However, proteins involved in cellular uptake through ligand-receptor interactions were adsorbed to a greater extent on DPPC/Chol (80/20 mol%) liposomes than on DPPC/Chol (67/33 mol%) liposomes. Pretreatment of cells with antibodies against the low-density lipoprotein receptor and scavenger receptor type B1 largely inhibited the uptake efficiency of DPPC/Chol (80/20 mol%) liposomes. Our results indicate that the membrane fluidity of DPPC/Chol liposomes, which is controlled by the Chol ratio, is an important factor in controlling protein adsorption and the subsequent uptake efficiency of liposomes.

Efficacy of a Maillard-type conjugate of whey protein isolate with chitosan as a carrier for a liposomal form of a combination of curcumin and balanced amounts of n-3 and n-6 PUFAs. Part II. Carrier behaviour under simulated in vitro digestion

The study evaluated the benefits of using the whey protein isolate (WPI)–chitosan (CHIT) carrier formed via a Maillard reaction step to enhance the bioavailability of a liposomal form of nutraceuticals during in vitro gastrointestinal digestion according to the INFOGEST protocol. Liposomes appeared uniformly released from their hydrolysed complex [WPI–CHIT]–(PC–FO–CUR) during both the gastric (54 ± 9%) and small intestinal (46 ± 7%) stages in vitro. This was due to the initial encapsulation of liposomes (94%) by both WPI and chitosan in the soluble fraction of the Maillard-type conjugate. During the gastric stage, the mucoadhesiveness of the complex was improved by covalently attaching chitosan to thermally denatured WPI. The WPI denaturation was confirmed by DSC. Furthermore, both components aided in maintaining the complex's mucoadhesiveness during the small intestinal stage. Laser light scattering, TEM, EPRS, and tensiometry characterized interactions of hydrolysed complex particles and liposomes with mucin or bile salts in the GIT in vitro.

Extracellular Vesicle and Lipoprotein Interactions.

Extracellular vesicles and lipoproteins are lipid-based biological nanoparticles that play important roles in (patho)physiology. Recent evidence suggests that extracellular vesicles and lipoproteins can interact to form functional complexes. Such complexes have been observed in biofluids from healthy human donors and in various in vitro disease models such as breast cancer and hepatitis C infection. Lipoprotein components can also form part of the biomolecular corona that surrounds extracellular vesicles and contributes to biological identity. Potential mechanisms and the functional relevance of extracellular vesicle-lipoprotein complexes remain poorly understood. This Review addresses the current knowledge of the extracellular vesicle-lipoprotein interface while drawing on pre-existing knowledge of liposome interactions with biological nanoparticles. There is an urgent need for further research on the lipoprotein-extracellular vesicle interface, which could return important mechanistic, therapeutic, and diagnostic findings.

Molecular Mechanisms of Cationic Fusogenic Liposome Interactions with Bacterial Envelopes.

Although fusogenic liposomes offer a promising approach for the delivery of antibiotic payloads across the cell envelope of Gram-negative bacteria, there is still a limited understanding of the individual nanocarrier interactions with the bacterial target. Using super-resolution microscopy, we characterize the interaction dynamics of positively charged fusogenic liposomes with Gram-negative (Escherichia coli) and Gram-positive (Bacillus subtilis) bacteria. The liposomes merge with the outer membrane (OM) of Gram-negative bacteria, while attachment or lipid internalization is observed in Gram-positive cells. Employing total internal reflection fluorescence microscopy, we demonstrated liposome fusion with model supported lipid bilayers. For whole E. coli cells, however, we observed heterogeneous membrane integrations, primarily involving liposome attachment and hemifusion events. With increasing lipopolysaccharide length, the likelihood of full-fusion events was reduced. The integration of artificial lipids into the OM of Gram-negative cells led to membrane destabilization, resulting in decreased bacterial vitality, membrane detachment, and improved codelivery of vancomycin─an effective antibiotic against Gram-positive cells. These findings provide significant insights into the interactions of individual nanocarriers with bacterial envelopes at the single-cell level, uncovering effects that would be missed in bulk measurements. This highlights the importance of conducting single-particle and single-cell investigations to assess the performance of next-generation drug delivery platforms.

Identification of a cryptic functional apolipophorin-III domain within the Prominin-1 gene of Litopenaeus vannamei

The Apolipophorin-III (apoLp-III) is reported as an essential protein element in lipids transport and incorporation in lepidopterans. Structurally, apoLp-III has an α-helix bundle structure composed of five α-helices. Interestingly, classic studies proposed a structural switch triggered by its interaction with lipids, where the α-helix bundle opens. Currently, the study of the apoLp-III has been limited to insects, with no homologs identified in other arthropods. By implementing a structure-based search with the Phyre2 algorithm surveying the shrimp Litopenaeus vannamei's transcriptome, we identified a putative apoLp-III in this farmed penaeid (LvApoLp-III). Unlike canonical apoLp-III, the LvApoLp-III was identified as an internal domain within the transmembrane protein Prominin-1. Structural modeling using the template-based Phyre2 and template-free AlphaFold algorithms rendered two distinct structural topologies: the α-helix bundle and a coiled-coil structure. Notably, the secondary structure composition on both models was alike, with differences in the orientation and distribution of the α-helices and hydrophobic moieties. Both models provide insights into the classical structural switch induced by lipids in apoLp-III. To corroborate structure/function inferences, we cloned the synthetic LvApoLp-III domain, overexpressed, and purified the recombinant protein. Circular dichroism measurements with the recombinant LvApoLp-III agreed with the structural models. In vitro liposome interaction demonstrated that the apoLp-III domain within the PROM1 of L.vannamei associated similarly to exchangeable apolipoproteins. Altogether, this work reports the presence of an apolipophorin-III domain in crustaceans for the first time and opens questions regarding its function and importance in lipid metabolism or the immune system.

Quality by design-assisted development of D-α-tocopherol polyethylene glycol 1000 succinate-incorporated gefitinib-loaded cationic liposome(s).

Aim: Gefitinib-loaded D-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-coated cationic liposomes (GEF-TPGS-LIPO+) were developed and optimized by the quality by design (QbD) approach for its potential anticancer effect. Methods/materials: Box-Behnken design (BBD) a systematic design of experiments was added to screen and optimize the formulation variables. Results: GEF-TPGS-LIPO+ shows vesicle size (210±4.82nm), polydispersity index(0.271±0.002), zeta potential (22.2±0.84mV) and entrapment efficiency (82.3±1.95). MTT result shows the enhanced cytotoxicity and higher intracellular drug uptake with highest and lowest levels of the reactive oxygen species and NF-κBexpressions on A549 lung cancer cells, determined by fluorescence-activated cell sortingflow cytometry. Conclusion: Potential anticancer effect on A549 cells might be found due to cationic liposomal interaction with cancer cells.

Liposomes - Human phagocytes interplay in whole blood: effect of liposome design

Nanomedicine holds immense potential for therapeutic manipulation of phagocytic immune cells. However, in vitro studies often fail to accurately translate to the complex in vivo environment. To address this gap, we employed an ex vivo human whole-blood assay to evaluate liposome interactions with immune cells. We systematically varied liposome size, PEG-surface densities and sphingomyelin and ganglioside content. We observed differential uptake patterns of the assessed liposomes by neutrophils and monocytes, emphasizing the importance of liposome design. Interestingly, our results aligned closely with published in vivo observations in mice and patients. Moreover, liposome exposure induced changes in cytokine release and cellular responses, highlighting the potential modulation of immune system. Our study highlights the utility of human whole-blood models in assessing nanoparticle-immune cell interactions and provides insights into liposome design for modulating immune responses.

Kartogenin-loaded liposomes coated with alkylated chondroitin sulfate for cartilage repair

Cartilage loss is a common clinical problem, which leads to significant pain, dysfunction, and even disability. As a result, there is growing interest in using small, non-protein molecules to protect or repair cartilage. Kartogenin (KGN), a small hydrophobic molecule, shows chondroprotective and chondrogenic properties. In this study, we embedded KGN in liposomes, and the whole system was stabilized by covering it with n-octadecylated (at two different substitution degrees) chondroitin sulfate (CS) derivatives. We investigated the interactions of empty liposomes and KGN-loaded liposomes with both CS derivatives using various physicochemical techniques, which revealed that hydrophobically modified CSs can interact with both neutral lipid membrane and negatively charged loaded-KGN lipid membrane. The cytotoxicity and chondrogenic properties of the polysaccharides and liposome-CS formulations of KGN were analyzed towards mesenchymal stem cells (MSCs). The results showed that the alkylated CS exhibited cytotoxic properties. The higher substituted CS self-assembles into stable nanoaggregates that can form a corona on the surface of liposomes, eliminating the overall cytotoxicity of this polymer. However, all tested chondrogenic markers' expression levels are enhanced for KGN-loaded liposomes and coated by lower substituted CS. Furthermore, the undesirable hypertrophy effect for this formulation significantly decreased compared to pure polymeric derivative.

Stability and cytotoxicity of biopolymer-coated liposomes for use in the oral cavity

This study investigates the stability and cytotoxicity of biopolymer-coated liposomes for use in the oral cavity. Liposomes (3 mM and 6 mM) were prepared by the thin film method and hydrated with phosphate buffer (PB) or glycerol phosphate buffer (G-PB). For coating, liposomes were added to a biopolymer solution of opposite charge. Particle stability was evaluated by measuring the size, polydispersity index, and zeta potential for up to 60 weeks. In vitro interaction of fluorescent-labelled biopolymer-coated liposomes and dysplastic oral keratinocytes was analyzed by confocal microscopy. Potential cytotoxicity was assessed in dysplastic oral keratinocytes by cell proliferation and cell viability. All three biopolymers showed good coating abilities for both concentrations and hydration media. The alginate coated liposomes in PB, 3 mM chitosan-coated liposomes in PB, and chitosan-coated liposomes in G-PB were stable for up to 60 weeks. In vitro studies demonstrated low cytotoxicity for all coated liposomes and non-specific cellular uptake of biopolymer-coated liposomes, independent of biopolymer, surface charge, lipid concentration and hydration media. All three formulations demonstrated low cytotoxicity and were considered safe. Alginate- and chitosan-coated liposomes demonstrated good stability over time and may be promising agents for use in the oral cavity and should be investigated further.

Antifungal liposomes: Lipid saturation and cholesterol concentration impact interaction withfungal and mammalian cells.

Liposomes are lipid-based nanoparticles that have been used to deliver encapsulated drugs for a variety of applications, including treatment of life-threatening fungal infections. By understanding the effect of composition on liposome interactions with both fungal and mammalian cells, new effective antifungal liposomes can be developed. In this study, we investigated the impact of lipid saturation and cholesterol content on fungal and mammalian cell interactions with liposomes. We used three phospholipids with different saturation levels (saturated hydrogenated soy phosphatidylcholine (HSPC), mono-unsaturated 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC), and di-unsaturated 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine (PLPC)) and cholesterol concentrations ranging from 15% to 40% (w/w) in our liposome formulations. Using flow cytometry, >80% of Candida albicans SC5314 cells were found to interact with all liposome formulations developed, while >50% of clinical isolates tested exhibited interaction with these liposomes. In contrast, POPC-containing formulations exhibited low levels of interaction with murine fibroblasts and human umbilical vein endothelial cells (<30%), while HSPC and PLPC formulations had >50% and >80% interaction, respectively. Further, PLPC formulations caused a significant decrease in mammalian cell viability. Formulations that resulted in low levels of mammalian cell interaction, minimal cytotoxicity, and high levels of fungal cell interaction were then used to encapsulate the antifungal drug, amphotericin B. These liposomes eradicated planktonic C. albicans at drug concentrations lower than free drug, potentially due to the high levels of liposome-C. albicans interaction. Overall, this study provides new insights into the design of liposome formulations towards the development of new antifungal therapeutics.

Complexes of Cationic Pyridylphenylene Dendrimers with Anionic Liposomes: The Role of Dendrimer Composition in Membrane Structural Changes.

In the last decades, dendrimers have received attention in biomedicine that requires detailed study on the mechanism of their interaction with cell membranes. In this article, we report on the role of dendrimer structure in their interaction with liposomes. Here, the interactions between cationic pyridylphenylene dendrimers of the first, second, and third generations with mixed or completely charged pyridyl periphery (D16+, D215+, D229+, and D350+) with cholesterol-containing (CL/Chol/DOPC) anionic liposomes were investigated by microelectrophoresis, dynamic light scattering, fluorescence spectroscopy, and conductometry. It was found that the architecture of the dendrimer, namely the generation, the amount of charged pyridynium groups, the hydrophobic phenylene units, and the rigidity of the spatial structure, determined the special features of the dendrimer-liposome interactions. The binding of D350+ and D229+ with almost fully charged peripheries to liposomes was due to electrostatic forces: the dendrimer molecules could be removed from the liposomal surfaces by NaCl addition. D350+ and D229+ did not display a disruptive effect toward membranes, did not penetrate into the hydrophobic lipid bilayer, and were able to migrate between liposomes. For D215+, a dendrimer with a mixed periphery, hydrophobic interactions of phenylene units with the hydrocarbon tails of lipids were observed, along with electrostatic complexation with liposomes. As a result, defects were formed in the bilayer, which led to irreversible interactions with lipid membranes wherein there was no migration of D215+ between liposomes. A first-generation dendrimer, D16+, which was characterized by small size, a high degree of hydrophobicity, and a rigid structure, when interacting with liposomes caused significant destruction of liposomal membranes. Evidently, this interaction was irreversible: the addition of salt did not lead to the dissociation of the complex.

Interaction of liposomes with bile salts investigated by asymmetric flow field-flow fractionation (AF4): A novel approach for stability assessment of oral drug carriers

For oral drug delivery the stability of liposomes against intestinal bile salts is of key importance. Here, asymmetric flow field-flow fractionation (AF4) coupled to multi-angle laser light scattering (MALLS) and a differential refractive index (dRI) detector was employed to monitor structural re-arrangement of liposomes upon exposure to the model bile salt taurocholate. For comparison, a conventional stability assay was employed using a hydrophilic marker and size exclusion chromatography (SEC) to separate released from liposome-entrapped dye.Calcein-containing liposomes with and without cholesterol were compared in terms of their in vitro stability upon exposure to bile salts by separating liposomes from co-existing colloidal species emerging after stress test using AF4/MALLS/dRI. Dynamic light scattering (DLS) was utilized in parallel.Our AF4/MALLS/dRI results suggested that exposure of egg-phospholipid liposomes to bile salts at physiological concentrations led to the formation of two new species of colloidal associates, likely (mixed) micelles. Subjecting cholesterol-containing liposomes to the same bile media did not lead to any new colloidal structures, indicating increased stability of these liposomes. Our SEC-based release assay largely confirmed these findings, indicating that AF4/MALLS/dRI is a suitable technique for prediction of in vitro oral stability of liposomal formulations. Moreover, the powerful AF4/MALLS/dRI technique appears promising to improve the understanding of the underlying mechanisms during bile salt-induced liposomal breakdown.

Exploring the Usability of α-MSH-SM-Liposome as an Imaging Agent to Study Biodegradable Bone Implants In Vivo.

Novel biodegradable metal alloys are increasingly used as implant materials. The implantation can be accompanied by an inflammatory response to a foreign object. For studying inflammation in the implantation area, non-invasive imaging methods are needed. In vivo imaging for the implanted area and its surroundings will provide beneficiary information to understand implant-related inflammation and help to monitor it. Therefore, inflammation-sensitive fluorescent liposomes in rats were tested in the presence of an implant to evaluate their usability in studying inflammation. The sphingomyelin-containing liposomes carrying alpha-melanocyte-stimulating hormone (α-MSH)-peptide were tested in a rat bone implant model. The liposome interaction with implant material (Mg-10Gd) was analyzed with Mg-based implant material (Mg-10Gd) in vitro. The liposome uptake process was studied in the bone-marrow-derived macrophages in vitro. Finally, this liposomal tracer was tested in vivo. It was found that α-MSH coupled sphingomyelin-containing liposomes and the Mg-10Gd implant did not have any disturbing influence on each other. The clearance of liposomes was observed in the presence of an inert and biodegradable implant. The degradable Mg-10Gd was used as an alloy example; however, the presented imaging system offers a new possible use of α-MSH-SM-liposomes as tools for investigating implant responses.

SPRi analysis of molecular interactions of mApoE-functionalized liposomes as drug delivery systems for brain diseases.

The application of liposomes (LPs) to central nervous system disorders could represents a turning point in the therapy and quality of life of patients. Indeed, LPs have demonstrated their ability to cross the blood-brain barrier (BBB) and, as a consequence, to enhance the therapeutics delivery into the brain. Some approaches for BBB crossing involve the modification of LP surfaces with biologically active ligands. Among them, the Apolipoprotein E-modified peptide (mApoE) has been used for several LP-based nanovectors under investigation. In this study, we propose Surface Plasmon Resonance imaging (SPRi) for the characterization of multifunctionalized LPs for Glioblastoma treatment. LPs were functionalized with mApoE and with a metallo-protease sensitive lipopeptide to deliver and guarantee the localized release of an encapsulated drug in diseased areas. The SPRi analysis was optimized in order to evaluate the binding affinity between LPs and mApoE receptors, finding that mApoE-LPs generated SPRi signals referred to interactions between mApoE and receptors mainly present in the brain. Moreover, a significant binding between LPs and VCAM-1 (endothelial receptor) was observed, whereas LPs did not interact significantly with peripheral receptors expressed on monocytes and lymphocytes. SPRi results confirmed not only the presence of mApoE on LP surfaces, but also its binding affinity, thanks to the specific interaction with selected receptors. In conclusion, the high sensitivity and the multiplexing capability associated with the low volumes of sample required and the minimal sample preparation, make SPRi an excellent technique for the characterization of multifunctionalized nanoparticles-based formulations.

Self-assembled hyaluronic acid-coated nanocomplexes for targeted delivery of curcumin alleviate acute kidney injury

Acute kidney injury (AKI) is a pathological process with high morbidity, and drug resistance is easy to occur due to untargeted drug therapy. Curcumin can repair acute kidney injury. The expression of the CD44 receptor in renal tubular epithelial cells is abnormally elevated during AKI, and hyaluronic acid (HA) has the ability to bind specifically to the CD44 receptor. In this study, we developed a hyaluronic acid-coated liposome (HALP) nanocomplexes that targeted renal epithelial cells and its effect of relieving AKI was investigated. HALP was formed by self-assembly through the electrostatic interaction of curcumin-loaded cationic liposomes (LP) with hyaluronic acid and responds to the release of curcumin in the acidic microenvironment of lesions to treat AKI. HALP had good stability and biocompatibility. The in vitro results showed that compared to LP, HALP exhibited higher antioxidant, anti-inflammatory, and anti-apoptotic capacities. The AKI model suggested that HALP could not only target and accumulate in the injured kidney but also had an excellent ability to reduce the inflammatory response, which decreased tubular necrosis and restored kidney function.