Liposomal Nanocarriers Research Articles

Liposome Nanocarriers Based on γ Oryzanol: Preparation, Characterization, and In Vivo Assessment of Toxicity and Antioxidant Activity.

The present study aimed to develop and characterize liposome nanocarriers based on γ oryzanol and evaluate their potential in vitro and in vivo toxicity and antioxidant effects. The liposomes were physicochemically characterized using various techniques, including dynamic light scattering (DLS) for size and polydispersity index (PDI) measurements and ζ-potential analysis. The in vitro toxicity assessments were performed using hemolysis and MTT assays on the HS5 cell line. In vivo, acute oral toxicity was evaluated by using LD50 assays in mice. Additionally, antioxidant activity was assessed through biochemical analysis of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and liver tissue catalase, malondialdehyde (MDA), and glutathione (GSH) levels. The results revealed that the liposomes exhibited a uniform and spherical morphology with suitable physicochemical properties for drug delivery applications. The in vitro cytotoxicity and hemolysis assays and the in vivo LD50 experiment indicated the potential safety of γ oryzanol liposomes, especially at lower concentrations. In addition, the assessment of liver enzymes, i.e., ALT and AST, and the antioxidant markers further revealed the safety of the formulation, particularly for the liver as a highly sensitive soft organ. Overall, the liposome nanocarriers based on γ oryzanol were successfully formulated and expressed potential safety, supporting their application for the purposes of drug delivery and therapeutic interventions, particularly for hepatocellular and antioxidant therapies; however, further investigations for preclinical and clinical studies could be the future prospects for liposome nanocarriers based on γ oryzanol to explore the safety and efficacy of these nanocarriers in various disease models and clinical settings.

Nanotechnological synergy of mangiferin and curcumin in modulating PI3K/Akt/mTOR pathway: a novel front in ovarian cancer precision therapeutics.

Background: Ovarian cancer, colloquially termed the "silent killer" among gynecological malignancies, remains elusive due to its often-asymptomatic progression and diagnostic challenges. Central to its pathogenesis is the overactive PI3K/Akt/mTOR signaling pathway, responsible for various cellular functions, from proliferation to survival. Within this context, the phytochemical compounds mangiferin (derived from Mangifera indica) and curcumin (from Curcuma longa) stand out for their potential modulatory effects. However, their inherent bioavailability challenges necessitate innovative delivery systems to maximize therapeutic benefits. Objective: This study seeks to synergize the merits of nanotechnology with the therapeutic properties of mangiferin and curcumin, aiming to bolster their efficacy against ovarian cancer. Methods: Employing specific nanotechnological principles, we engineered exosomal and liposomal nano-carriers for mangiferin and curcumin, targeting the PI3K/Akt/mTOR pathway. Molecular docking techniques mapped the interactions of these phytochemicals with key proteins in the pathway, analyzing their binding efficiencies. Furthermore, molecular dynamics simulations, spanning 100 nanoseconds, verified these interactions, with additional computational methodologies further validating our findings. The rationale for the 100 nanoseconds time span lies in its sufficiency to observe meaningful protein-ligand interactions and conformational changes. Notably, liposomal technology provided an enhancement in drug delivery by protecting these compounds from degradation, allowing controlled release, and improving cellular uptake. Results: Our computational investigations demonstrated notable binding affinities of mangiferin and curcumin: PI3K at -11.20kcal/mol, Akt at -15.16kcal/mol, and mTOR at -10.24kcal/mol. The adoption of exosome/liposome-mediated delivery significantly amplified the bioavailability and cellular uptake of these nano-formulated compounds, positioning them as potential stalwarts in ovarian cancer intervention. A brief explanation of exosome/liposome-mediated delivery involves the use of these vesicles to encapsulate and transport therapeutic agents directly to the target cells, enhancing drug delivery efficiency and minimizing side effects. Conclusion: Addressing ovarian cancer's intricacies, dominated by the erratic PI3K/Akt/mTOR signaling, mandates innovative therapeutic strategies. Our pioneering approach converges nanotechnological liposomal delivery with mangiferin and curcumin's natural efficacies. This confluence, validated by computational insights, heralds a paradigm shift in ovarian cancer treatment. As our findings underscore the collaborative potential of these phytochemicals, it beckons further exploration in translational studies and clinical applications, ensuring the best intersection of nature and technology for therapeutic advantage.

Near-infrared activated liposomes for neuroprotection in glaucoma.

Neurodegenerative diseases have a profound impact on vision, leading to conditions such as glaucoma, optic neuropathy, and diabetic retinopathy, affecting millions worldwide. These diseases are characterized by the degeneration of retinal ganglion cells (RGCs), resulting in a progressive loss of visual acuity and field, with the threat of irreversible blindness. However, existing treatments, such as eye drops, direct injections, and laser surgeries face significant challenges due to limited efficacy and potential infection. The inefficiency of traditional corneal drug delivery methods is a major obstacle in treating vision neurodegenerative diseases. To address these challenges, we developed a remotely triggered on-demand liposomal delivery system to treat glaucomatous neurodegeneration in mice. We utilized the localized surface plasmon resonance (LSPR) effect of gold nanorods (AuNRs) under near-infrared (NIR) light (808 nm) to control the release of cyclodextrin-encapsulated melatonin from thermally responsive liposomal nanocarriers in the vitreous humor. Due to the transparency of the eye's cornea, NIR light can penetrate deep tissues, enabling on-demand drug delivery to the retina. By enhancing the drug's solubility and stability through cyclodextrin encapsulation, this remotely activated melatonin/HPβCD AuNRs liposomes delivery system can decrease intraocular pressure (IOP) elevation by (24 ± 7)%, enhance the survival rate of RGCs by (77 ± 6)%, and decrease glial fibrillary acidic protein (GFAP) activation by (75 ± 6)% at depth in an acute experimental glaucoma model. This NIR-triggered drug delivery system presents the potential of a promising minimally photo-triggered therapeutic option for glaucoma treatment.

Indocyanine Green-Loaded Liposomes-Assisted Photoacoustic Computed Tomography for Evaluating In Vivo Tumor Penetration of Liposomal Nanocarriers.

Liposomes possess the potential to enhance drug solubility, prolong the duration of circulation, and augment drug accumulation at the tumor site through passive and active targeting strategies. However, there is a lack of studies examining the in vivo tumor penetration capabilities of liposomes of varying sizes, which hampers the development of drug delivery systems utilizing liposomal nanocarriers. Here, we present an indocyanine green (ICG)-loaded liposomes-assisted photoacoustic computed tomography (PACT) for directly evaluating the tumor penetration ability of liposomal nanocarriers in vivo. Through the utilization of microfluidic mixing combined with extrusion techniques, we successfully prepare liposomes encapsulating ICG in both large (192.6 ± 8.0 nm) and small (61.9 ± 0.6 nm) sizes. Subsequently, we designed a dual-wavelength PACT system to directly monitor the in vivo tumor penetration of large- and small-size ICG-encapsulated liposomes. In vivo PACT experiments indicate that ICG-loaded liposomes of smaller size exhibit enhanced penetration capability within tumor tissues. Our work presents a valuable approach to directly assess the penetration ability of liposomal nanocarriers in vivo, thereby facilitating the advancement of drug delivery systems with enhanced tumor penetration and therapeutic efficacy.

Improved pharmacokinetics and enhanced efficacy of the vancomycin derivative FU002 using a liposomal nanocarrier

Antibiotic resistance still represents a global health concern which diminishes the pool of effective antibiotics. With the vancomycin derivative FU002, we recently reported a highly potent substance active against Gram-positive bacteria with the potential to overcome vancomycin resistance. However, the translation of its excellent antimicrobial activity into clinical efficiency could be hampered by its rapid elimination from the blood stream. To improve its pharmacokinetics, we encapsulated FU002 in PEGylated liposomes. For PEG-liposomal FU002, no relevant cytotoxicity on liver, kidney and red blood cells was observed. Studies in Wistar rats revealed a significantly prolonged blood circulation of the liposomal antibiotic. In microdilution assays it could be demonstrated that encapsulation does not diminish the antimicrobial activity against staphylococci and enterococci. Highlighting its great potency, liposomal FU002 exhibited a superior therapeutic efficacy when compared to the free form in a Galleria mellonella larvae infection model.

Enhanced Anti‐Photoaging Effects of Adipose‐Derived Stem Cell (ADSC) Secretome via Liposomal and Iontophoretic Intradermal Delivery

AbstractThe growing societal concern regarding skin aging caused by ultraviolet (UV) exposure has spurred the quest for effective therapeutic solutions. Among these, secreted factors derived from adipose‐derived stem cells (ADSC) have emerged as promising candidates with anti‐photoaging properties. The secretome of ADSC stimulates resident fibroblasts, triggering antioxidant effects and promoting the synthesis of the extracellular matrix, thus counteracting the effects of photoaging. In this study, the potential of dried ADSC secretome (AD‐Sc), obtained through a compressed fluid antisolvent process, is assessed as an anti‐photoaging agent. In addition, liposome nanocarriers are used to encapsulate AD‐Sc (Sc_Lipo) to enhance its delivery efficiency. The findings demonstrate that both AD‐Sc and Sc_Lipo effectively reduce reactive oxygen species levels in UV‐damaged human fibroblasts, upregulate the expression of HAS1 and COL1, and inhibit MMP2. Moreover, it is discovered that reverse electrodialysis (RED)‐driven iontophoresis improves the intradermal delivery of Sc_Lipo, as validated in an ex vivo porcine skin. Finally, in an in vivo UV‐induced wrinkling mice model, the Lipo+RED group shows noticeable skin photoaging improvements. This study provides additional evidence that a combined intradermal delivery system for AD‐Sc may represent a viable therapeutic approach for mitigating and preventing photoaging in clinical settings.

CCL2 chemokine inhibition primes the tumor vasculature for improved nanomedicine delivery and efficacy

Blood vessel functionality is crucial for efficient tumor-targeted drug delivery. Heterogeneous distribution and perfusion of angiogenic blood vessels contribute to suboptimal accumulation of (nano-) therapeutics in tumors and metastases. To attenuate pathological angiogenesis, an L-RNA aptamer inhibiting the CC motif chemokine ligand 2 (CCL2) was administered to mice bearing orthotopic 4T1 triple-negative breast cancer tumors. The effect of CCL2 inhibition on tumor blood vessel functionality and tumor-targeted drug delivery was evaluated via multimodal and multiscale optical imaging, employing fluorophore-labeled polymeric (10 nm) and liposomal (100 nm) nanocarriers. Anti-CCL2 treatment induced a dose-dependent anti-angiogenic effect, reflected by a decreased relative blood volume, increased blood vessel maturity and functionality, and reduced macrophage infiltration, accompanied by a shift in the polarization of tumor-associated macrophages (TAM) towards a less M2-like and more M1-like phenotype. In line with this, CCL2 inhibitor treatment improved the delivery of polymers and liposomes to tumors, and enhanced the antitumor efficacy of free and liposomal doxorubicin. Together, these findings demonstrate that blocking the CCL2-CCR2 axis modulates TAM infiltration and polarization, resulting in vascular normalization and improved tumor-targeted drug delivery.

Enhancement of the bioavailability of phenolic compounds from fruit and vegetable waste by liposomal nanocarriers.

Fruits and vegetables are one of the most consumed and processed commodities globally and comprise abundant phenolic compounds, one of the main nutraceuticals in the food industry. Comparably elevated rates of these compounds are found in waste (peel, seeds, leaf, stem, etc.) in the food processing industry. They are being investigated for their potential use in functional foods. However, phenolic compounds' low bioavailability limits their application, which can be approached by loading the phenolic compounds into an encapsulation system such as liposomal carriers. This review aims to elucidate the recent trend in extracting phenolic compounds from the waste stream and the means to load them in stable liposomes. Furthermore, the application of these liposomes with only natural extracts in food matrices is also presented. Many studies have indicated that liposomes can be a proper candidate for encapsulating and delivering phenolic compounds and as a means to increase their bioavailability.

Integrating Reliable Pt-S Bond-Mediated 3D DNA Nanomachine with Magnetic Separation in a Homogeneous Electrochemical Strategy for Exosomal MicroRNA Detection with Low Background and High Sensitivity.

Precise and sensitive analysis of exosomal microRNA (miRNA) is of great importance for noninvasive early disease diagnosis, but it remains a great challenge to detect exosomal miRNA in human blood samples because of their small size, high sequence homology, and low abundance. Herein, we integrated reliable Pt-S bond-mediated three-dimensional (3D) DNA nanomachine and magnetic separation in a homogeneous electrochemical strategy for the detection of exosomal miRNA with low background and high sensitivity. The 3D DNA nanomachine was easily prepared via a facile and rapid freezing method, and it was capable of resisting the influence of biothiols, thus endowing it with high stability. Notably, the as-developed magnetic 3D DNA nanomachine not only enabled the detection system to have a low background but also coupled with liposome nanocarriers to synergistically amplify the current signal. Consequently, by ingeniously combining the low background and multiple signal-amplification strategies in homogeneous electrochemical biosensing, highly sensitive detection of exosomal miRNA was successfully achieved. More significantly, with good anti-interference ability, the as-proposed method could effectively discriminate plasma samples from cancer patients and healthy subjects, thus showing a high potential for application in the nondestructive early clinical diagnosis of disease.

Ameliorative anticancer effect of dendrimeric peptide modified liposomes of letrozole: In vitro and in vivo performance evaluations

Letrozole (LTZ) loaded dendrimeric nano-liposomes were prepared for targeted delivery to breast cancer cells. Surface modification with cationic peptide dendrimers (PDs) and a cancer specific ligand, transferrin (Tf), was attempted. Arginine-terminated PD (D-1) and Arginine-terminated, lipidated PD (D-2) were synthesized using Solid Phase Peptide Synthesis, purified by preparative HPLC and characterized using 1HNMR, MS and DSC analyses. Surface modification of drug loaded liposomes with Tf and/or PD was carried out. Formulations were characterized using FTIR, DSC, 1HNMR, XRD and TEM. Tf-conjugated LTZ liposomes (LTf) and Tf/D-2-conjugated LTZ liposomes (LTfD-2) showed greater cytotoxic potential (IC50 = 95.03 µg/mL and 23.75 µg/mL respectively) with enhanced cellular uptake in MCF7 cells compared to plain LTZ. Blocking studies of Tf (Tf-receptor mediated internalization) revealed decreased uptake of LTf and LTfD-2 confirming the role of Tf in uptake of Tf-conjugated liposomes. Intravenous treatment with LTfD-2 caused highest reduction in tumor volumes of female BALB/c-nude mice (145 mm3) compared to plain LTZ (605 mm3) and unconjugated LTZ liposomes (LP) (300 mm3). In vivo biodistribution studies revealed higher fluorescence in tumor tissue and liver of LTfD-2 treated mice than LTf or LP treatment. Immunohistochemical studies revealed greater apoptotic potential of LTfD-2 as indicated by TUNEL assay and ROS detection assay. The study reveals the superior therapeutic efficacy of the developed LTZ liposomal nanocarriers using PDs to enhance the transfection efficiency in addition to modifying the surface characteristics by attaching a targeting ligand for active drug targeting to breast cancer cells.

Liposomal nanocarriers containing siRNA as small molecule-based drugs to overcome cancer drug resistance.

This review discusses the application of nanoliposomes containing siRNA/drug to overcome multidrug resistancefor all types of cancer treatments. As drug resistance-associated factors are overexpressed in many cancer cell types, pumping chemotherapy drugs out of the cytoplasm leads to an inadequate therapeutic response. The siRNA/drug-loaded nanoliposomes are a promising approach to treating multidrug-resistantcancer, as they can effectively transmit a small-molecule drug into the target cytoplasm, ensuring that the drug binds efficiently. Moreover, nanoliposome-based therapeutics with advances in nanotechnology can effectively deliver siRNA to cancer cells. Overall, nanoliposomes have the potential to effectively deliver siRNA and small-molecule drugs in a targeted manner and are thus a promising tool for the treatment of cancer and other diseases.

Drug delivery by sonosensitive liposome and microbubble with acoustic-lens attached ultrasound: an in vivo feasibility study in a murine melanoma model

Conventional chemotherapy methods have adverse off-target effects and low therapeutic efficiencies of drug release in target tumors. In this study, we proposed a combination therapy of doxorubicin (DOX)-loaded ultrasound (US)-sensitive liposomal nanocarriers (IMP301), microbubbles (MBs) under focused US exposure using convex acoustic lens-attached US (LENS) to tumor treatment. The therapeutic effects of each treatment in a murine melanoma model were evaluated using contrast-enhanced US (CEUS) and micro-computed tomography (micro-CT) imaging, bioluminescence and confocal microscopy imaging, and liquid chromatography–mass spectroscopy (LC/MS) analysis. Tumor-bearing mice were randomly assigned to one of the following groups: (1) G1: IMP301 only (n = 9); (2) G2: IMP301 + LENS (n = 9); (3) G3: IMP301 + MB + LENS (n = 9); (4) G4: DOXIL only (n = 9); and (5) G5: IMP301 without DOXIL group as a control group (n = 4). Ten days after tumor injection, tumor-bearing mice were treated according to each treatment strategy on 10th, 12th, and 14th days from the day of tumor injection. The CEUS images of the tumors in the murine melanoma model clearly showed increased echo signal intensity from MBs as resonant US scattering. The relative tumor volume of the G2 and G3 groups on the micro-CT imaging showed inhibited tumor growth than the reference baseline of the G5 group. DOX signals on bioluminescence and confocal microscopy imaging were mainly located at the tumor sites. LC/MS showed prominently higher intratumoral DOX concentration in the G3 group than in other treated groups. Therefore, this study effectively demonstrates the feasibility of the synergistic combination of IMP301, MBs, and LENS-application for tumor-targeted treatment. Thus, this study can enable efficient tumor-targeted treatment by combining therapy such as IMP301 + MBs + LENS-application.

Smart Liposomal Nanocarrier Enhanced the Treatment of Ischemic Stroke through Neutrophil Extracellular Traps and Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase-Stimulator of Interferon Genes (cGAS-STING) Pathway Inhibition of Ischemic Penumbra.

Brain inflammation is regarded as one of the leading causes that aggravates secondary brain injury and hinders the prognosis of ischemic stroke. After ischemic stroke, high quantities of peripheral neutrophils are recruited to brain lesions and release neutrophil extracellular traps (NETs), leading to the aggravation of blood-brain barrier (BBB) damage, activation of microglia, and ultimate neuronal death. Herein, a smart multifunctional delivery system has been developed to regulate immune disorders in the ischemic brain. Briefly, Cl-amidine, an inhibitor of peptidylarginine deiminase 4 (PAD4), is encapsulated into self-assembled liposomal nanocarriers (C-Lipo/CA) that are modified by reactive oxygen species (ROS)-responsive polymers and fibrin-binding peptide to achieve targeting ischemic lesions and stimuli-responsive release of a drug. In the mouse model of cerebral artery occlusion/reperfusion (MCAO), C-Lipo/CA can suppress the NETs release process (NETosis) and further inhibit the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway in an ischemic brain. In addition, MCAO mice treated with C-Lipo/CA significantly mitigated ischemic and reperfusion injury, with a reduction in the area of cerebral infarction to 12.1%, compared with the saline group of about 46.7%. These results demonstrated that C-Lipo/CA, which integrated microglia regulation, BBB protection, and neuron survival, exerts a potential therapy strategy to maximize ameliorating the mortality of ischemic stroke.

Constitutively Synergistic Multiagent Drug Formulations Targeting MERTK, FLT3, and BCL-2 for Treatment of AML.

Although high-dose, multiagent chemotherapy has improved leukemia survival rates, treatment outcomes remain poor in high-risk subsets, including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in infants. The development of new, more effective therapies for these patients is therefore an urgent, unmet clinical need. The dual MERTK/FLT3 inhibitor MRX-2843 and BCL-2 family protein inhibitors were screened in high-throughput against a panel of AML and MLL-rearranged precursor B-cell ALL (infant ALL) cell lines. A neural network model was built to correlate ratiometric drug synergy and target gene expression. Drugs were loaded into liposomal nanocarriers to assess primary AML cell responses. MRX-2843 synergized with venetoclax to reduce AML cell density in vitro. A neural network classifier based on drug exposure and target gene expression predicted drug synergy and growth inhibition in AML with high accuracy. Combination monovalent liposomal drug formulations delivered defined drug ratios intracellularly and recapitulated synergistic drug activity. The magnitude and frequency of synergistic responses were both maintained and improved following drug formulation in a genotypically diverse set of primary AML bone marrow specimens. We developed a nanoscale combination drug formulation that exploits ectopic expression of MERTK tyrosine kinase and dependency on BCL-2 family proteins for leukemia cell survival in pediatric AML and infant ALL cells. We demonstrate ratiometric drug delivery and synergistic cell killing in AML, a result achieved by a systematic, generalizable approach of combination drug screening and nanoscale formulation that may be extended to other drug pairs or diseases in the future.

MicroRNA delivery based on nanoparticles of cardiovascular diseases.

Cardiovascular disease, especially myocardial infarction, is a serious threat to human health. Many drugs currently used cannot achieve the desired therapeutic effect due to the lack of selectivity. With the in-depth understanding of the role of microRNA (miRNA) in cardiovascular disease and the wide application of nanotechnology, loading drugs into nanoparticles with the help of nano-delivery system may have a better effect in the treatment of cardiomyopathy. In this review, we highlight the latest research on miRNAs in the treatment of cardiovascular disease in recent years and discuss the possibilities and challenges of using miRNA to treat cardiomyopathy. Secondly, we discuss the delivery of miRNA through different nano-carriers, especially inorganic, polymer and liposome nano-carriers. The preparation of miRNA nano-drugs by encapsulating miRNA in these nano-materials will provide a new treatment option. In addition, the research status of miRNA in the treatment of cardiomyopathy based on nano-carriers is summarized. The use of this delivery tool cannot only realize therapeutic potential, but also greatly improve drug targeting and reduce side effects.

Preparation, Characterization and Cytotoxic Studies of Cisplatin-containing Nanoliposomes on Breast Cancer Cell Lines

Objective: Today, cancer is one the most important challenges in modern medicine. Breast carcinoma is one type of cancer that is treated with cisplatin, a chemotherapy drug. By using liposomal nanocarriers, this study seeks to increase the therapeutic efficiency of cisplatin. Method: The zeta potential, particle size, and drug-release characteristics of nanoliposomal cisplatin were evaluated after it had been synthesized using the reverse phase evaporation technique. The cytotoxicity rate of nanoliposomal cisplatin was then assessed using the T-47D breast cancer cell line. Results: This study’s liposomal nanoparticles (NPs) had a zeta potential of -24.9 mV and a particle size of 342.3 nm. 3.51% and 79.6%, respectively, were found to be the drug loading level and amount of encapsulated drug. A significant improvement over the free drug was seen in this nanoliposome’s cytotoxic effect on the T-47D breast cancer cell line (P<0.05). Conclusion: According to what we have discovered, cisplatin liposomal nanocarriers may prove to be a cutting-edge chemotherapy treatment for breast cancer.

Liposomal nanocarriers of preassembled glycocalyx expeditiously restore endothelial glycocalyx in endotoxemia.

The endothelial glycocalyx (EG) is degraded early during sepsis, and currently available treatments are not effective in promptly restoring it. Here, we created liposomal nanocarriers of preassembled glycocalyx (LNPG) by synthesizing glycosylated syndecan-1 and inserting it into the lipid membrane of unilamellar liposomes. We hypothesized that LNPG would fuse with the endothelial cells where EG is degraded and restore EG in sepsis. We induced endotoxemia in C57BL/6J mice using lipopolysaccharides (LPS) and treated them with LNPG, saline, syndecan-1, or liposomes. LNPG significantly prolonged the survival time of LPS-treated mice compared with the other treatments. Immunostaining of en face mesenteric arteries of LPS-treated mice showed that syndecan-1 was fully restored after LNPG administration. In addition, EG height in microvasculature of mouse cremaster muscle was monitored using sidestream dark field imaging. LNPG restored the perfused boundary region (PBR), which is inversely related to EG dimensions, to the control level after LPS administration. Furthermore, flow-induced dilation in isolated mouse mesenteric arterioles was fully recovered after LNPG treatment in LPS-treated mice. In summary, our findings provide evidence of the therapeutic efficacy of LNPG in the LPS-induced mouse model of sepsis, achieved by expeditiously restoring EG through fusion of LNPG with the endothelial plasma membrane and recovery of endothelial function.NEW & NOTEWORTHY Vascular endothelial cells represent the first line of exposure to bacterial endotoxins. Here, we propose a novel therapeutic strategy using liposomes to deliver preassembled glycocalyx to vascular endothelial cell surface and consequently restore endothelial glycocalyx (EG). We tested liposomal nanocarriers of preassembled glycocalyx (LNPG) in vivo and ex vivo to establish for the first time their expeditious therapeutic efficacy in improving survival of lipopolysaccharides (LPS)-treated mice, as achieved by the restoration of EG and recovery of endothelial function.

Linalool-Incorporated Synergistically Engineered Modified Liposomal Nanocarriers for Enhanced Transungual Delivery of Terbinafine against Onychomycosis.

This work investigates the synthesis of linalool-containing invasomes for terbinafine (TBF-IN) in order to increase the solubility, bioavailability, and nail permeability of terbinafine (TBF) for transungual administration. TBF-IN was created utilising the thin-film hydration technique, and with the Box-Behnken design (BBD), optimisation was carried out. TBF-INopt were investigated for vesicle size, zeta potential, PDI (Polydispersity index), entrapment efficiency (EE) and in vitro TBF release. In addition, nail permeation analysis, TEM (transmission electron microscopy), and CLSM (confocal scanning laser microscopy) were performed for further evaluation. The TBF-INopt exhibited spherical as well as sealed vesicles with a considerably small size of 146.3 nm, an EE of 74.23 per cent, a PDI of 0.1612, and an in vitro release of 85.32 per cent. The CLSM investigation revealed that the new formulation had better TBF nail penetration than the TBF suspension gel. The antifungal investigation demonstrated that the TBF-IN gel has superior antifungal activity against Trichophyton rubrum and Candida albicans compared to the commercially available terbinafine gel. In addition, an investigation of skin irritation using Wistar albino rats indicates that the TBF-IN formulation is safe for topical treatment. This study confirmed that the invasomal vesicle formulation is an effective vehicle for the transungual delivery of TBF for the treatment of onychomycosis.

An Inhalable Hybrid Biomimetic Nanoplatform for Sequential Drug Release and Remodeling Lung Immune Homeostasis in Acute Lung Injury Treatment.

Interactions of lung macrophages and recruited neutrophils with the lung microenvironment continuously aggravate the dysregulation of lung inflammation in the pathogenesis of acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Either modulating macrophages or destroying neutrophil counts cannot guarantee a satisfactory outcome in ARDS treatment. Aimed at inhibiting the coordinated action of neutrophils and macrophages and modulating the hyper-inflammatory condition, an inhalable biomimetic sequential drug-releasing nanoplatform was developed for the combinatorial treatment of ALI. The nanoplatform (termed D-SEL) was made by conjugating DNase I, as outer cleavable arms, to a serum exosomal and liposomal hybrid nanocarrier (termed SEL) via a matrix metalloproteinase 9 (MMP-9)-cleavable peptide and then encapsulating methylprednisolone sodium succinate (MPS). In lipopolysaccharide (LPS) induced ALI in mice, the MPS/D-SEL moved through muco-obstructive airways and was retained in the alveoli for over 24 h postinhalation. DNase I was then released from the nanocarrier first after responding to MMP-9, resulting in inner SEL core exposure, which precisely delivered MPS into macrophages for promoting M2 macrophage polarization. Local and sustained DNase I release degraded dysregulated neutrophil extracellular traps (NETs) and suppressed neutrophil activation and the mucus plugging microenvironment, which in turn amplified M2 macrophage polarization efficiency. Such dual-stage drug release behavior facilitated down-regulation of pro-inflammatory cytokines in the lung but anti-inflammatory cytokine production through remodeling lung immune homeostasis, ultimately promoting lung tissue repair. This work presents a versatile hybrid biomimetic nanoplatform for the local pulmonary delivery of dual-drug therapeutics and displays potential in the treatment of acute inflammation.

Optimization of solvent evaporation method in liposomal nanocarriers loaded-garlic essential oil (Allium sativum): Based on the encapsulation efficiency, antioxidant capacity, and instability.

This study is aimed to optimise the preparation factors, such as sonication time (5-20min), cholesterol to lecetin ratio (CHLR) (0.2-0.8), and essential oil content (0.1-0.3g/100g) in solvent evaporation method for formulation of liposomal nanocarriers containing garlic essential oil (GEO) in order to find the highest encapsulation efficiency and stability with strongest antioxidant and antimicrobial activity. The droplet size, zeta potential, encapsulation efficiency, turbidity, changes in turbidity after storage (as a measure of instability), antioxidant capacity, and antimicrobial activity were measured for all prepared samples of nanoliposome. The sonication time is recognised as the most effective factor on the droplet size, zeta potential, encapsulation efficiency, turbidity, and instability while CHLR was the most effective factor on zeta potential and instability. The content of GEO significantly affected the antioxidant and antimicrobial activity in particular against gram-negative bacteria (Escherichia coli). The results of FTIR based on the identification of functional groups confirmed the presence of GEO in the spectra of the prepared nanoliposome and also it was not observed the interaction between the components of the nanoliposome. The overall optimum conditions were determined by response surface methodology (RSM) as the predicted values of the studied factors (sonication time: 18.99min, CHLR: 0.59 and content of GEO: 0.3g/100g) based on obtaining the highest stability and efficiency as well as strongest antioxidant and antimicrobial activity.