"All in one" lipid-polymer nanodelivery system for gene therapy of ischemic diseases.

Gene therapy offers a promising avenue for treating ischemic diseases, yet its clinical efficacy is hindered by the limitations of single gene therapy and the high oxidative stress microenvironment characteristic of such conditions. Lipid-polymer hybrid vectors represent a novel approach to enhance the effectiveness of gene therapy by harnessing the combined advantages of lipids and polymers. In this study, we engineered lipid-polymer hybrid nanocarriers with tailored structural modifications to create a versatile membrane fusion lipid-nuclear targeted polymer nanodelivery system (FLNPs) optimized for gene delivery. Our results demonstrate that FLNPs facilitate efficient cellular uptake and gene transfection via membrane fusion, lysosome avoidance, and nuclear targeting mechanisms. Upon encapsulating Hepatocyte Growth Factor plasmid (pHGF) and Catalase plasmid (pCAT), HGF/CAT-FLNPs were prepared, which significantly enhanced the resistance of C2C12 cells to H2O2-induced injury in vitro. In vivo studies further revealed that HGF/CAT-FLNPs effectively alleviated hindlimb ischemia-induced gangrene, restored motor function, and promoted blood perfusion recovery in mice. Metabolomics analysis indicated that FLNPs didn't induce metabolic disturbances during gene transfection. In conclusion, FLNPs represent a versatile platform for multi-dimensional assisted gene delivery, significantly improving the efficiency of gene delivery and holding promise for effective synergistic treatment of lower limb ischemia using pHGF and pCAT.

Leveraging thiol-functionalized biomucoadhesive hybrid nanoliposome for local therapy of ulcerative colitis.

Directly administering medication to inflamed intestinal sites for treating ulcerative colitis (UC), poses significant challenges like retention time, absorption variability, side effects, drug stability, and non-specific delivery. Recent advancements in therapy to treat colitis aim to improve local drug availability that is enema therapy at the site of inflammation, thereby reducing systemic adverse effects. Nevertheless, a key limitation lies in enemas' inability to sustain medication in the colon due to rapid peristaltic movement, diarrhea, and poor local adherence. Therefore, in this work, we have developed site-specific thiolated mucoadhesive anionic nanoliposomes to overcome the limitations of conventional enema therapy. The thiolated delivery system allows prolonged residence of the delivery system at the inflamed site in the colon, confirmed by the adhesion potential of thiolated nanoliposomes using in-vitro and in-vivo models. To further provide therapeutic efficacy thiolated nanoliposomes were loaded with gallic acid (GA), a natural compound known for its antibacterial, antioxidant, and potent anti-inflammatory properties. Consequently, Gallic Acid-loaded Thiolated 2,6 DALP DMPG (GATh@APDL) demonstrates the potential for targeted adhesion to the inflamed colon, facilitated by their small size 100 nm and anionic nature. Therapeutic studies indicate that this formulation offers protective effects by mitigating colonic inflammation, downregulating the expression of NF-κB, HIF-1α, and MMP-9, and demonstrating superior efficacy compared to the free GA enema. The encapsulated GA inhibits the NF-κB expression, leading to enhanced expression of MUC2 protein, thereby promoting mucosal healing in the colon. Furthermore, GATh@APDL effectively reduces neutrophil infiltration and regulates immune cell quantification in colonic lamina propria. Our findings suggest that GATh@APDL holds promise for alleviating UC and addressing the limitations of conventional enema therapy.

Advanced nanoparticles in osteoarthritis treatment.

Osteoarthritis (OA) is the most prevalent degenerative joint disorder, affecting hundreds of millions of people globally. Current clinical approaches are confined to providing only symptomatic relief. Research over the past two decades has established that OA is not merely a process of wear and tear of the articular cartilage but involves abnormal remodelling of all joint tissues. Although many new mechanisms of disease have been identified in the past several decades, the efficient and sustainable delivery of drugs targeting these mechanisms in joint tissues remains a major challenge. Nanoparticles recently emerged as favoured delivery vehicles in OA treatment, offering extended drug retention, enhanced drug targeting, and improved drug stability and solubility. In this review, we consider OA as a disease affecting the entire joint and initially explore the pathophysiology of OA across multiple joint tissues, including the articular cartilage, synovium, fat pad, bone, and meniscus. We then classify nanoparticles based on their composition and structure, such as lipids, polymers, inorganic materials, peptides/proteins, and extracellular vesicles. We summarise the recent advances in their use for treatment and diagnosis of OA. Finally, we discuss the current challenges and future directions in this field. In conclusion, nanoparticle-based nanosystems are promising carriers that advance OA treatment and diagnosis.

Enhancing vaccine efficacy: Evaluating the superiority of cationic liposome-embedded squalene adjuvant against PCV2 infection.

Cationic liposome-embedded squalene (CLS) is a promising adjuvant that enhances antigen stability and mobility and improves immune response. This study compares the efficacy of a CLS-adjuvant porcine circovirus type 2 (PCV2) vaccine (CSV) with a conventional vaccine against PCV2. The CSV vaccine showed superior stability and was effective against PCV2-induced growth decline. It significantly increased serum immunoglobulin and cytokine levels, reduced serum PCV2 DNA, shortened the duration of viremia, and provided robust protection. CSV outperformed conventional vaccines, highlighting its potential for innovative vaccine development.

Smart Accumulating Dual-Targeting Lipid Envelopes Equipping Oncolytic Adenovirus for Enhancing Cancer Gene Therapeutic Efficacy.

Systemic delivery of oncolytic adenovirus (oAd) for cancer gene therapy must overcome several limitations such as rapid clearance from the blood, nonspecific accumulation in the liver, and insufficient delivery to the tumor tissues. In the present report, a tumor microenvironment-triggered artificial lipid envelope composed of a pH-responsive sulfamethazine-based polymer (PUSSM)-conjugated phospholipid (DOPE-HZ-PUSSM) and another lipid decorated with epidermal growth factor receptor (EGFR) targeting peptide (GE11) (GE11-DOPE) was utilized to encapsulate replication-incompetent Ad (dAd) or oAd coexpressing short-hairpin RNA (shRNA) against Wnt5 (shWnt5) and decorin (dAd/LP-GE-PS or oAd/LP-GE-PS, respectively). In vitro studies demonstrated that dAd/LP-GE-PS transduced breast cancer cells in a pH-responsive and EGFR-specific manner, showing a higher level of transduction than naked Ad under a mildly acidic pH of 6.0 in EGFR-positive cell lines. In vivo biodistribution analyses revealed that systemic administration of oAd/LP-GE-PS leads to a significantly higher level of intratumoral virion accumulation compared to naked oAd, oAd encapsulated in a liposome without PUSSM or EGFR targeting peptide moiety (oAd/LP), or oAd encapsulated in a liposome with EGFR targeting peptide alone (oAd/LP-GE) in an EGFR overexpressing MDA-MB-468 breast tumor xenograft model, showing that both pH sensitivity and EGFR targeting ability were integral to effective systemic delivery of oAd. Further, systemic administration of all liposomal oAd formulations (oAd/LP, oAd/LP-GE, and oAd/LP-GE-PS) showed significantly attenuated hepatic accumulation of the virus compared to naked oAd. Collectively, our findings demonstrated that pH-sensitive and EGFR-targeted liposomal systemic delivery of oAd can be a promising strategy to address the conventional limitations of oAd to effectively treat EGFR-positive cancer in a safe manner.

The influence and mechanism of fish collagen peptide and egg yolk lecithin on proliferation and lipid composition in feline adipocytes.

The influences of fish collagen peptide (FCP) and egg yolk lecithin (EYL) on the proliferation, fat accumulation and triglyceride content in feline adipocytes were investigated in this work, aiming at unveiling the mechanism of fat accumulation for cheek of feline animals. The lipogenic changes of adipocytes in the presence of FCP and EYL were determined by high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). The results demonstrated that FCP of 10 mg/mL had the strongest cell activity, with a relative increment rate of 156 ± 0.23%, and the triglyceride content reached 215.9 ± 3.86 mmol/L. By comparison, it was observed that an EYL concentration of 5 mg/mL elicited the highest cell activity, exhibiting a relative increment rate of 152 ± 0.60%, and the level of triglyceride content was noted to reached 256.56 ± 25.68 mmol/L. After the feline adipocytes were treated with different concentrations of two active substances, fat formation and lipid droplets were found by oil red O staining. Liposome analyses confirmed that the formation of lipid compounds was regulated by FCP and EYL through pathways involved in lipid metabolism, notably including inositol phosphate insulin resistance, and phosphatidylinositol signaling pathways. This regulation was found to enhance cell vitality and facilitate fat accumulation. These findings provide a new strategy for the development of nutritional and healthy products or foods that promote feline cheek.

Engineering small extracellular vesicles with multivalent DNA probes for precise tumor targeting and enhanced synergistic therapy.

Small extracellular vesicles (sEVs) have gained wide attention as efficient carriers for disease treatment. However, the proclivity of sEVs to be ingested by source cells is insufficient to accurately target specific sites, posing a challenge in realizing controlled targeting treatment. Here, we developed an engineered sEV nanocarrier capable of precise tumor targeting and enhanced synergistic therapy. Multivalent DNA probes, comprising abundant AS1411 aptamers and telomerase primers, were innovatively modified on the sEV membrane (M-D-sEV) for precise tumor targeting. To achieve synergistic therapy, gold nanorod-cerium oxide nanostructures (Au NRs-CeO2) and manganese dioxide nanosheets-doxorubicin (MnO2 NSs-DOX) were encapsulated into liposomes (Lip-Mat). Then M-D-sEV and Lip-Mat were fused together through membrane fusion to obtain nanocarriers. Owing to the multivalence of the probes, the surface of the nanocarriers was loaded with numerous aptamers, which greatly enhances their targeting ability and promotes the accumulation of drugs. When nanocarriers were ingested by tumor cells, telomerase and multivalent DNA probes triggered their aggregation, enhancing the therapeutic effect. Furthermore, under laser irradiation, Au NRs-CeO2 converted light into hyperthermia, thereby inducing the destruction of nanocarriers membrane. This process initiated a series of reactions involving glutathione and H2O2 consumption, as well as DOX release, ultimately achieving synergistic tumor therapy. In vitro and in vivo studies demonstrated the remarkable targeting ability of multivalent DNA probes and excellent therapeutic effect of this strategy. The engineered strategy of sEVs provide a promising approach for precise tumor therapy and hold great potential for the development of efficient, safe, and personalized drug delivery systems.

Preparation and characterization of niosomes for the delivery of a lipophilic model drug: comparative stability study with liposomes against phospholipase-A2.

Vesicular nanocarriers like niosomes and liposomes are widely researched for controlled drug delivery systems, with niosomes emerging as promising alternatives due to their higher stability and ease of manufacturing. This study aimed to develop and characterize a niosomal formulation for the encapsulation and sustained release of temozolomide (TMZ), a model lipophilic drug, and to compare the stability of niosomes and liposomes, with a particular focus on the behavior of their lipid bilayers. Niosomes were prepared using the thin-film hydration method, composed of Span 60 (Sorbitan monostearate), cholesterol, and soy lecithin in varying molar ratios. The study investigated critical properties such as drug loading capacity, release kinetics, and resistance to enzymatic degradation. The optimized formulation was analyzed for drug entrapment efficiency and stability against phospholipase A2 (PLA2) degradation. The optimized niosomal formulation, with a 4:2:1 molar ratio of Span 60: cholesterol, achieved a high TMZ entrapment efficiency of 73.23 ± 1.02% and demonstrated sustained drug release over 24 hours. In comparison, liposomes released their TMZ payload within 4 hours upon exposure to PLA2, while the niosomes maintained their release profile, indicating superior stability. Spectroscopic and thermal analysis confirmed successful drug encapsulation with no component incompatibilities.

A Dual-Function LipoAraN-E5 Coloaded with N4-Myristyloxycarbonyl-1-ß-d-arabinofuranosylcytosine (AraN) and a CXCR4 Antagonistic Peptide (E5) for Blocking the Dissemination of Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a hematological malignancy with a high recurrence rate. The interaction of chemokine receptor 4/chemokine ligand 12 (CXCR4/CXCL12) mediates homing and adhesion of AML cells in bone marrow, leading to minimal residual disease in patients, which brings a hidden danger for future AML recurrence. Ara-C is a nonselective chemotherapeutic agent against AML. Due to its short half-life and severe side effects, a lipid-like Ara-C derivative (AraN) was synthesized and a dual-function LipoAraN-E5 (135 nm, encapsulation efficiency 99%) was developed, which coloaded AraN and E5, a peptide of the CXCR4 antagonist. LipoAraN-E5 effectively improved the uptake, enhanced the inhibition of leukemia cell proliferation, migration, and adhesion to stromal cells in bone marrow, and mobilized the leukemia cells from bone marrow to peripheral blood via interfering with the CXCR4/CXCL12 axis. LipoAraN-E5 prolonged the plasma half-life of AraN (8.31 vs 0.56 h) and was highly enriched in peripheral blood (3.67 vs 0.05 µmol/g at 8 h) and bone marrow (379 vs 148 µmol/g at 24 h). LipoAraN-E5 effectively prevented the infiltration of leukemia cells in peripheral blood, bone marrow, spleen, and liver, prolonged the mice survival, and showed outstanding antineoplastic efficacy with negligible toxicity, which were attributed to the ingenious design of AraN, the use of a liposomal delivery carrier, and the introduction of E5. Our work revealed that LipoAraN-E5 may be a promising nanocandidate against AML.

Immune Implications of Cholesterol-Containing Lipid Nanoparticles.

The majority of clinically approved nanoparticle-mediated therapeutics are lipid nanoparticles (LNPs), and most of these LNPs are liposomes containing cholesterol. LNP formulations significantly alter the drug pharmacokinetics (PK) due to the propensity of nanoparticles for uptake by macrophages. In addition to readily engulfing LNPs, the high expression of cholesterol hydroxylases and reactive oxygen species (ROS) in macrophages suggests that they will readily produce oxysterols from LNP-associated cholesterol. Oxysterols are a heterogeneous group of cholesterol oxidation products that have potent immune modulatory effects. Oxysterols are implicated in the pathogenesis of atherosclerosis and certain malignancies; they have also been found in commercial liposome preparations. Yet, the in vivo metabolic fate of LNP-associated cholesterol remains unclear. We review herein the mechanisms of cellular uptake, trafficking, metabolism, and immune modulation of endogenous nanometer-sized cholesterol particles (i.e., lipoproteins) that are also relevant for cholesterol-containing nanoparticles. We believe that it would be imperative to better understand the in vivo metabolic fate of LNP-associated cholesterol and the immune implications for LNP-therapeutics. We highlight critical knowledge gaps that we believe need to be addressed in order to develop safer and more efficacious lipid nanoparticle delivery systems.

Ionic liquid combined with cationic liposome co-delivers microphthalmia-associated transcription factor small interfering RNA to regulate melanogenesis.

Suppressing allele-specific genes using small interfering RNAs (siRNAs) can effectively whiten skin by influencing cellular gene and protein expression. Topical delivery of siRNA is a promising alternative to injections for RNA interference. However, the barrier function of the skin hinders the effective penetration of siRNA. Here, we report, a novel approach to achieve the transdermal delivery of effective siRNA doses using a complementary synergistic strategy of an ionic liquid (IL) and cationic liposome (CL). Microphthalmia-associated transcription factor (MITF) siRNA molecules were formed through electrostatic adsorption of the IL and CL to form positively charged nanocomposites, which were named IL-CL/p-siM. IL-CL/p-siM has a particle size of 171.47 nm, ζ-potential of 29.94 mV, high encapsulation rate of 92.11 %, and pH-sensitive release properties. In vitro studies on porcine skin confirmed the additive/synergistic effect of this strategy in enhancing epidermal and dermal penetration. This combination enabled superior transfection efficiency and cell viability while inhibiting melanin synthesis in skin melanocytes by downregulating the expression of genes downstream of MITF, namely tyrosinase-related protein-1, tyrosinase, and tyrosinase-related protein-2, which are associated with the melanocortin 1 receptor. We also conducted clinical studies that demonstrated its potential in treating melasma and its anti-melanotic efficacy. To summarize, IL-CL/p-siM represents a simple, personalized, and scalable platform for effective local delivery of siRNA to treat skin complications.

A sustainable RP-HPLC method for concurrent estimation of capecitabine and celecoxib in liposomal formulation: Greenness and whiteness appraisal.

Liposomes have been reported for combination therapy due to their ability to carry both hydrophilic and lipophilic drugs together. The current investigation aims to develop a novel, eco-friendly, and sustainable reverse-phase high-performance liquid chromatography (RP-HPLC) method for the simultaneous quantification of capecitabine and celecoxib co-encapsulated in liposomes. The method reported herein uses a C18 column (4.6 × 250 mm2, 5 µm) and a mobile phase consisting of water, and acetonitrile/methanol in a ratio of 60:40, containing 0.1% formic acid in both the phases. The flow rate is maintained at 1 mL/min, with an injection volume of 10 µL in the gradient mode. Detection is set at λmax = 240 nm for capecitabine and 252 nm for celecoxib. The developed liposomes are mono-disperse with a surface potential of -6.93 mV. The average size of the liposomes is 142 nm. The percentage entrapment efficiency for capecitabine is 52.39 ± 0.94%, and for celecoxib, it is 77.13 ± 0.74%. The Analytical Greenness Metric of 0.61 and Analytical Eco-Scale Score of 75 signify the greenness of the developed method. Also, the Red-Green-Blue model shows excellent whiteness, with a score of 83.2. Thus, the developed method offers a reliable, accurate, precise, buffer-free, and environment-friendly RP-HPLC approach for the simultaneous analysis of capecitabine and celecoxib co-encapsulated in liposomes.

Moment analysis method for the determination of permeation kinetics of coumarin at lipid bilayers of liposomes by using capillary electrophoresis.

A method was developed for studying mass transfer kinetics at lipid bilayers of liposomes. Elution peaks of coumarin were measured by liposome electrokinetic chromatography (LEKC). Four types of phospholipids having different alkyl chains were used for preparing liposomes, which were used as pseudo-stationary phases in LEKC systems. Rate constants of permeation across lipid bilayers of liposomes or of adsorption at lipid membranes were determined by analyzing the first absolute and second central moments of the elution peaks measured by LEKC. The rate constants of permeation or adsorption tend to decrease with an increase in the carbon number of the alkyl chains of phospholipids. It was demonstrated that the moment analysis of elution peak profiles measured by LEKC is effective for determining lipid membrane permeability or adsorption kinetics. Compared with other conventional techniques, the method has some advantages for studying mass transfer kinetics at lipid bilayers. Solute permeation across or solute adsorption at real lipid bilayers of liposomes is analyzed. The principle of the method is the analysis of separation behavior in LEKC, which is different from that of the other ones. It is expected that the method contributes to the kinetic study of mass transfer at lipid bilayers from various perspectives.

A Comparative Review of Tocosomes, Liposomes, and Nanoliposomes as Potent and Novel Nanonutraceutical Delivery Systems for Health and Biomedical Applications.

Contemporary nutraceutical and biomedical sectors are witnessing fast progress in efficient product development due to the advancements in nanoscience and encapsulation technology. Nutraceuticals are generally defined as food substances, or a section thereof, that provide us with health benefits such as disease prevention and therapy. Nutraceutical and biomedical compounds as well as food supplements are a natural approach for attaining therapeutic outcomes with negligible or ideally no adverse effects. Nonetheless, these materials are susceptible to deterioration due to exposure to heat, oxygen, moisture, light, and unfavorable pH values. Tocosomes, or bilayered lyotropic vesicles, are an ideal encapsulation protocol for the food and nutraceutical industries. Biocompatibility, high entrapment capacity, storage stability, improved bioavailability, site specific delivery, and sustained-release characteristics are among the advantages of this nanocarrier. Similar to liposomal carriers and nanoliposomes, tocosomes are able to encapsulate hydrophilic and hydrophobic compounds separately or simultaneously, offering synergistic bioactive delivery. This manuscript describes different aspects of tocosome in parallel to liposome and nanoliposome technologies pertaining to nutraceutical and nanonutraceutical applications. Different properties of these nanocarriers, such as their physicochemical characteristics, preparation approaches, targeting mechanisms, and their applications in the biomedical and nutraceutical industries, are also covered.

A hierarchically acidity-unlocking nanoSTING stimulant enables cascaded STING activation for potent innate and adaptive antitumor immunity.

Rationale: Neoadjuvant chemotherapy (NAC) has been recognized as an indispensable strategy for advanced malignancies. Nevertheless, the enhancement of overall patient survival in NAC recipients has encountered challenges due to the limited sustainability of its efficacy and the inability to prevent postoperative tumor recurrence and metastasis. Methods: We devise a hierarchically unlocking nanoSTING stimulant liposome (AUG) as a neoadjuvant chemoimmunotherapy agent in the debulking of tumors prior to surgery and prevention of postoperative tumor recurrence and metastasis by simultaneously activating innate and adaptive antitumor immune responses. In the weakly acidic tumor microenvironment, the hydrazone bond within AUG is initially cleaved, leading to the release of a cyclic seven-membered ring containing tertiary amine that serve to activate the stimulator of interferon genes (STING) pathway. Following this, AUG undergoes degradation within lysosomes, facilitating the release of doxorubicin and ultimately inducing immunogenic cell death along with leakage of double-stranded DNA into the cytoplasm. Results: The hierarchically acidity-unlocking pattern enables cascaded STING activation, achieving over 90% tumor growth inhibition in subcutaneous xenograft model and preventing 75% of mice from postsurgical metastasis or recurrence when combined with immune checkpoint inhibitors. Conclusion: Our strategy highlights the potency of AUG as a neoadjuvant paradigm for presurgical tumor debulking and as a preventive measure against postoperative tumor recurrence and metastasis.

Neurobehavioral assessment of BMEDA by modified Irwin test in Sprague-Dawley rats.

The neurobehavioral assessment of N,N-bis(2-mercapatoethly)-N',N'-diethylenediamine (BMEDA), which can form a chelate with rhenium-188 (188Re) to produce the 188Re-BMEDA-liposome, was evaluated. The purpose of this study was to evaluate the potential neurobehavioral changes by using the functional observational battery observation procedures when intravenous injection of BMEDA to Sprague-Dawley rats. Rats were administered BMEDA at dose levels of 1, 2, and 5 mg/kg. No mortalities were observed. There are some observations related to BMEDA treatment found in the 5 mg/kg dose group at 10 min post-dose. Tremor was observed in one male rat and seven female rats. The increased respiration, vocalization, not easy to handle and/or loss of tone in the limb were observed in both males and females, and increased body temperature was observed in male animals. Based on the results, a single intravenous dose of BMEDA administered to rats resulted in increased respiration, vocalization, not easy to handle and/or loss of tone in the limb increasing at the dose level of 5 mg/kg. No neurobehavioral effects were noted after BMEDA administration up to the dose level of 2 mg/kg. The information of this study will provides a point of reference to design appropriately therapeutic studies for future human use.

Cardiac-targeted and ROS-responsive liposomes containing puerarin for attenuating myocardial ischemia-reperfusion injury.

Aim: This study aimed to construct an ischemic cardiomyocyte-targeted and ROS-responsive drug release system to reduce myocardial ischemia-reperfusion injury (MI/RI).Methods: We constructed thioketal (TK) and cardiac homing peptide (CHP) dual-modified liposomes loaded with puerarin (PUE@TK/CHP-L), which were expected to deliver drugs precisely into ischemic cardiomyocytes and release drugs in response to the presence of high intracellular ROS levels. The advantages of PUE@TK/CHP-L were assessed by cellular pharmacodynamics, in vivo fluorescence imaging and animal pharmacodynamics.Results: PUE@TK/CHP-L significantly inhibited apoptosis and ferroptosis in H/R-injured cardiomyocytes and also actively targeted ischemic myocardium. Based on these advantages, PUE@TK/CHP-L could significantly enhance the drug's ability to attenuate MI/RI.Conclusion: PUE@TK/CHP-L had potential clinical value in the precise treatment of MI/RI.

[Box: see text].

Encapsulation of lemongrass essential oil by bilayer liposomes based on pectin, gum Arabic, and carrageenan: Characterization and application in chicken meat preservation.

The volatile characteristics of lemongrass essential oil (LO) have seriously hindered its further application, and encapsulation it with multilayer modified liposomes may be an effective strategy to improve this dilemma. This study selected chitosan (CH) and three anionic polymers, pectin (P) / gum arabic (GA) / carrageenan (C), as the first and second coating polymers to modify nano liposomes (NL) by layer-by-layer electrostatic deposition, obtaining three bilayer liposomes, P-CH-NL, GA-CH-NL, and C-CH-NL as high-quality stabilized carriers of LO. The bilayer liposomes showed a dense membrane structure ranging from 110 to 150 nm uniformly, with good antioxidant properties. All bilayer liposomes had good stability during 28-day storage at 4 °C, while C-CH-NL performed relatively better inferred by smaller changes of size, PDI and Zeta potential. The total volatile base nitrogen (TVB-N) values of fresh chicken meat and a total number of bacterial colonies (TBC) experiments showed that GA-CH-NL and C-CH-NL could better retard the increase of volatile salt base nitrogen. All bilayer liposomes could delay the time for the total bacterial count to exceed 6 log CFU/g (from 7 days to 10 / 12 days). Therefore, the bilayer liposomes P-CH-NL, GA-CH-NL, and C-CH-NL may be promising natural preservatives for food products.

HER-2 Receptor and αvß3 Integrin Dual-Ligand Surface-Functionalized Liposome for Metastatic Breast Cancer Therapy.

Human epidermal growth factor receptor-2 (HER2)-positive breast cancer metastasis remains the primary cause of mortality among women globally. Targeted therapies have revolutionized treatment efficacy, with Trastuzumab (Trast), a monoclonal antibody, targeting HER2-positive advanced breast cancer. The tumor-homing peptide iRGD enhances the intratumoral accumulation and penetration of therapeutic agents. Liposomes serve as versatile nanocarriers for both hydrophilic and hydrophobic drugs. Gefitinib (GFB) is a potential anticancer drug against HER2-positive breast cancer, while Lycorine hydrochloride (LCH) is a natural compound with anticancer and anti-inflammatory properties. This study developed TPGS-COOH-coated liposomes co-loaded with GFB and LCH, prepared by the solvent injection method, and surface-functionalized with Trast and iRGD. The dual surface-decorated liposomes (DSDLs) were characterized for their particle size (PS), polydispersity index (PDI), zeta potential (ZP), surface chemistry, surface morphology, and their crystallinity during in-vitro drug release, drug encapsulation, and in-vitro cell line studies on SK-BR-3 and MDA-MB-231 breast cancer cells. The half-maximum inhibitory concentration (IC-50) values of single decorated liposomes (SDLs), iRGD-LP, and Trast-LP, as well as DSDLs (iRGD-Trast-LP) on SK-BR-3 cells, were 6.10 ± 0.42, 4.98 ± 0.36, and 4.34 ± 0.32 µg/mL, respectively. Moreover, the IC-50 values of SDLs and DSDLs on MDA-MB-231 cells were 15.12 ± 0.68, 13.09 ± 0.59, and 11.08 ± 0.48 µg/mL, respectively. Cellular uptake studies using confocal laser scanning microscopy (CLSM) showed that iRGD and Trast functionalization significantly enhanced cellular uptake in both cell lines. The wound-healing assay demonstrated a significant reduction in SDL and DSDL-treated MDA-MB-231 cell migration compared to the control. Additionally, the blood compatibility study showed minimal hemolysis (less than 5% RBC lysis), indicating good biocompatibility and biosafety. Overall, these findings suggest that TPGS-COOH-coated, GFB and LCH co-loaded, dual-ligand (iRGD and Trast) functionalized, multifunctional liposomes could be a promising therapeutic strategy for treating HER2-positive metastatic breast cancer.

Enhanced Antitumor Efficacy of Cytarabine and Idarubicin in Acute Myeloid Leukemia Using Liposomal Formulation: In Vitro and In Vivo Studies.

Background: Acute myeloid leukemia (AML) is the most common type of acute leukemia among adults with the recommend therapy of combination of cytarabine and idarubicin in the induction phase. The uncoordinated pharmacokinetics prevent adequate control of drug ratio following systemic administration. Therefore, the dual-loaded liposomes containing cytarabine and idarubicin for synergistic effects were proposed and investigated. Methods: The molar ratio of cytarabine and idarubicin for synergistic effects was investigated. The dual-loaded liposomes were prepared and characterized by particle size, zeta potential, encapsulation efficiency, cryo-Transmission electron microscopy (cryo-TEM), and in vitro stability. The in vitro cytotoxicity and cell uptake of liposomes were determined within CCRF-CEM cells. The PK experiments was carried out in male SD rats. The in vivo antitumor effect was carried out within CD-1 nude female mice. The antitumor mechanism of liposomes was investigated. Results: The synergistic molar ratios were found to be in the range of 20:1~40:1. The size distribution of the dual-loaded liposomes was approximately 100 nm with PDI ≤ 0.1, a zeta potential of approximately -30 mV, an entrapment efficiency of cytarabine and idarubicin of >95% with spherical structure and uniform distribution, and in vitro stability for 21 d. The drugs in the liposomes can be quickly uptaken by the leukemia cells. The PK experiments showed that the molar ratio of cytarabine to idarubicin in plasma was maintained at 30:1 within 4 h. The efficacy of liposomes was significantly enhanced. Conclusions: The dual-loaded liposomes containing cytarabine and idarubicin showed enhanced antitumor efficacy.