Preparation and characterization of Antarctic krill oil/quercetin co-loaded liposomes and their protective effect on oleic acid-induced steatosis and oxidative stress in vitro.

This study aims to introduce a new liposome to co-load Antarctic krill oil (AKO) and quercetin (QC) as a new delivery formulation to enrich the application of AKO and QC. The stability of liposomes could be increased by adding an appropriate quantity of soy lecithin (SL). Changes in the composition of the phospholipid membrane were strongly correlated with the stability and release capacity of loaded nutrients. SL2@QC/AKO-lips displayed a nearly spherical shape with higher oxidative stability and controlled the in vitro release performance of QC in simulated digestion. Moreover, in vitro studies indicated that new liposomes had no adverse effects on cell viability and could combine the physiological functions of AKO and QC to protect the HepG2 cells from oleic acid-induced steatosis and oxidative stress. The findings demonstrated that the AKO and QC co-loaded liposomes prepared with the addition of an appropriate quantity of SL had excellent loading efficiency of AKO/QC and good oxidative stability, security and functional activity.

Co-encapsulation of hydrophilic and hydrophobic drugs into niosomal nanocarrier for enhanced breast cancer therapy: In silico and in vitro studies.

Combination therapy has been considered one of the most promising approaches for improving the therapeutic effects of anticancer drugs. This is the first study that uses two different antioxidants in full-characterized niosomal formulation and thoroughly evaluates their synergistic effects on breast cancer cells. In this study, in-silico studies of hydrophilic and hydrophobic drugs (ascorbic acid: Asc and curcumin: Cur) interactions and release were investigated and validated by a set of in vitro experiments to reveal the significant improvement in breast cancer therapy using a co-delivery approach by niosomal nanocarrier. The niosomal nanoparticles containing surfactants (Span 60 and Tween 60) and cholesterol at 2:1 M ratio were prepared through the film hydration method. A systematic evaluation of nanoniosomes was carried out. The release profile demonstrated two phases (initial burst followed by sustained release) and a pH-dependent release schedule over 72 h. The optimized niosomal preparation displayed superior storage stability for up to 2 months at 4 °C, exhibiting extremely minor changes in pharmaceutical encapsulation efficiency and size. Free dual drugs (Asc + Cur) and dual-drug loaded niosomes (Niosomal (Asc + Cur)) enhanced the apoptotic activity and cytotoxicity and inhibited cell migration which confirmed the synergistic effect of co-encapsulated drugs. Also, significant up-regulation of p53 and Bax genes was observed in cells treated with Asc + Cur and Niosomal (Asc + Cur), while the anti-apoptotic Bcl-2 gene was down-regulated. These results were in correlation with the increase in the enzyme activity of SOD, CAT, and caspase, and the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) upon treatment with the mentioned drugs. Furthermore, these anti-cancer effects were higher when using Niosomal (Asc + Cur) than Asc + Cur. Histopathological examination also revealed that Niosomal (Asc + Cur) had a lower mitosis index, invasion, and pleomorphism than Asc + Cur. These findings indicated that niosomal formulation for co-delivery of Asc and Cur would offer a promising delivery system for an effective breast cancer treatment.

Oral delivery of pectin-chitosan hydrogels entrapping macrophage-targeted curcumin-loaded liposomes for the treatment of ulcerative colitis.

The oral delivery of anti-inflammatory drugs has been a promising strategy for enhancing the clinical efficacy of ulcerative colitis (UC) treatment strategies. However, achieving site specific drug delivery to colon tissues and target cells is a challenging task for formulation scientists. In this study, macrophages-targeted liposome-loaded pectin-chitosan hydrogels were developed for UC treatment via oral administration. Folate-functionalized cholesterol was synthesized as lipid membrane materials for the liposomes containing curcumin (CUR). The incorporation of the liposomal CUR within pectin-chitosan hydrogels resulted in a matrix that exhibited considerable sensitivity to colonic enzymes during in vitro release. The targeted delivery of hybrids was able to effectively reach macrophages. They also showed enhanced capability to downregulate TNF-α, IL-6, and IL-1ß in the lipopolysaccharide-induced Raw 264.7 cells model. DSS-induced mice modelshowed improved anti-UC effects, including accelerated mucosal repair and decreased inflammation and modulate the immune balance in the intestinal tissue of mice with colitis, which may be attributable to increased drug accumulation in the colonic lumen and improved internalization to target cells. Therefore, the incorporation of folate-modified liposomes containing CUR and pectin-chitosan physical hydrogels could potentially serve as a favorable approach for treating UC through an oral colon-targeted drug delivery system.

Magnetic Delivery of Antigen-Loaded Magnetic Liposomes for Active Lymph Node Targeting and Enhanced Anti-Tumor Immunity.

Therapeutic cancer vaccines offer the greatest advantage of enhancing antigen-specific immunity against tumors, particularly for immunogenic tumors, such as melanoma. However, clinical responses remain unsatisfactory, primarily due to inadequate T cell priming and the development of acquired immune tolerance. A major obstacle lies in the inefficient uptake of antigen by peripheral dendritic cells (DCs) and their migration to lymph nodes for antigen presentation. In this context, the magnetic delivery of antigen-loaded magnetic liposomes (Ag-MLs) to actively target lymph node, is proposed. These magnetic responsive liposomes contain soluble mouse melanoma lysate and iron oxide nanoparticles in the core, along with the immunostimulatory adjuvant CpG-1826 incorporated into the lipid bilayer. When applied through magnetic targeting in the mouse melanoma model, Ag-MLs accumulate significantly in the target lymph nodes. This accumulation results in increased population of active DCs in lymph nodes and cytotoxic T lymphocytes (CTLs) within tumors, correlating with effective tumor growth inhibition. Overall, this study demonstrates the potential of magnetic targeting as an effective strategy for delivering cancer vaccines and activating the immune response, offering a novel platform for cancer immunotherapies.

Synergistic Amplification of Ferroptosis with Liposomal Oxidation Catalyst and Gpx4 Inhibitor for Enhanced Cancer Therapy.

As a distinctly different way from apoptosis, ferroptosis can cause cell death through excessive accumulation of lipid peroxide (LPO) and show great potential for cancer therapy. However, efficient strategies for ferroptosis therapy are still facing great challenges, mainly due to insufficient endogenous H2 O2 or relatively high pH value for Fenton reaction-dependent ferroptosis, and the high redox level of tumor cells attenuates the oxidation therapy. Herein, an efficient lipid-based delivery system to load oxidation catalyst and glutathione peroxidase 4 (Gpx4) inhibitor is orchestrated, intending to amplify Fenton reaction-independent ferroptosis by bidirectional regulation of LPO accumulation. Ferric ammonium citrate (FAC), Gpx4 inhibitor sorafenib (SF), and unsaturated lipids are constructed into mPEG2K -DSPE-modified liposomes (Lip@SF&FAC). Influenced by the high level of intratumoral glutathione, FAC can be converted into Fe2+ , and subsequently the formed iron redox pair (Fe2+ /Fe3+ ) catalyzes unsaturated phospholipids of liposomes into LPO via a Fenton reaction-independent manner. Meanwhile, SF can downregulate LPO reduction by inhibiting Gpx4 activation. In vitro and in vivo antitumor experiments show that Lip@SF&FAC induces massive LPO accumulation in tumor cells and ultimately exhibits strong tumor-killing ability with negligible side effect. Consequently, this two-pronged approach provides a new ferroptosis strategy for predominant LPO accumulation and enhanced cancer therapy.

Promising Nanomedicines of Shikonin for Cancer Therapy.

Malignant tumor, the leading cause of death worldwide, poses a serious threat to human health. For decades, natural product has been proven to be an essential source for novel anticancer drug discovery. Shikonin (SHK), a natural molecule separated from the root of Lithospermum erythrorhizon, shows great potential in anticancer therapy. However, its further clinical application is significantly restricted by poor bioavailability, adverse effects, and non-selective toxicity. With the development of nanotechnology, nano drug delivery systems have emerged as promising strategies to improve bioavailability and enhance the therapeutic efficacy of drugs. To overcome the shortcoming of SHK, various nano drug delivery systems such as liposomes, polymeric micelles, nanoparticles, nanogels, and nanoemulsions, were developed to achieve efficient delivery for enhanced antitumor effects. Herein, this review summarizes the anticancer pharmacological activities and pharmacokinetics of SHK. Additionally, the latest progress of SHK nanomedicines in cancer therapy is outlined, focusing on long circulation, tumor targeting ability, tumor microenvironment responsive drug release, and nanosystem-mediated combination therapy. Finally, the challenges and prospects of SHK nanomedicines in the future clinical application are spotlighted.

Silymarin Encapsulated Liposomal Formulation: An Effective Treatment Modality against Copper Toxicity Associated Liver Dysfunction and Neurobehavioral Abnormalities in Wistar Rats.

Wilson's disease causes copper accumulation in the liver and extrahepatic organs. The available therapies aim to lower copper levels by various means. However, a potent drug that can repair the damaged liver and brain tissue is needed. Silymarin has hepatoprotective, antioxidant, and cytoprotective properties. However, poor oral bioavailability reduces its efficacy. In this study, a "thin film hydration method" was used for synthesizing silymarin-encapsulated liposome nanoparticles (SLNPs) and evaluated them against copper toxicity, associated liver dysfunction and neurobehavioral abnormalities in Wistar rats. After copper toxicity induction, serological and behavioral assays were conducted to evaluate treatment approaches. Histological examination of the diseased rats revealed severe hepatocyte necrosis and neuronal vacuolation. These cellular degenerations were mild in rats treated with SLNPs and a combination of zinc and SLNPs (ZSLNPs). SLNPs also decreased liver enzymes and enhanced rats' spatial memory significantly (p = 0.006) in the diseased rats. During forced swim tests, SLNPs treated rats exhibited a 60-s reduction in the immobility period, indicating reduced depression. ZSLNPs were significantly more effective than traditional zinc therapy in decreasing the immobility period (p = 0.0008) and reducing liver enzymes, but not in improving spatial memory. Overall, SLNPs enhanced oral silymarin administration and managed copper toxicity symptoms.

TRAIL mediated apoptosis ruling and anticancer trigger by fine-tuned nano spheres of Fagonia cretica methanolic extracts as novel cancer regime.

Fagonia cretica L. is a tropical plant of family Zygophyllaceae with wide range of medicinally important secondary metabolites. The low cellular uptake of the polar compounds in the extract of the plant limits its biological application. In present study efficacy of F. cretica modified bioactive nano-formulations for in vitro modulation of TRAIL mediated extrinsic apoptotic pathway as cancer therapy was investigated. F. cretica methanolic extracts were formulated at nano-scale for green synthesis of silver nanoparticles, albumin conjugation and liposomes encapsulation to enhance targeted bioactivity against cancer. Physical characterization of the synthesized nanoparticles was done by SEM, EDX and Zeta potential analyzer. In vitro cell viability assay MTT was done for MCF-7, Hep-2, HUH-7 and HCEC cell lines. Relative expression variation of the apoptotic pathway-associated genes was done by qRT-PCR. SEM revealed spherical shape of 56.62 ± 8.04, 143 ± 11.54 and 83.36 ± 38.73 nm size and zeta potential - 18.6, - 15.5 and - 18.3 mV for liposomes, silver and albumin nanoparticles. Silver nanoparticles showed highest anticancer activity in vitro than albumin and liposomes nanoparticles with IC50 0.101 ± 0.004, 0.177 ± 0.03 and 0.434 ± 0.022 mg/mL in MCF-7, Hep-2 and HUH-7 respectively. F. cretica albumin and silver nanoparticles upregulated the in vitro TRAIL, DR4, DR5 and FADD gene expression at statistically significant levels in Hep-2 cell lines. Nano-formulations of F. cretica proved therapeutically important biomolecules in vitro. The hypothesized modulation of extrinsic apoptosis pathway genes through the plant nanoparticles proved novel medicinal options for effective treatment of cancer and enhancing the bioavailability of the active plant metabolites.

Amphiphilic Dendrimer Doping Enhanced pH-Sensitivity of Liposomal Vesicle for Effective Co-delivery toward Synergistic Ferroptosis-Apoptosis Therapy of Hepatocellular Carcinoma.

Ferroptosis, characterized by the accumulation of reactive oxygen species and lipid peroxides, has emerged as an attractive strategy to reverse drug resistance. Of particular interest is the ferroptosis-apoptosis combination therapy for cancer treatment. Herein, a nanoplatform is reported for effective co-delivery of the anticancer drug sorafenib (S) and the ferroptosis inducer hemin (H), toward synergistic ferroptosis-apoptosis therapy of advanced hepatocellular carcinoma (HCC) as a proof-of-concept study. Liposome is an excellent delivery system; however, it is not sufficiently responsive to the acidic tumor microenvironment (TME) for tumor-targeted drug delivery. The pH-sensitive vesicles are therefore developed (SH-AD-L) by incorporating amphiphilic dendrimers (AD) into liposomes for controlled and pH-stimulated release of sorafenib and hemin in the acidic TME, thanks to the protonation of numerous amine functionalities in AD. Importantly, SH-AD-L not only blocked glutathione synthesis to disrupt the antioxidant system, but also increased intracellular Fe2+ and ·OH concentrations to amplify oxidative stress, both of which contribute to enhanced ferroptosis. Remarkably, high levels of ·OH also augmented sorafenib-mediated apoptosis in tumor cells. This study demonstrates the efficacy of ferroptosis-apoptosis combination therapy, as well as the promise of the AD-doped TME-responsive vesicles for drug delivery in combination therapy to treat advanced HCC.

Controlled Delivery of Vancomycin from Collagen-tethered Peptide Vehicles for the Treatment of Wound Infections.

Despite the great promise of antibiotic therapy in wound infections, antibiotic resistance stemming from frequent dosing diminishes drug efficacy and contributes to recurrent infection. To identify improvements in antibiotic therapies, new antibiotic delivery systems that maximize pharmacological activity and minimize side effects are needed. In this study, we developed elastin-like peptide and collagen-like peptide nanovesicles (ECnVs) tethered to collagen-containing matrices to control vancomycin delivery and provide extended antibacterial effects against methicillin-resistant Staphylococcus aureus (MRSA). We observed that ECnVs showed enhanced entrapment efficacy of vancomycin by 3-fold as compared to liposome formulations. Additionally, ECnVs enabled the controlled release of vancomycin at a constant rate with zero-order kinetics, whereas liposomes exhibited first-order release kinetics. Moreover, ECnVs could be retained on both collagen-fibrin (co-gel) matrices and collagen-only matrices, with differential retention on the two biomaterials resulting in different local concentrations of released vancomycin. Overall, the biphasic release profiles of vancomycin from ECnVs/co-gel and ECnVs/collagen more effectively inhibited the growth of MRSA for 18 and 24 h, respectively, even after repeated bacterial inoculation, as compared to matrices containing free vancomycin, which just delayed the growth of MRSA. Thus, this newly developed antibiotic delivery system exhibited distinct advantages for controlled vancomycin delivery and prolonged antibacterial activity relevant to the treatment of wound infections.

Effect of multifactorial free and liposome-coated of bay laurel (Laurus nobilis) and rosemary (Salvia rosmarinus) extracts on the behavior of Listeria monocytogenes and Vibrio parahaemolyticus in silver carp (Hypophthalmichthys molitrix) stored at 4 °C.

In this study, the effect of bay laurel (Laurus nobilis) (LE) and rosemary (Salvia rosmarinus) (RE) extracts, in two free forms and loaded with liposome, on the behavior of Listeria monocytogenes and Vibrio parahaemolyticus in silver carp (Hypophthalmichthys molitrix) minced, were examined. After extraction, the extracts were evaluated for phenolic, flavonoid, and antibacterial compounds (determination of MIC and MBC). The treatments studied included control treatment, treatments containing 1 and 1.5% of free extracts, and treatments containing 1 and 1.5% of liposome-coated extracts of LE and RE which were examined at times of 0, 4, 8, and 12 days with 3 replications. The findings indicated that the amount of flavonoid and phenolic compounds and the results of antibacterial tests (MIC and MBC tests) in RE extract were more favorable than LE extract. The aqueous extract of rosemary had higher levels of phenolic (344.66 mg gallic acid/g extract) and flavonoid (245.33 mg Catechin/g extract) compounds compared to the bay laurel extract (257.66 mg gallic acid/g extract) and (151.26 mg Catechin/g extract) respectively. The results of the behavior of L. monocytogenes and V. parahaemolyticus in fish showed that with increasing the storage time at 4 °C, these parameters increased, but in the treatment containing the coated forms of LE and RE extracts (concentration 1.5%), changes were significantly slower than other treatments. According to the obtained results, it can be concluded that in general, adding extracts of bay laurel and rosemary in a concentration of 1.5% reduces the proliferation of bacteria that cause food poisoning.

Cyclovirobuxine D Brain-Targeted Liposomes Improve Cerebral Ischemia-Reperfusion Injury via Anti-Oxidant Stress and Activating Autophagy.

One of the main issues faced by nervous system diseases is that drugs are difficult to enter the brain. The previous study suggested that Cyclovirobuxine D (CVBD) encapsulated in Angiopep-conjugated Polysorbate 80-Coated Liposomes showed a better brain targeting by intranasal administration. Therefore, this study concentrated on the protection and mechanism of CVBD brain-targeted liposomes in treating CIRI. Middle cerebral artery occlusion-reperfusion induced CIRI model rats to explore the protective effect of CVBD brain-targeted liposome on CIRI. Moreover, the protective effect of CVBD liposomes on OGD/R-injured HT22 cells was examined by cell fusion degree, cell proliferation curve and cell viability. OGD/R-injured HT22 cell was infected by mRFP-GFP-LC3 adenovirus. The autophagosome and autophagy flow were observed by laser confocal microscopy, and autophagy-related protein expressions were analyzed by Western blot. The classic autophagy inhibitor, chloroquine, was used to explore the autophagy-regulatedmechanism of CVBD brain-targeted liposomes in treating CIRI. CVBD liposomes increased cell viability and decreased ROS level, improved oxidative stress protein expressions and activated autophagy in vitro. Furthermore, CVBD liposomes reversed the decrease of cell viability, increase of ROS level, and reduction of protein expressions associated with anti-oxidative stress and autophagy induced by chloroquine. Collectively, CVBD liposomes inhibited CIRI via regulating oxidative stress and enhancing autophagy level in vivo and in vitro.

Toxin-Enabled "On-Demand" Liposomes for Enhanced Phototherapy to Treat and Protect against Methicillin-Resistant Staphylococcus aureus Infection.

An effective therapeutic strategy against methicillin-resistant Staphylococcus aureus (MRSA) that does not promote further drug resistance is highly desirable. While phototherapies have demonstrated considerable promise, their application toward bacterial infections can be limited by negative off-target effects to healthy cells. Here, a smart targeted nanoformulation consisting of a liquid perfluorocarbon core stabilized by a lipid membrane coating is developed. Using vancomycin as a targeting agent, the platform is capable of specifically delivering an encapsulated photosensitizer along with oxygen to sites of MRSA infection, where high concentrations of pore-forming toxins trigger on-demand payload release. Upon subsequent near-infrared irradiation, local increases in temperature and reactive oxygen species effectively kill the bacteria. Additionally, the secreted toxins that are captured by the nanoformulation can be processed by resident immune cells to promote multiantigenic immunity that protects against secondary MRSA infections. Overall, the reported approach for the on-demand release of phototherapeutic agents into sites of infection could be applied against a wide range of high-priority pathogens.

Carboxymethyl Chitosan Modified Oxymatrine Liposomes for the Alleviation of Emphysema in Mice via Pulmonary Administration.

Pulmonary emphysema is a fatal lung disease caused by the progressive thinning, enlargement and destruction of alveoli that is closely related to inflammation and oxidative stress. Oxymatrine (OMT), as a bioactive constituent of traditional Chinese herbal Sophora flavescens, has great potential to alleviate pulmonary emphysema via its anti-inflammatory and antioxidative activities. Pulmonary administration is the most preferable way for the treatment of lung diseases. To improve the in vivo stability and pulmonary retention of OMT, OMT-loaded liposome with carboxymethyl chitosan (CMCS) modification was developed. The CMCS was modified on the surface of OMT liposomes via electrostatic attraction and covalent conjugation to obtain Lipo/OMT@CMCS and CMCS-Lipo/OMT, respectively. A porcine pancreatic elastase (PPE)-induced emphysema mice model was established to evaluate the alleviation effects of OMT on alveolar expansion and destruction. CMCS-modified liposomal OMT exhibited superior ameliorative effects on emphysema regardless of the preparation methods, and higher sedimentation and longer retention in the lung were observed in the CMCS-Lipo group. The mechanisms of OMT on emphysema were related to the downregulation of inflammatory cytokines and the rebalancing of antioxidant/oxidation via the Nrf2/HO-1 and NF-κB/IκB-α signaling pathways, leading to reduced cell apoptosis. Moreover, the OMT liposomal preparations further enhanced its anti-inflammatory and antioxidative effects. In conclusion, pulmonary administration of OMT is a potential strategy for the treatment of emphysema and the therapeutic effects can be further improved by CMCS-modified liposomes.

The relationship between the structure and functionality of essential PUFA delivery systems based on sodium caseinate with phosphatidylcholine liposomes without and with a plant antioxidant: an in vitro and in vivo study.

The aim of this work was to establish the main relationship between the structure and functionality of supramolecular complexes formed by sodium caseinate (SC) with phosphatidylcholine (PC) liposomes filled with fish oil (FO) to an equal mass ratio of n-3 to n-6 polyunsaturated fatty acids (PUFA) in the absence and presence of one of the most effective plant antioxidants, namely the essential oil of clove buds (EOC). The functionality of the supramolecular complexes (SC-PC-FO and SC-PC-FO-EOC) was considered from the point of view of the possibility of their use as effective delivery systems for long-chain n-3 PUFAs (eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids from FO). The laser light scattering method was used in the static, dynamic and electrophoretic modes to characterize the structure and thermodynamic parameters of the supramolecular complexes in an aqueous medium. It was found that the SC-PC-FO and SC-PC-FO-EOC complex particles had the following similar properties: nanosize; a spherical shape; 100% solubility in an aqueous medium (pH 7.0, ionic strength = 0.001 M); a high encapsulating ability of SC (up to 70%) in relation to the studied liposomes; and a high protective ability relative to lipid autooxidation (up to 96% on the 20th day of storage at room temperature in light). In addition, a sequential transformation of both the structural and thermodynamic parameters has been observed for the complex particles under in vitro simulated gastrointestinal (GI) conditions in accordance with the INFOGEST protocol. A greater release of the encapsulated lipids from the enzymatically hydrolyzed complex particles was observed at the small intestine stage compared to their release at the gastric stage. These data were in good agreement with those on the assessment of the bioavailability of the target PUFAs in in vivo experiments based on the chronic intake of aqueous solutions of the complexes (both SC-PC-FO and SC-PC-FO-EOC) by experimental mice for 92 days. Liver lipid profiles of the mice, obtained by gas-liquid chromatography, showed the following: (i) an almost twofold increase in the DHA content as compared with that of the control; (ii) an almost threefold decrease in the mass ratio of arachidonic acid (AA) (C20:4 n-6) to DHA (C22:6 n-3) compared to that of the control due to both a significant decrease in the AA content and a simultaneous pronounced increase in the DHA content; and (iii) an almost twofold decrease in the mass ratio of the total amounts of n-6 to n-3 PUFAs compared to that of the control.

Preclinical evaluation of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B.

Safe and effective vaccines are needed to end the COVID-19 pandemic. Here, we report the preclinical development of a lipid nanoparticle­formulated SARS-CoV-2 mRNA vaccine, PTX-COVID19-B. PTX-COVID19-B was chosen among three candidates after the initial mouse vaccination results showed that it elicited the strongest neutralizing antibody response against SARS-CoV-2. Further tests in mice and hamsters indicated that PTX-COVID19-B induced robust humoral and cellular immune responses and completely protected the vaccinated animals from SARS-CoV-2 infection in the lung. Studies in hamsters also showed that PTX-COVID19-B protected the upper respiratory tract from SARS-CoV-2 infection. Mouse immune sera elicited by PTX-COVID19-B vaccination were able to neutralize SARS-CoV-2 variants of concern, including the Alpha, Beta, Gamma, and Delta lineages. No adverse effects were induced by PTX-COVID19-B in either mice or hamsters. Based on these results, PTX-COVID19-B was authorized by Health Canada to enter clinical trials in December 2020 with a phase 2 clinical trial ongoing.

Comprehensive review on use of phospholipid based vesicles for phytoactive delivery.

Plant-derived phytoconstituents are well known for their therapeutic potential. It has been experimentally demonstrated that whole-plant extract or isolated phytoconstituents reveal various therapeutic potentials like hepatoprotective, antimicrobial, neuroprotective, antitumor, antioxidant, skin protectives, etc. Although these phytoconstituents have potential therapeutic benefits, their use is limited due to their poor bioavailability, stability in biological fluids, and authentication issues. These continue to be an open problem that affects the application of these valuable ancient herbal herbs in the effective treatment and management of various disease conditions. A potential solution to these difficult problems could be the loading of phytoactives in phospholipid-based vesicular systems. Phospholipid-based vesicles like liposomes, phytosomes, ethosomes as well as transfersomes were effectively utilized recently to solve drawbacks and for effective delivery of phytoactives. Several landmark studies observed better therapeutic efficacy of phytoactive loaded vesicles compared to conventional drug delivery. Thus phospholipid-based vesicles mediated phytoactive delivery is a recently developed promising and attractive strategy for better therapeutic control on disease conditions. The present short review highlights recent advances in herbal bioactive loaded phospholipid-based vesicles.

Preparation, Characterization, and Anticancer Effects of Capsaicin-Loaded Nanoliposomes.

BACKGROUND: Medicinal plants have proven their value as a source of molecules with therapeutic potential, and recent studies have shown that capsaicin has profound anticancer effects in several types of human cancers. However, its clinical use is handicapped due to its poor pharmacokinetics. This study aims to enhance capsaicin's pharmacokinetic properties by loading the molecule into nanoliposomes model and testing its anticancer activity. METHODS: Nanoliposomes were prepared using the thin-film method, and characteristics were examined followed by qualitative and quantitative analyses of encapsulation efficiency and drug loading using HPLC at different lipid/capsaicin ratios. Cell viability assay (MTT) was used to determine IC50. RESULTS: Capsaicin-loaded nanoliposomes showed optimum characteristics of morphology, particle size, zeta potential, and stability. In vitro anticancer activity of capsaicin and capsaicin-loaded nanoliposomes were compared against MCF7, MDA-MB-231, K562, PANC1, and A375 cell lines. Capsaicin-loaded nanoliposomes showed significant improvement in anticancer activity against cancers cell lines studied (p < 0.001), with increased selectivity against cancer cells compared to capsaicin. CONCLUSION: The encapsulated capsaicin nanoliposomes produced an improvement in pharmacokinetics properties, enhancing the anticancer activity and selectivity compared with capsaicin. This model seems to offer a potential for developing capsaicin formulations for the prevention and treatment of cancer.

Thymoquinone Lipid Nanoparticles Cut the Gordian Knots of Depression via Neuroprotective BDNF and Downregulation of Neuro-inflammatory NF-κB, IL-6, and TNF-α in LPS Treated Rats.

BACKGROUND: In over 300 million clinical cases, antidepressant drugs seem to provide only symptomatic relief and limited protection in life-threatening depressive events. OBJECTIVES: To compare neuronal-signaling mechanism and neuroprotective roles of Thymoquinone (TQ) suspension and its SLN (TQSLN) against standard antidepressant drug fluoxetine. METHODS: This research investigated in-silico docking at NF-KB p50 active site, CLSM based gut permeation, screening of antidepressant activities and neurosignaling pathways involved. RESULTS: As compared to fluoxetine, TQ reporteda significantly better docking score (-6.83 v/s -6.22) and a better lower free binding energy of (-34.715 Kcal/mol v/s -28.537 Kcal/mol). While poorly oral bioavailable and P-gp substrate TQ reported approximately 250% higher gut permeation if delivered as TQSLN formulation. In locomotor studies, as compared to TQS, TQSLN favored more prominent (p< 0.010) elevation in average time, horizontalactivity, average-velocity, and total-movement with reduced rest time LPS treated groups. However, in the tail suspension test, TQSLN significantly reduced immobility time (p<0.010). Similarly, In the modified force swimming test, TQSLN also significantly reduced immobility time (p<0.010), but swimming time (p<0.010) and climbing time (p<0.050) were significantly elevated. Subsequently, TQSLN reported significantly elevated neuroprotective BDNF (p<0.010) as well as hippocampal 5HT/TRP; accompanied with reduced levels of hippocampal inflammatory markers TNF-α (p<0.001) and IL-6 (p<0.010) as well as lower kynurenine and tryptophan ratio (KYN/TRP). Similarly, the hippocampal CA1 region further revealed TQSL more predominantly attenuated NF-kB nuclear translocation in the brain. CONCLUSION: Despite the poor bioavailability of TQ, TQSLN potentially attenuates neuroinflammatory transmitters and favors BDNF to modulate depressive neurobehavioral states.

Thermal-sensitive lipid nanoparticles potentiate anti-PD therapy through enhancing drug penetration and T lymphocytes infiltration in metastatic tumor.

The response rate of anti-PD therapy in most cancer patients remains low. Therapeutic drug and tumor-infiltrating lymphocytes (TILs) are usually obstructed by the stromal region within tumor microenvironment (TME) rather than distributed around tumor cells, thus unable to induce the immune response of cytotoxic T cells. Here, we constructed the cationic thermosensitive lipid nanoparticles IR780/DPPC/BMS by introducing cationic NIR photosensitizer IR-780 iodide (IR780) modified lipid components, thermosensitive lipid DPPC and PD-1/PD-L1 inhibitor BMS202 (BMS). Upon laser irradiation, IR780/DPPC/BMS penetrated into deep tumor, and reduced cancer-associated fibroblasts (CAFs) around tumor cells to remodel the spatial distribution of TILs in TME. Interestingly, the cationic IR780/DPPC/BMS could capture released tumor-associated antigens (TAAs), thereby enhancing the antigen-presenting ability of DCs to activate cytotoxic T lymphocytes. Moreover, IR780/DPPC/BMS initiated gel-liquid crystal phase transition under laser irradiation, accelerating the disintegration of lipid bilayer structure and leading to the responsive release of BMS, which would reverse the tumor immunosuppression state by blocking PD-1/PD-L1 pathway for a long term. This combination treatment can synergistically exert the antitumor immune response and inhibit the tumor growth and metastasis.