Starch as a smart, cheap, and green gatekeeper for the controlled release of propyl gallate from antioxidant biodegradable packaging films.

Oxidative rancidity of food products and massive consumption of plastic packaging have put the necessity in manufacturing novel antioxidant biodegradable packaging films. A comprehensive investigation was conducted on starch/poly(butylene adipate-co-terephthalate) (PBAT) antioxidant blown films, in which starch acted as a gatekeeper for the controlled release of propyl gallate (PG). PG was well integrated into the matrices and bound to starch molecules by hydrogen bonding. All films showed strong anti-ultraviolet performance, and higher oxygen barrier than the traditional polyethylene film. Increasing starch proportions promoted the swelling of films and the release of PG, thereby causing higher antioxidant activity at the same contact time to free radical solutions. Similar polarity made PG prone to partition and rapid migration into the food simulants with higher ethanol concentration and the high-fat-content peanut butter. The film with 20:80 w/w starch/PBAT proportion and 3% w/w PG content effectively suppressed the oxidation of peanut butter within 300-day storage. Findings demonstrated this strategy for manufacturing starch/PBAT antioxidant films as a long-term active packaging in food industry.

Safety of a feed additive consisting of propyl gallate for all animal species (FEFANA ABL).

Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety of propyl gallate as a technological feed additive for all animal species. In its previous opinions on the safety and efficacy of the product, the FEEDAP Panel could not conclude on a safe level of propyl gallate for cats and on the safety for the consumer. Based on the new data provided, the FEEDAP Panel concluded that propyl gallate at a maximum concentration of 71 mg/kg complete feed is safe for cats. Propyl gallate is considered safe for the consumer when used in complete feed for all animal species at the concentrations considered safe for the target species.

Propyl gallate exposure affects the mouse 2-cell stage embryonic development through inducing oxidative stress and autophagy.

Propyl gallate (PG), owing to its exceptional antioxidant properties, is extensively used in industries such as food processing. The potential harmful impacts of PG have sparked concern among people. It has been reported that exposure of PG has certain reproductive toxicity, which can affect the maturation of mouse oocytes and induce testicular dysfunction. However, its impact on early embryonic development is still unclear. In this study, we explored the toxic effects and potential mechanisms of PG on mouse 2-cell stage embryonic development. The results showed that exposure of PG can decrease the development of 2-cell stage embryos and repress the development of 4-cell stage embryos. Further study found that PG could induce intracellular oxidative stress and the accumulation of DNA damage in 2-cell stage embryos. Moreover, exposure of PG impaired the function of mitochondria and lysosomes in 2-cell stage embryos, thereby triggering the occurrence of autophagy. In addition, exposure of PG altered the epigenetic modification of 2-cell stage embryos, displaying a decreased level of DNA methylation and an increased level of H3K4me3. In summary, our results indicated that exposure of PG can damage the development of mouse 2-cell stage embryos by inducing oxidative stress, DNA damage, and autophagy, and altering epigenetic modification.

Propyl gallate induces human pulmonary fibroblast cell death through the regulation of Bax and caspase-3.

Propyl gallate (PG) has been found to exert an inhibitory effect on the growth of different cell types, including lung cancer cells. However, little is known about the cytotoxicological effects of PG specifically on normal primary lung cells. The current study examined the cellular effects and cell death resulting from PG treatment in human pulmonary fibroblast (HPF) cells. DNA flow cytometry results demonstrated that PG (100-1,600 µM) had a significant impact on the cell cycle, leading to G1 phase arrest. Notably, 1,600 µM PG slightly increased the number of sub-G1 cells. Additionally, PG (400-1,600 µM) resulted in the initiation of cell death, a process that coincided with a loss of mitochondrial membrane potential (MMP; ΔΨm). This loss of MMP (ΔΨm) was evaluated using a FACS cytometer. In PG-treated HPF cells, inhibitors targeting pan-caspase, caspase-3, caspase-8, and caspase-9 showed no significant impact on the quantity of annexin V-positive and MMP (ΔΨm) loss cells. The administration of siRNA targeting Bax or caspase-3 demonstrated a significant attenuation of PG-induced cell death in HPF cells. However, the use of siRNAs targeting p53, Bcl-2, or caspase-8 did not exhibit any notable effect on cell death. Furthermore, none of the tested MAPK inhibitors, including MEK, c-Jun N-terminal kinase (JNK), and p38, showed any impact on PG-induced cell death or the loss of MMP (ΔΨm) in HPF cells. In conclusion, PG induces G1 phase arrest of the cell cycle and cell death in HPF cells through apoptosis and/or necrosis. The observed HPF cell death is mediated by the modulation of Bax and caspase-3. These findings offer insights into the cytotoxic and molecular effects of PG on normal HPF cells.

Chemical analysis of n-propyl gallate used as pre-treatment for resin-dentin bond strength: In vitro study.

This study aimed to evaluate the effect of n-propyl gallate as pre-treatment for resin-dentin bond strength. The dentin pre-treatments evaluated included propyl gallate of concentrations 0.1% (w/v), 1.0% (w/v), and 10.0% (w/v), as well as glutaraldehyde 5.0% (v/v), and distilled water as a control treatment. Dentin specimens were prepared for Fourier Transformed Infrared Spectroscopy (FT-IR) (n = 3/pre-treatment). Pre-treatments were actively applied to dentin blocks before performing the adhesive procedure to composite resin. Microtensile bond strength to dentin (µTBS) (n = 8/pre-treatment) was determined after 24 h and 6 months of storage. Data were submitted to a two-way ANOVA, followed by Tukey's post hoc test. As for FT-IR, propyl gallate 1%-treated specimens presented higher water, carbonate, collagen, and amide absorbance rates compared to other tested groups, while specimens pre-treated with glutaraldehyde and distilled water presented similar absorbance curves. Regarding µTBS, all concentrations of propyl gallate resulted in statistically significant higher bond strength values than distilled water at 24 h. After 6 months of storage, propyl gallate 0.1% was the only group that maintained µTBS over time. Propyl gallate 0.1% might be a suitable dentinal pre-treatment due to being able to present chemical bonds with demineralized dentin and providing resin-dentin bond stability after 6 months of storage.

Ce(IV)-coordinated organogel-based assay for on-site monitoring of propyl gallate with turn-on fluorescence signal.

Propyl gallate (PG) is a commonly used synthetic phenolic antioxidant in foodstuffs and industrial products. Due to the potential health risk of PG, rapid and on-site detection in food and environment samples are important to guarantee human health. Herein, we demonstrated rapid monitoring of PG by a fluorescence turn-on strategy based on a specific fluorogenic reaction between PG and polyethyleneimine (PEI). Specifically, Ce4+ with oxidase-mimicking activity oxidized PG to its oxides, which then reacted with PEI through the Michael addition to generate the fluorescent compound. The proposed fluorogenic reaction had good specificity for PG, which could distinguish PG from other phenolic antioxidants and interferences. Furthermore, portable and low-cost organogel test kits were prepared using poly(ethylene glycol) diacrylate for quantitative and on-site detection of PG via a smartphone-based sensing platform. The organogel-based assay detection limit was 1.0 µg mL-1 with recoveries ranging from 80.2% to 106.2% in edible oils and surface water. Suitability of the developed assay was also validated by high-performance liquid chromatography. Our study provides an effective fluorescent approach to rapid, specific, and convenient monitoring of PG, which is useful for diminishing the risk of PG exposure.

Effect of ethyl gallate and propyl gallate on dextran sulfate sodium (DSS)-induced ulcerative colitis in C57BL/6 J mice: preventive and protective.

OBJECTIVE AND DESIGN: Inflammatory bowel disease (IBD) is an idiopathic inflammatory condition of the digestive system marked by oxidative stress, leukocyte infiltration, and elevation of inflammatory mediators. In this study, we demonstrate the protective effect of ethyl gallate (EG), a phytochemical, and propyl gallate (PG), an anti-oxidant, given through normal drinking water (DW) and copper water (CW) in various combinations, which had a positive effect on the amelioration of DSS-induced ulcerative colitis in C57BL/6 J mice. MATERIALS AND METHODS: We successfully determined the levels of proinflammatory cytokines and anti-oxidant enzymes by ELISA, tracked oxidative/nitrosative stress (RO/NS) by in vivo imaging (IVIS) using L-012 chemiluminescent probe, disease activity index (DAI), and histopathological and morphometric analysis of colon in DSS-induced colitis in a model. RESULTS: The results revealed that oral administration of ethyl gallate and propyl gallate at a dose of 50 mg/kg considerably reduced the severity of colitis and improved both macroscopic and microscopic clinical symptoms. The level of proinflammatory cytokines (TNF-α, IL-6, IL-1ß, and IFN-γ) in colonic tissue was considerably reduced in the DSS + EG-treated and DSS + PG-treated groups, compared to the DSS alone-treated group. IVIS imaging of animals from the DSS + EG and DSS + PG-treated groups showed a highly significant decrease in RO/NS species relative to the DSS control group, with the exception of the DSS + PG/CW and DSS + EG + PG/CW-treated groups. We also observed lower levels of myeloperoxidase (MPO), nitric oxide (NO), and lipid peroxidation (LPO), and restored levels of GST and superoxide dismutase (SOD) in DSS + EG-DW/CW, DSS + PG/DW, and DSS + EG + PG/DW groups compared to DSS alone-treated group. In addition, we showed that the EG, PG, and EG + PG treatment significantly reduced the DAI score, and counteracted the body weight loss and colon shortening in mice compared to DSS alone-treated group. In this 21-day study, mice were treated daily with test substances and were challenged to DSS from day-8 to 14. CONCLUSION: Our study highlights the protective effect of ethyl gallate and propyl gallate in various combinations which, in pre-clinical animals, serve as an anti-inflammatory drug against the severe form of colitis, indicating its potential for the treatment of IBD in humans. In addition, propyl gallate was investigated for the first time in this study for its anti-colitogenic effect with normal drinking water and reduced effect with copper water.

Pharmacokinetic and toxicological overview of propyl gallate food additive.

The progressive use of food additives in "ultra-processed" food has increased attention to them. Propyl gallate (PG) is an essential synthetic preservative that commonly used in food, cosmetics, and pharmacies as an antioxidant. This study aimed to outline the existing evidence on the toxicological studies of PG including its physicochemical properties, metabolism, and pharmacokinetics effects. The methods include updated searches for the relevant databases. The EFSA has evaluated the use of PG in food industry. It establishes an acceptable daily intake (ADI) of 0.5 mg/kg bw per day. Based on exposure assessment, it can be concluded that at the current level of use, PG is not of safety concern.

High-dose synthetic phenolic antioxidant propyl gallate impairs mouse oocyte meiotic maturation through inducing mitochondrial dysfunction and DNA damage.

Propyl gallate (PG) is one of the most widely used antioxidants in food products, cosmetics and pharmaceutical industries. Increased research has suggested that exposure to PG influences reproductive health in humans and animals. However, until now, it has not yet been confirmed whether PG would impact oocyte quality. In this study, the hazardous effects of PG on oocyte meiotic maturation were investigated in mice. The findings showed that PG exposure compromises oocyte meiosis by inducing mitochondrial stress which activates apoptosis to trigger oocyte demise. Moreover, DNA damage was significantly induced in PG-treated oocytes, which might be another cause of oocyte developmental arrest and degeneration. Besides, the level of histone methylation (H3K27me2 and H3K27me3) in oocyte was also significantly increased by PG exposure. Furthermore, PG-induced oxidative stress was validated by the increased level of reactive oxygen species (ROS), which might be the underlying reason for these abnormities. In conclusion, the foregoing findings suggested that PG exposure impaired oocyte meiotic maturation by yielding mitochondrial stress to activate apoptosis, inducing DNA damage and oxidative stress, and altering histone methylation level.

Enhancing the stability of lutein emulsions with a water-soluble antioxidant and a oil-soluble antioxidant.

Lutein is critical for protecting the eye against light damage. The low solubility and high sensitivity of lutein to environmental stresses prevent its further application. The hypothesis is that the combination of one water-soluble antioxidant and one oil-soluble antioxidant will be beneficial to improve the stability of lutein emulsions. A low-energy method was performed to prepare lutein emulsions. The combination of a lipid-soluble antioxidant (propyl gallate or ethylenediaminetetraacetic acid) and a water-soluble antioxidant (tea polyphenol or ascobic acid) were investigated for improving the lutein retention rates. It was shown that the highest lutein retention rate was achieved by using propyl gallate and tea polyphenol, 92.57%, at Day 7. It was proven that the lutein retention rates of emulsions with propyl gallate and tea polyphenol were 89.8%, 73.5% and 55.2% at 4 °C, 25 °C and 37 °C, respectively, at Day 28. The current study is helpful to prepare for the further application of lutein emulsions for ocular delivery.

Boric acid group-functional Tb-MOF as a fluorescent and captured probe for the highly sensitive and selective determination of propyl gallate in edible oils.

This study reports the development of a Tb-metal-organic framework (Tb-MOF)-based fluorescent platform for the detection of propyl gallate (PG). The Tb-MOF using 5-boronoisophthalic acid (5-bop) as the ligand exhibited multiple emissions at 490, 543, 585, and 622 nm under an excitation wavelength of 256 nm. The fluorescence of Tb-MOF was selectively and significantly weakened in the presence of PG due to the special nucleophilic reaction between the boric acid of Tb-MOF and o-diphenol hydroxyl of PG, and the combined effect of static quenching and internal filtering. Furthermore, this sensor enabled the determination of PG within seconds in a wide linear range of 1-150 µg/mL, and with a low detection limit of 0.098 µg/mL, and high specificity against other phenolic antioxidants. This work provided a new route for the sensitive and selective determination of PG in soybean oil, thus was perspective to monitor and reduce the risk of PG overuse.

Effects of tetrasodium pyrophosphate coupled with soy protein isolate on the emulsion gel properties of oxidative myofibrillar protein.

The effects of protein oxidation on the emulsion gel properties of myofibrillar protein (MP) in the presence of tetrasodium pyrophosphate (TSPP) and soybean protein isolate (SPI) were investigated from the perspective of interfacial protein interactions. The results showed that the emulsifying activity and emulsion stability of MP increased by 35.2 %-181.6 % with elevated H2O2 concentrations (1-20 mM), while the gel strength and water holding capacity of MP emulsions first increased to a maximum at 5 mM H2O2 and then decreased. TSPP and SPI further reinforced the effects caused by oxidation. The emulsifying properties of MP and its emulsion gel properties were closely related to surface hydrophobicity/hydrogen bonds/hydrophobic interactions and disulfide bonds among interfacial proteins, respectively. However, these correlations became difficult to define when TSPP and SPI were introduced. The study provides a theoretical basis for the strategy development to reduce protein oxidation damage on meat product quality.

Isopropyl Gallate, a Gallic Acid Derivative: In Silico and In Vitro Investigation of Its Effects on Leishmania major.

Isopropyl gallate (IPG) is a polyphenol obtained from alterations in the gallic acid molecule via acid catalysis with previously reported leishmanicidal and trypanocidal activities. The present study aims to evaluate in silico binding activity towards some targets for antileishmanial chemotherapy against Leishmania major species, and ADMET parameters for IPG, as well as in vitro antileishmanial and cytotoxic effects. Molecular docking was performed using AutoDockVina and BIOVIA Discovery Studio software, whereas in silico analysis used SwissADME, PreADMET and admetSAR software. In vitro antileishmanial activity on promastigotes and amastigotes of Leishmania major, cytotoxicity and macrophages activation were assessed. IPG exhibited affinity for pteridine reductase (PTR1; -8.2 kcal/mol) and oligopeptidase B (OPB; -8.0 kcal/mol) enzymes. ADMET assays demonstrated good lipophilicity, oral bioavailability, and skin permeability, as well as non-mutagenic, non-carcinogenic properties and low risk of cardiac toxicity for IPG. Moreover, IPG inhibited the in vitro growth of promastigotes (IC50 = 90.813 µM), presented significant activity against amastigotes (IC50 = 13.45 µM), promoted low cytotoxicity in macrophages (CC50 = 1260 µM), and increased phagocytic capacity. These results suggest IPG is more selectively toxic to the parasite than to mammalian cells. IPG demonstrated acceptable in silico pharmacokinetics parameters, and reduced infection and infectivity in parasitized macrophages, possibly involving macrophage activation pathways and inhibition of leishmania enzymes.

A pharmacodynamic investigation to assess the synergism of orbifloxacin and propyl gallate against Escherichia coli.

Escherichia coli (E. coli) infections are becoming increasingly difficult to treat, as antibiotic-resistant variants proliferate. Studies on novel methods to combat the spread of resistance and improve the performance of current antibiotics are vital. We aimed to boost the efficacy of the antibiotic orbifloxacin (ORB) against E. coli by combining it with a phenolic component, propyl gallate (PG). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of ORB against the E. coli KVCC 1423 resistant strain were 128 µg/ml and 256 µg/ml, respectively. However, the MIC of ORB for the remaining E. coli strains was 0.5 µg/ml-2 µg/ml. For the combination of PG and ORB, the lowest fractional inhibitory concentration (FIC) index was less than 0.5, and the combination decreased the MIC of both drugs by 74%. The time-kill assay revealed the killing properties of both the drugs and the pharmacodynamic model (PD model) confirmed the strong killing properties of the combination as compared to the individual activities of the drugs. The ratio between MIC and mutant prevention concentration of ORB against E. coli 1400306 and 1,423 were 1:32 and 1:8, respectively. The combination of ORB and PG showed strong biofilm eradication and inhibited the motility of bacteria. The cell viability of the combination was > 80%. Therefore, we believe that ORB and PG in combination could be a possible antibacterial candidate that could minimize resistance and improve antibiotic potential.

The Anti-Apoptotic Effects of Caspase Inhibitors in Propyl Gallate-Treated Lung Cancer Cells Are Related to Changes in Reactive Oxygen Species and Glutathione Levels.

Propyl gallate [3,4,5-trihydroxybenzoic acid propyl ester; PG] exhibits an anti-growth effect in various cells. In this study, the anti-apoptotic effects of various caspase inhibitors were evaluated in PG-treated Calu-6 and A549 lung cancer cells in relation to reactive oxygen species (ROS) and glutathione (GSH) levels. Treatment with 800 µM PG inhibited the proliferation and induced the cell death of both Calu-6 and A549 cells at 24 h. Each inhibitor of pan-caspase, caspase-3, caspase-8, and caspase-9 reduced the number of dead and sub-G1 cells in both PG-treated cells at 24 h. PG increased ROS levels, including O2∙-, in both lung cancer cell lines at 24 h. Generally, caspase inhibitors appeared to decrease ROS levels in PG-treated lung cancer cells at 24 h and somewhat reduced O2∙- levels. PG augmented the number of GSH-depleted Calu-6 and A549 cells at 24 h. Caspase inhibitors did not affect the level of GSH depletion in PG-treated A549 cells but differently and partially altered the depletion level in PG-treated Calu-6 cells. In conclusion, PG exhibits an anti-proliferative effect in Calu-6 and A549 lung cancer cells and induced their cell death. PG-induced lung cancer death was accompanied by increases in ROS levels and GSH depletion. Therefore, the anti-apoptotic effects of caspase inhibitors were, at least in part, related to changes in ROS and GSH levels.

Investigation of the Antioxidant Properties of the Quaternized Chitosan Modified with a Gallic Acid Residue Using Peroxidase that Produces Reactive Oxygen Species.

Chitosan modified with a (2-hydroxy-3-trimethylammonium) propyl group and gallic acid residue, or quaternized chitosan with gallic acid (QCG), was synthesized. Antioxidant properties of the produced QCG have been investigated. Peroxidase in combination with NADH and salicyl hydroxamate (SHAM) caused consumption of oxygen and production of H2O2 in aqueous solution as a result of O2 reduction in the peroxidase-oxidase reactions. The rates of O2 consumption and H2O2 generation were reduced in the presence of QCG. The antioxidant propyl gallate (PG) and superoxide dismutase (SOD) had the same effect, but not the quaternized chitosan (QC) without gallic acid. The effect of chitosan derivatives on the production of reactive oxygen species (ROS) in the cells of pea leaf epidermis and on the cell death detected by the destruction of cell nuclei, was investigated. QCG, QC, and SOD had no effect, while PG decreased the rate of ROS generation in the cells of the epidermis, which was induced by NADH with SHAM or by menadione. QCG and QC prevented destruction of the guard cell nuclei in the pea leaf epidermis that was caused by NADH with SHAM or by KCN. SOD had no effect on the destruction of nuclei, while the effect of PG depended on the inducer of the cell death. Suppression of the destruction of guard cell nuclei by chitosan derivatives was associated not with their antioxidant effect, but with the disruption of the plasma membrane of the cells. The results obtained have shown that QCG exhibits antioxidant properties in solutions, but does not prevent generation of ROS in the plant cells. The mechanism of antioxidant effect of QCG is similar to that of PG and SOD.

Hemin loaded Zn-N-C single-atom nanozymes for assay of propyl gallate and formaldehyde in food samples.

Single-atom nanozymes (SAzymes) show distinct advantages in catalytic activity and selectivity owing to their stability and special characteristic of maximum atomic utilization. Inspired by the structure of natural horseradish peroxidase (HRP), we developed a simple method for specific determination of both propyl gallate (PG) and formaldehyde (HCHO) by utilizing the intrinsic peroxidase mimics activity of hemin (hem) loaded Zn-nitrogen-carbon single-atom nanozymes (Zn-N-C@hem SAzymes). Zn-N-C@hem was prepared via a salt-template strategy and self-assembly, where hemin exhibits enhancing peroxidase-like activity can catalyze oxidation of colorless PG to yellow product. Upon introduction of HCHO into Zn-N-C@hem/PG system, complete suppression of PG oxidation was showed, resulting in distinguished decrease in absorbance. The colorimetric sensors of PG and HCHO based on Zn-N-C@hem/PG were developed at their respective linear range of concentration 1.25-200 mg/kg and 5-250 mg/kg. The practicability of the rapid analysis of PG and HCHO in food samples has been verified with reliable results.

Synchronously activated strontium aluminate nanoflakes anchored functionalized carbon nanofiber nanocomposite for sensitive amperometric detection of food additive: Propyl gallate.

The contemporary dietary pattern is ruined by taste enhancers, flavoring agents, and preservatives. Propyl gallate (PG) is an imperative phenolic antioxidant cast-off to inhibit the oxidative mutilation in foodstuffs thereby preventing rancidity. Determination and annihilation of PG are extensively concerned because of its probable lethal effects on human well-being. Herein, we report an electrochemical sensor using SrAl2O4/f-CNF nanocomposite as an efficient electrode modifier with peculiar synergistic quantum confinement effects supporting the formation of heterojunction to facilitate electron transportation between its counterparts. The structural, morphological, and crystalline features of SrAl2O4/f-CNF nanocomposite was thoroughly examined. The proposed sensor possesses a wide linear range (0.1-1104.75 µM) with a remarkably low limit of detection (0.075 µM) and sensitivity (1.142 µA⋅µM-1⋅cm-2) measured at 0.2 V (vs. Ag/AgCl). The reliability of this sensor was evidenced through real-time monitoring of PG in edible oil which is beneficial for food quality monitoring and dropping the danger of abuse of PG in foods.

Cu3(PO4)2/BiVO4 photoelectrochemical sensor for sensitive and selective determination of synthetic antioxidant propyl gallate.

Propyl gallate (PG) as one of the most important additives has been widely used to prevent or slow the oxidation of foods in the food industry. In this work, Cu3(PO4)2/BiVO4 composite is synthesized through two hydrothermal processes. With visible light irradiation, the Cu3(PO4)2/BiVO4 composites modified PEC platform displays a superior anode photocurrent signal. The PEC sensor showed a wide linear range from 1 × 10-10 to 1 × 10-3 mol L-1 with a detection limit as low as 0.05 × 10-10 mol L-1. The Cu3(PO4)2/BiVO4 photoelectrochemical (PEC) sensor is designed and characterized by electrochemical impedance. Compared with GCE/BiVO4 and GCE/Cu3(PO4)2, the GCE/Cu3(PO4)2/BiVO4 has a higher photocurrent response. In addition, the sensor is highly selective for samples containing other antioxidants. Furthermore, the sensor can be used to detect PG in edible oil samples with satisfactory results. The recoveries of propyl gallate in edible oil ranged from 95.5 to 101.8%. The results show that Cu3(PO4)2/BiVO4 composites can be used to analyze PG in different edible oil samples, which are beneficial for food quality monitoring and reduce the risk of PG overuse in food.

Development of Lomustine and n-Propyl Gallate Co-Encapsulated Liposomes for Targeting Glioblastoma Multiforme via Intranasal Administration.

This work aimed to develop lomustine (LOM) and n-propyl gallate (PG)-loaded liposomes suitable for targeting glioblastoma multiforme (GBM) via the auspicious nose-to-brain drug delivery pathway. The therapeutical effect of LOM, as a nitrosourea compound, can be potentiated by PG suitable for enhanced anti-cancer therapy. Nose-to-brain delivery of PG and LOM combined in liposomes can overcome the poor water solubility, absorption properties, and toxicity issues in the systemic circulation. Optimization and characterization of the liposomal carrier with binary drug contents were carried out in order to achieve adequate encapsulation efficiency, loading capacity, drug release, and ex vivo permeation. The optimized liposome co-encapsulated with both drugs showed suitable Z-average (127 ± 6.9 nm), size distribution (polydispersity index of 0.142 ± 0.009), zeta potential (-34 ± 1.7 mV), and high encapsulation efficacy (63.57 ± 1.3% of PG and 73.45 ± 2.2% of LOM, respectively) meeting the acceptance criteria of nose-to-brain transport for both drugs. MTT assays of PG-LOM formulations were also conducted on NIH/3T3 (murine embryonic fibroblast), U87 (glioblastoma), and A2780 (ovarian cancer) cell lines indicating reduced an antiproliferative effect on all types of cells. Our results supported the use of this novel combination of LOM and PG in a liposomal formulation as a promising carrier for glioblastoma targeting via the intranasal route.