Diabetes mellitus (DM) continues to be a significant worldwide health problem, with restrictions on existing treatment options because of the poor bioavailability of many active compounds and their adverse effects. Harmine (HRM), a beta-carboline alkaloid with antidiabetic and antioxidant properties, has low aqueous solubility and limited oral absorption, which restricts its clinical potential. Our study aimed to develop harmine (HRM)-containing NE formulation (HRM-NE) to overcome these limitations and characterize it in vitro (TEM image, zeta potential, pH measurement, entrapment efficiency, droplet size, size distribution, and in vitro release) and in vivo (hypoglycemic effect, antioxidant effect, and liver tissue's histological evaluation). The HRM-NE formulation had a droplet size of around 200 nm with PDI<0.3 (a narrow size distribution), and a suitable zeta potential value (-38.67 mV) for acceptable physical stability. Its pH value was around 4. The % entrapment efficiency value for the HRM-NE formulation was 98.23 +/- 0.87%. The blood glucose levels of diabetic rats in the groups treated with pure HRM (5, 10, and 15 mg/kg) or HRM-NE (5, 10, and 15 mg/kg HRM equivalent) administered diminished significantly over time (p < 0.05). On the 21(st) day of the application, the blood glucose level of diabetic rats in the D-HRM-NE 15 group was significantly less than that of diabetic rats in the D-HRM 15 group (p < 0.05). Compared with the DC group (diabetic control), liver SOD activity and GSH levels of diabetic rats administered HRM or HRM-NE (for all doses) were significantly increased, and blood glucose, liver MDA and serum AST and ALT levels were reduced significantly (p < 0.05). In particular, the D-HRM-NE 15 group caused a noticeable decrease in oxidative stress markers and marked improvement in diabetic rats' liver tissues. The results indicate that NE formulation is a potential delivery system for the oral administration of HRM.

Spironolactone (SPL) is a mineralocorticoid receptor antagonist widely used in the management of hypertension and heart failure; however, its poor aqueous solubility and variable oral bioavailability limit its therapeutic performance. This study aimed not only to enhance the solubility and dissolution behavior of SPL through Hp-βCD complexation, but also to translate this approach into a scalable tablet dosage form and evaluate its in vitro and in vivo performance. An Hp-βCD: SPL inclusion complex (1:1 molar ratio) was prepared using the kneading method. The solid-state characteristics and complex formation were evaluated by Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). Solubility studies were conducted in acidic medium (0.1 N HCl, pH 1.2, 0.1

Background and Aims: This study aimed to prepare and characterize (in vitro) nanoemulsion (NE) and NE-based gel (NEG) formulations containing fluconazole (FLU) and daidzein (DZ) alone or in combination for topical application on the skin or vaginal administration.Methods: The HPLC-UV method for simultaneously determining FLU and DZ was also developed and validated. We prepared the NE formulations using high-speed mixing and ultrasonication techniques. Then, gel formulations were prepared using sodium carboxymethyl cellulose (1%; NaCMC) as a gelling agent. In vitro characterization studies (the determination of zeta potential, droplet size, and PDI values for NE formulations, pH and viscosity measurements, FTIR analysis, and in vitro release studies) were performed on these formulations.Results: The prepared NE formulations’ droplet sizes were smaller than 120 nm, and the PDI values were smaller than 0.3. In addition, the zeta potential values for NE formulations were sufficient for physical stability. High EE% values (over 95% for both FLU and DZ) were obtained for NE and NEG formulations containing FLU and/or DZ. While the NE formulations showed Newtonian behavior, the NEG formulations showed pseudoplastic behavior.Conclusion: NE and NEG formulations were successfully prepared and in vitro characterized in our study.

Acemetacin (ACIN) is a poorly water-soluble nonsteroidal anti-inflammatory drug, which limits its effectiveness in topical therapeutic applications. This study aimed to enhance the delivery potential and dermal applicability of ACIN through the development of bilosome-loaded hydrogel formulations. Bilosomes were prepared using the thin-film hydration method and optimized using Box-Behnken Design (BBD). The amount of phosphotidylcholine (lecithin), cholesterol and sodium taurocholate were chosen as the formulation parameters and their effects were evaluated on the resulting vesicle size, zeta potential and entrapemnet efficiency percentage (EE

Objective: Artemisia dracunculus is a plant traditionally used in folk medicine, and its antioxidant, anti-inflammatory, and antihyperglycemic effects have been demonstrated in scientific studies. This study aims to prepare alginate beads containing the aqueous extract of Artemisia dracunculus and perform in vitro characterization studies.Methods: Four different extraction methods were tested to prepare the water extract, and the total phenolic content of the extracts was determined using the Folin–Ciocalteu method. The extract with the highest phenolic content was selected, and alginate beads were prepared by ionotropic gelation. The beads were dried using oven-drying or lyophilization methods. The beads were characterized in vitro (particle size, morphological analysis, encapsulation efficiency, swelling behavior, and FT-IR analyses). Results: The bead sizes were found to range from 0.73 ± 0.12 mm to 1.76 ± 0.13 mm, and it was determined that lyophilized beads were larger and more porous. The entrapment efficiency was found to range from 4.86% to 14.28%. Swelling studies have shown that lyophilized beads have a higher swelling capacity. FT-IR analysis revealed that the extracts were retained within the polymer matrix.Conclusion: Alginate beads containing Artemisia dracunculus aqueous extract have been successfully prepared and characterized in vitro.

Objective: We aimed to prepare the ethanol extract (Hp-Et) of the aerial parts of Heracleum persicum (Hp) and to determine its antioxidant capacity. We also aimed to develop nanoemulsion (NE) and NE-based gel (NEG) formulations containing this extract for topical application to the skin for wound healing and to characterize these formulations in vitro.Methods: After the preparation of Hp-Et, its antioxidant capacity was determined by FRAP, CUPRAC, and DPPH methods. Then, blank NE (B-NE) and the extract-containing NE (Hp-Et-NE) formulations were developed and in vitro characterized [morphological analysis; centrifuge test; the determination of droplet size (DtS), polydispersity index (PDI) and zeta potential; viscosity and pH measurements; FT-IR analysis]. Additionally, B-NEG and Hp-Et-NEG were prepared and in vitro characterized [viscosity and pH measurements; FT-IR analysis].Results: DtS and zeta potential values of NE formulations were around 200 nm and -30 mV, respectively. PDI values were less than 0.4. The pH values for NE and NEG formulations were in the range of 4.63±0.01-5.73±0.01. The NE and NEG formulations showed Newtonian and pseudoplastic behaviors, respectively.Conclusion: Hp-Et-NEG exhibits the desired pseudoplastic behavior for topical application to the skin.

Diabetes mellitus (DM) continues to be a significant worldwide health problem, with restrictions on existing treatment options because of the poor bioavailability of many active compounds and their adverse effects. Harmine (HRM), a β-carboline alkaloid with antidiabetic and antioxidant properties, has low aqueous solubility and limited oral absorption, which restricts its clinical potential. Our study aimed to develop harmine (HRM)-containing NE formulation (HRM-NE) to overcome these limitations and characterize it in vitro (TEM image, zeta potential, pH measurement, entrapment efficiency, droplet size, size distribution, and in vitro release) and in vivo (hypoglycemic effect, antioxidant effect, and liver tissue’s histological evaluation). The HRM-NE formulation had a droplet size of around 200 nm with PDI<0.3 (a narrow size distribution), and a suitable zeta potential value (-38.67 mV) for acceptable physical stability. Its pH value was around 4. The % entrapment efficiency value for the HRM-NE formulation was 98.23±0.87%. The blood glucose levels of diabetic rats in the groups treated with pure HRM (5, 10, and 15 mg/kg) or HRM-NE (5, 10, and 15 mg/kg HRM equivalent) administered diminished significantly over time (p<0.05). On the 21st day of the application, the blood glucose level of diabetic rats in the D-HRM-NE 15 group was significantly less than that of diabetic rats in the D-HRM 15 group (p<0.05). Compared with the DC group (diabetic control), liver SOD activity and GSH levels of diabetic rats administered HRM or HRM-NE (for all doses) were significantly increased, and blood glucose, liver MDA and serum AST and ALT levels were reduced significantly (p<0.05). In particular, the D-HRM-NE 15 group caused a noticeable decrease in oxidative stress markers and marked improvement in diabetic rats' liver tissues. The results indicate that NE formulation is a potential delivery system for the oral administration of HRM.

Epilepsy, the most common neurological disorder worldwide, is characterized by sudden paroxysmal brain activity, which can be generalized or focal. Extensive research has explored various treatment strategies for this condition. Our study used a pilocarpine (PL)-induced seizure model in zebrafish (Danio rerio) embryos and larvae to assess the effects of carbamazepine (CBZ)-loaded chitosan-coated PLGA-Zein nanoparticles (NPs) over 96 hr. We evaluated the developmental toxicity (mortality, malformation, and larval hatching), behavioral changes (sensorimotor reflexes), and histopathological and immunohistochemical alterations in brain tissue, focusing on 5-hydroxytryptamine receptor 4 (5HT4), and brain and muscle ARNT-like 1 (BMAL1) expressions. Our findings revealed high mortality and malformation rates in groups treated with pure CBZ (PL + CBZ 50 and PL + CBZ 100). These groups also exhibited delayed hatching and impaired sensorimotor reflexes. In contrast, the CBZ-NP-treated groups (PL + CBZ NP 50 and PL + CBZ NP 100) showed hatching rates comparable with the control group, with significantly lower mortality and malformation rates compared with pure CBZ-treated groups. Moreover, intense cytoplasmic expression of 5HT4 and BMAL1 was observed in neuropils of the PL + CBZ 100 group. This study highlights the potential of CBZ-loaded NPs in reducing developmental toxicity and adverse neurological effects associated with pure CBZ treatment in seizure models.

Dittrichia viscosa (L.) Greuter (Dv) has antimicrobial, analgesic, antioxidant, anti-inflammatory, cytotoxic, and wound-healing properties. We aimed to prepare the methanol extract (Dv-Me) of the aerial parts of Dv and to determine its antioxidant capacity by FRAP, CUPRAC, and DPPH methods. In addition, we prepared nanoemulsion (NE) and NE-based gel (NEG) formulations containing Dv-Me for topical application to the skin for wound healing and characterized these formulations in vitro. The antioxidant capacity of Dv-Me was determined by CUPRAC, FRAP, and DPPH methods. Then, NE formulations with/without extract (B-NE and Dv-Me-NE) were developed and in vitro characterized [morphological analysis; centrifuge test; viscosity and pH measurements; FT-IR analysis; the determination of zeta potential, droplet size and polydispersity index (PDI)]. Besides, B-NEG and Dv-Me-NEG were prepared and in vitro characterized [FT-IR analysis; viscosity and pH measurements]. The droplet size and zeta potential values of NE formulations were smaller than 185 nm and around -30 mV, respectively. PDI values were found to be less than 0.3. The pH values of Dv-Me-NE and Dv-Me-NEG were found to be 5.13±0.01 and 5.87±0.02, respectively. The NE and NEG formulations showed Newtonian and pseudoplastic behaviors, respectively. As a result, Dv-Me-NEG exhibits the desired pseudoplastic behavior for topical application to the skin.

Desloratadine (DL) and montelukast sodium (MTS) are combined in a pharmaceutical preparation for the treatment of allergic rhinitis and asthma. DL is a competitive H1-receptor antagonist and helps the management of allergic reactions and relieves allergy symptoms, while MTS is a leukotriene receptor antagonist that inhibits the effects of inflammatory mediators. This study introduces a machine learning-assisted UV-Vis spectrophotometric method for the simultaneous quantification of DL and MTS in a commercial film-coated tablet, addressing limitations due to spectral overlap. Five machine learning regression models (Support Vector Regression, Ridge Regression, Lasso Regression, Elastic Net, and Linear Regression) were evaluated. Ridge Regression (λ = 0.1) was selected for its balance of accuracy, computational efficiency, and robustness. The method was applied using Aircomb ® film-coated tablets, containing 5 mg DL and 10.4 mg MTS, ensuring high precision. The developed method demonstrated high recovery rates (99.25% for DL and 101.0% for MTS with minimal relative standard deviation (≤ 1.59%). Sustainability assessments using Analytical GREEnness Metric (AGREE) and Complex Green Analytical Procedure Index (ComplexGAPI) confirmed its alignment with green analytical chemistry principles. Ridge Regression (λ = 0.1) provided accurate and reproducible results, making it suitable for routine pharmaceutical analysis. This study highlights the potential of machine learning-assisted UV-Vis spectrophotometry as a cost-effective and environmentally friendly alternative for pharmaceutical quality control. The method minimizes solvent consumption while ensuring analytical precision. Future research may explore non-linear models, such as artificial neural networks, to enhance predictive performance and broaden its applicability.

Centaurea depressa M. Bieb. is used in traditional medicine as wound healing, antidiabetic, antibacterial, antimalarial, antirheumatic, diuretic, antipyretic, antibacterial, tonic, astringent, choleretic. It is popularly used as poultice, pounded, infusion, decoction, external, and internal. This study aimed to develop and in vitro characterize the methanol extract of Centaurea depressa (MCD)-containing nanoemulsion formulation (MCD-NEF) to heal the wound effectively and analyze the phenolic compounds. MCD-NEF was prepared and its droplet size, PDI, and ZP, and viscosity were determined. The effect of MCD and MCD-NEF on human dermal fibroblast cell viability was examined by MTT assay. MCD's phenolic compound profiles were analyzed by LC-MS/MS. Also, MCD and MCD-NEF's wound healing potential was evaluated using the scratch assay. The droplet size, PDI, ZP, pH and viscosity values for the MCD-NEF were found to be 152.42 +/- 3.50 nm, 0.187 +/- 0.020, (-)27.67 +/- 1.68 mV, 5.57 +/- 0.03, and 1.891 +/- 0.010 cP, respectively. In the cell viability assay, the highest percentage of living cells was obtained at concentration of 16 mu g/mL for the MCD and MCD-NEF. In the scratch assay, MCD-NEF showed significantly ameliorated wound closure % rates at 24 and 30 h than the control, MCD and blank-NEF (without MCD) groups (p < 0.001). In this study, immunofluorescence staining was carried out. TGF-beta 1 and FGFR-2 expressions in MCD-NEF-treated fibroblast cells increased significantly at 24 and 30 h compared to the control, MCD, and B-NEF groups (p < 0.001). MCD's. Twenty-seven phenolic compounds, including quinic acid, chlorogenic acid, cynaroside, cosmosiin, protocatechuic acid and isoquercitrin were determined by LC-MS/MS to be major phytochemical compounds in MCD. Our findings show that MCD-NEF may be promising for better wound healing.

The aim of this study is to prepare CBZ-loaded chitosan (Ch)- coated/uncoated poly(lactic-co-glycolic acid) (PLGA) and Zein (using 20 mg or 40 mg Zein) nanoparticles (CBZ-PLGA-Zein-NPs or CBZ-PLGA-Zein-Ch-NPs) and to characterize (Particle size, PDI, zeta potential, percent encapsulation efficiency (EE%), FT-IR, DSC and XRD analyzes, and in vitro release study) them in vitro. These nanoparticles were prepared using a modified emulsification-solvent evaporation method. The particle sizes of CBZ-PLGA-Zein(20)-NPs, CBZ-PLGA-Zein(40)-NPs and CBZ-PLGA-Zein(20)-Ch-NPs were found to be about 222 nm, 245 nm and 221 nm, respectively. The PDI value of all NP formulations was below 0.3. This indicates a narrow particle size distribution. The EE% values of CBZ-PLGA-Zein(20)-NPs, CBZ-PLGA-Zein(40)-NPs and CBZ-PLGA-Zein(20)-Ch-NPs were determined as about 64%, 56% and 62%, respectively. The coating of the optimum formulation (containing 20 mg Zein) with chitosan did not lead to a significant difference in the particle size and EE% value of this formulation (P>0.05). A sustained release of CBZ from all prepared NPs formulations was achieved until 48th h. In conclusion, CBZ-PLGA-Zein(20 mg or 40 mg)-NPs and CBZ-PLGA-Zein(20 mg)-Ch-NPs were successfully prepared and characterized in vitro.

Herein we report the feasibility of pectin vitex essential oil (VEO) nanoemulsions (NE). NE formulations were prepared both in the absence and presence of a conventional surfactant (Tween 80) by ultrasonication using pectin aqueous solutions as the aqueous phase and VEO as the oil phase. Different surfactant amounts and various ultrasonication times were employed. Droplet size and Zeta potential measurements were performed and their data were statistically evaluated. The minimum droplet size (prediction: 299.342 nm) could be achieved when employing an ultrasonication time of 5.9 min in the absence of the conventional surfactant. SEM characterization delivered supporting results related to the droplet sizes obtained. Stability tests showed that pectin VEO NE formulations were stable after 42 days. The results clearly showed that it was possible to generate VEO containing NEs in one pot and at once using pectin, which also acted as a natural surfactant, without the need for an additional conventional surfactant. Considering also moisturizing property of pectin and the antifungal activity of VEO, their combination in the form of a nanoemulsion could be promising for potential women's health applications.

Repaglinide (RPG) belongs to the class of drugs known as meglitinides and is used for improving and maintaining glycemic control in the treatment of patients with Type 2 diabetes. RPG is a Class II drug (BCS) because of its high permeability and low water solubility. It also undergoes hepatic first-pass metabolism. The oral bioavailability of RPG is low (about 56 %) due to these drawbacks. Our aim in this study is to prepare two different nano-sized drug carrier systems containing RPG (nanoparticle: RPG-PLGA-Zein-NPs or nanoemulsion: RPG-NE) and to carry out a pharmacokinetic study for these formulations. We prepared NPs using PLGA and Zein. In addition, a single NE formulation was developed using Tween 80 and Pluronic F68 as surfactants and Labrasol as co-surfactant. The droplet size values of the blank-NE and RPG-NE formulations were found to be less than 120 nm. The mean particle sizes of blank-Zein-PLGA-NPs and RPG-Zein-PLGA-NPs were less than 260 nm. The Cmax and tmax values of RPG-Zein-PLGA-NPs and RPG-NE (523 ± 65 ng/mL and 770 ± 91 ng/mL; 1.41 ± 0.46 h and 1.61 ± 0.37 h, respectively) were meaningfully higher than those of free RPG (280 ± 33 ng/mL; 0.72 ± 0.28 h) (p < 0.05). The AUC0-∞ values calculated for RPG-Zein-PLGA-NPs and RPG-NE were approximately 4.04 and 5.05 times higher than that calculated for free RPG. These nanosized drug delivery systems were useful in increasing the oral bioavailability of RPG. Moreover, the NE formulation was more effective than the NP formulation in improving the oral bioavailability of RPG (p < 0.05).

Colorectal cancer is the third most common malignancy worldwide and the second most common cause of cancer deaths. Alternative treatment strategies, including nano-based formulations, show remarkable promise to improve the efficacy of chemotherapy. The soy isoflavone daidzein has attracted attention for its anti-cancer activity. The aim of this study was to investigate the effects of daidzein nanosuspension with 5-fluorouracil on apoptosis and inflammation induced in human colorectal adenocarcinoma cells (Caco-2). Cytotoxicity, total antioxidant/oxidant status (TAS, TOS), and the expression of proteins associated with apoptosis and inflammation were analyzed by the MTT, ELISA and qRT-PCR, respectively. Daidzein nanosuspension showed a strong cytotoxicity (IC 50 = 240.3 mu M for daidzein, IC 50 = 35.34 mu M for daidzein nanosuspension) compared to daidzein. The combination of 5-fluorouracil and daidzein nanosuspension treatment showed a synergistic antiproliferative effect without increasing oxidative stress. The combination showed a significant increase in p53 levels and a significant decrease in Bcl-2, IL-6, TNF- alpha and MMP-9 levels. qRT-PCR results showed that the combinations of daidzein and DZ-NS with 5-FU regulated these parameters in Caco-2 cells. In conclusion, daidzein nanosuspension with 5-fluorouracil treatment reduced the proliferation and inflammation and increased apoptosis of Caco-2 cells without oxidative stress. The current study shows that this combination also elucidates several signaling pathways, including effects on oxidative stress, apoptosis, and inflammation. The integration of this nanotechnology approach into traditional chemotherapy will form the basis of an innovative strategy.

It was aimed to develop and in vitro characterize the methanol extract of Hypericum linarioides (MHL)-containing nanoemulsion formulation (MHL-NEF) to heal the wound effectively. MHL-NEF was prepared and its droplet size, polydispersity index (PDI), viscosity, pH and zeta potential (ZP) values were determined. The effect of MHL and MHL-NEF on human dermal fibroblast cell viability was examined by MTT assay. Also, their wound healing potential was evaluated using the scratch assay. The droplet size, PDI, ZP, pH and viscosity values for the MHL-NEF were found to be 157.67±7.61 nm, 0.268±0.036, (-)40.20±6.79 mV, 4.27±0.01, and 1.82±0.01 cP, respectively. In the cell viability assay, the highest percentage of living cells was obtained at concentration of 0.4 µg/mL for the MHL and MHL-NEF. In the scratch assay, MHL-NEF showed significantly ameliorated wound closure (%) rates at 24 and 30 h than the groups of control, MHL and blank-NEF (NEF without MHL) (p < 0.001). Immunofluorescence staining was carried out. TGF-β1 and FGFR-2 expressions in MHL-NEF-treated fibroblast cells increased significantly at 24 h compared to the groups of control, MHL, and B-NEF (p < 0.001). Our findings show that MHL-NEF may be promising for better wound healing.

Microplastics have been detected in marine and terrestrial ecosystems, yet the toxic effects of microplastics on living organisms are poorly known. In particular, there is few knowledge on the relationship between microplastic exposure and human cancer. Here we studied the occurrence of microplastics in tumoral and non-tumoral colon tissues of patients diagnosed with colorectal adenocarcinoma, and in colon tissues of subjects not diagnosed with colorectal cancer, as control. Microplastics were analyzed by attenuated total reflection-Fourier-transform infrared and Raman spectroscopies. Results show that the number of microplastics in tumoral colon tissues is higher than the number of microplastics in non-tumoral colon tissues or control. The particle size of microplastics extracted from colon tissues ranges from 1 to 1299 μm. The microplastics included polyethylene, poly(methyl methacrylate), and Nylon (polyamide). Overall, our findings suggest a possible connection between colorectal cancer and microplastic exposure.

Background and Aims: Epilepsy is one of the most disabling and most common neurological disorders, affecting approximately 65 million people of all age groups worldwide. When there is no response to monotherapy in the treatment of epilepsy, the combined use of Carbamazepine (CARBA) and Levetiracetam (LEV), which have different mechanisms of action, can be additive/synergistic and may be useful in the clinic. The aim of our study is to develop a fixed-dose combination (FDC)-nanoemulsion (NE) formulation containing CARBA and LEV for the treatment of epilepsy.Methods: Blank NE (BLNK-NE) and CARBA+LEV-FDC-NE formulations were prepared and carried out the in vitro characterization studies [morphological analysis, centrifugation test, droplet size (DS), polydispersity index (PDI), zeta potential (ZP), viscosity and pH measurements, FT-IR analysis, the percent entrapment efficiency (EE%), and in vitro release study]. Results: The DS, PDI, pH, and ZP values for the BLNK-NE formulation were found to be 117.63 & PLUSMN;3.82 nm, 0.240 & PLUSMN;0.014, 4.62 & PLUSMN;0.03, and (-)26.07 & PLUSMN;3.04 mV, respectively. For the CARBA+LEV-FDC-NE formulation, the DS, PDI, pH, and ZP values were determined as 137.56 & PLUSMN;3.11 nm, 0.225 & PLUSMN;0.013, 4.60 & PLUSMN;0.06, and (-)21.62 & PLUSMN;0.29 mV, respectively. The EE% values obtained for CARBA+LEV-FDC-NE were 97.33 & PLUSMN;0.56% (for CARBA) and 96.73 & PLUSMN;0.91% (for LEV).Conclusion: The CARBA+LEV-FDC-NE formulation was successfully prepared. This formulation had suitable in vitro characterization results.

Lung cancer is the most common cause of cancer-related mortality, chemo-resistance, and toxicity limit treatment. The focus is on innovative combined phytotherapy to improve treatment outcomes. Our aim was to investigate the potential effects of daidzein nanosuspension (DZ-NS) and its combination with cisplatin (CIS) on A549 non-small lung cancer cells. Cytotoxicity was investigated using MTT and Chou-Talalay methods. Oxidative, apoptotic, and inflammatory markers were analyzed by ELISA and qRT-PCR. The IC50 value for DZ-NS was 25.23 µM for 24 h and was lower than pure DZ (IC50 = 835 µM for pure DZ). DZ-NS (at IC50x2 and IC50 values) showed synergistic cytotoxicity with CIS. The cells treated with DZ-NS had low TOS and OSI levels. However, DZ-NS failed to regulate Cas3 and TGF-β1 activation in A549 cells. MMP-9 gene expression was significantly suppressed in DZ-NS-treated cells, especially in combination therapy. DZ represents a potential combination option for the treatment of lung cancer, and its poor toxicokinetic properties limit its clinical use. To overcome these limitations, the effects of the nanosuspension formulation were tested. DZ-NS showed a cytotoxic effect on A549 cells and optimized the therapeutic effect of CIS. This in vitro synergistic effect was mediated by suppression of MMP-9 and not by oxidative stress or Cas3-activated apoptosis. This study provides the basis for an in vivo and clinical trial of DZ-NS with concurrent chemotherapy.