Vector control remains the main strategy to reduce Trypanosoma cruzi transmission, particularly in endemic areas where Rhodnius prolixus is a primary vector. However, the intensive use of pyrethroids has led to the emergence of resistant populations, highlighting the need for new insecticidal technologies. The present study evaluated the efficacy of a novel fipronil oily film formulation based on poly(vinyl alcohol) and a sunflower oil–Tween 80 vehicle. Formulations with one- and two-part oil contents were applied to glass and filter paper surfaces, and fifth-instar R. prolixus nymphs were exposed to four fipronil doses (0.4–4.0 g m⁻²). Mortality was recorded at 24, 48, and 72 h, and topical bioassays were performed to estimate lethal doses. All formulations produced stable films. While both formulations achieved 100
Breast cancer (BC) is the most frequently diagnosed malignancy in women and triple-negative breast cancer (TNBC) is its most aggressive subtype of BC, often associated with poor prognosis due to the limited current therapies. Effective delivery systems for metal-based drugs could improve antitumor efficacy and selectivity. In this study, the copper-complex [Cu(N-N-Fur)(NO3)(H2O)] (CuL1), which has demonstrated anticancer activity, was encapsulated into Eudragit®-based nanoparticles to enhance its effects against TNBC cell lines (MDA-MB-231, 4T1, and Hs 578T). Two nanosystems were prepared by nanoprecipitation followed by ultrasonication, using Eudragit® E100/S100 (ES-CuL1) or Eudragit® E100/NE100D (ENE-CuL1). The physicochemical and morphologic properties were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), fourier transformed infrared spectroscopy (FTIR), and small-angle X-ray scattering/wide-angle X-ray scattering (SAXS/WAXS). Both formulations showed encapsulation efficiencies of CuL1 above 90 % and in vitro controlled drug release over 72 h. Cytotoxicity and apoptosis were evaluated in 2D monolayers and 3D spheroids of TNBC. Notably, ES-CuL1 enhances the cytotoxic activity of CuL1, showing increased cytotoxicity across all 2D cell lines. Consistently, the encapsulated complex significantly reduced clonogenic survival from 0.5 µM onward and induced a higher proportion of late apoptotic cells in all tested lines. In 3D models, ES-CuL1 produced similar effects to the free drug in 4T1 spheroids but elicited a stronger cytotoxic response in Hs 578T spheroids, suggesting improved penetration and retention in tumor-like structures. The superior performance of ES-CuL1 supports its potential as effective nanocarrier for BC therapy and highlights the predictive value of 3D spheroids for nanodrug evaluation.
Drug controlled release systems are widely studied in the pharmaceutical and veterinary industry to improve therapies effectiveness. During the present investigation, in situ implants containing progesterone were prepared by using biodegradable poly (D,L-lactide-co-glycolic) polymer and phase inversion technique. N-methyl-2-pyrrolodone, glycerol formal and dimethyl sulfoxide were used as partially water-soluble solvents for the implant formulations. Encapsulation efficiencies, structural morphologies and mathematical modeling of in vitro release were studied. Concerning encapsulation efficiencies, all of them were higher than 60 %. Implants structures and porosities depended on the solvent and drug to polymer ratio. The proposed in vitro swelling-diffusive model showed the best adjustment for all the implants. In addition, two formulations were selected for dairy cows performance experiments. Results showed that progesterone concentrations could not be maintained over the basal plasma levels during >24-48 h. The in vivo mathematical modeling performance was probably affected by the in vitro-in vivo implants morphologic differences.
The liver, which plays pivotal roles in metabolism and immunity, often confers tolerance, suppressing immune responses to pathogens. Adjuvanted, lipid nanoparticle-encapsulated mRNA vaccines (mRNA-LNPs) offer a promising approach to overcome immune tolerance. In this study, the immunostimulatory activity of well-documented adjuvants, i.e., 2'3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), resiquimod (R848), and polyinosinic:polycytidylic acid (Poly I:C), on non-parenchymal liver cells was determined. When co-applied with mRNA-loaded LNPs, these adjuvants enhanced immune responses at variable extents. Moreover, the efficiency of mRNA translation in the presence of cGAMP was comparable with the non-adjuvanted control. Repetitive co-application of adjuvants with mRNA-LNPs showed improvement in cellular responses when R848 or R848/cGAMP treatments were used. These findings emphasize the need to delineate the delicate balance between immunomodulatory properties and the efficiency of mRNA translation when selecting adjuvants for mRNA-LNP vaccines and offer insights on how to enhance immunity to infectious diseases and cancers that affect the liver.
This study investigated the use of riboflavin-targeted Nanostructured Lipid Carriers (R-NLCs) to deliver a platinum-based anticancer drug [PtCl(8-O-quinolinate)(dmso)] (8-QO-Pt) to colorectal cancer cells. Three different R-8-QO-Pt-NLC formulations were prepared via hot-homogenization by ultrasonication method. The physicochemical characterizations of NLCs were analyzed by small- and wide-angle X-ray scattering (SAXS/WAXS) and fourier transformed infrared spectroscopy (FTIR). The cytotoxic effects and IC50 values of R-8-QO-Pt-NLC formulations were compared with those of the free 8-QO-Pt. Cellular uptake and apoptosis were evaluated towards HCT 116 cells in monolayer (2D). The liquid overlay technique was used to generate 3D multicellular tumor spheroids, MCTS. The anticancer and antimetastatic activities of the free 8-QO-Pt and R-8-QO-Pt-NLCs were determined in MCTS. The results revealed that R-8-QO-Pt-NLC exhibited greater cytotoxicity and lower IC50 values than free 8-QO-Pt in both 2D and 3D cell cultures. Furthermore, results showed that the volumes of the spheroids were reduced in response to increasing concentrations of R-8-QO-Pt-NLC, showing higher inhibition of cell migration in colorectal cancer spheroids at concentrations of 10.0, 15.0, and 25.0 μM than free 8-QO-Pt. To provide protection against gastric acid conditions, an additional drug delivery system based on alginate (Alg) and gelatin (Gel) beads for R-8-QO-Pt-NLC oral administration was developed. While free and R-NLC encapsulated 8-QO-Pt were practically inactivated at pH 1.2 and 37 °C, it was revealed that the Alg-Gel beads retain 5.7 times the initial activity of the R-8-QO-Pt-NLC. The findings of this research indicate that R-8-QO-Pt-NLC embedded in Alg-Gel beads are promising hydrogels for targeted colorectal delivery systems.
Background/Objectives: Drug repurposing explores new applications for approved medications, such as simvastatin (SV), a lipid-lowering drug that has shown anticancer potential but is limited by solubility and side effects. This study aims to enhance SV delivery and efficacy against lung cancer cells using bioactive lipid nanoparticles formulated with plant-derived monoterpenes as both nanostructuring agents and anticancer molecules. Methods: Lipid nanoparticles were produced by ultrasonication and characterized for morphology, size, zeta potential, and polydispersity index (PDI). Monoterpenes (linalool-LN-, limonene, 1,8-cineole) or Crodamol® were used as liquid lipids. Encapsulation efficiency (EE), release profiles, stability, biocompatibility, protein adsorption, cytotoxicity, and anticancer effects were evaluated. Results: The nanoparticles exhibited high stability, size: 94.2 ± 0.9–144.0 ± 2.6 nm, PDI < 0.3, and zeta potential: −4.5 ± 0.7 to −16.3 ± 0.8 mV. Encapsulation of SV in all formulations enhanced cytotoxicity against A549 lung cancer cells, with NLC/LN/SV showing the highest activity and being chosen for further investigation. Sustained SV release over 72 h and EE > 95% was observed for NLC/LN/SV. SAXS/WAXS analysis revealed that LN altered the crystallographic structure of nanoparticles. NLC/LN/SV demonstrated excellent biocompatibility and developed a thin serum protein corona in vitro. Cellular studies showed efficient uptake by A549 cells, G0/G1 arrest, mitochondrial hyperpolarization, reactive oxygen species production, and enhanced cell death compared to free SV. NLC/LN/SV more effectively inhibited cancer cell migration than free SV. Conclusions: NLC/LN/SV represents a promising nanocarrier for SV repurposing, combining enhanced anticancer activity, biocompatibility, and sustained stability for potential lung cancer therapy.
Over 300 million people worldwide suffer from chronic hepatitis B virus (HBV) infections that can cause serious liver damage and hepatocellular carcinoma. Ineffective innate and adaptive immune responses characterize these chronic infections, making the development of a therapeutic vaccine an urgent medical need. While current vaccines can prevent HBV infections, they are ineffective in treating chronic disease. This study investigated lipid nanoparticle (LNP)-formulated nucleoside-modified mRNA vaccines encoding hepatitis B surface antigen (HBsAg) for prophylactic and therapeutic applications. We found that HBsAg mRNA-LNP vaccines induced robust humoral and cellular immune responses, outperforming the protein-based vaccine approved for human use. The incorporation of a major histocompatibility complex class I (MHC class I) signal peptide further enhanced Th1-biased responses preventing HBV infections in a mouse model. Importantly, mRNA-LNP vaccination led to seroconversion, HBsAg clearance, and strong T cell responses in a chronically infected mouse model. These findings highlight the potential of mRNA-LNP as an alternative and effective vaccine modality for HBV prophylaxis and therapeutic use in treating chronic infections.
This study aimed to develop solid lipid nanoparticles (SLNs) loaded with clotrimazole (CLT), itraconazole (ITR), and their combination as potential delivery systems for otomycosis treatment. SLNs were prepared using the emulsification/ultrasonication method with 2.0 % (w/v) cetyl palmitate incorporating 0.1 % (w/w) CLT and/or 0.1 % (w/w) ITR in the lipid matrix and 3.0 % (w/v) Poloxamer 188 as surfactant. The formulations exhibited mean hydrodynamic sizes of 115-130 nm, high encapsulation efficiencies (>80 %), and relevant drug-loading capacities. Structural characterization by X-ray diffraction, small-angle X-ray scattering, differential scanning calorimetry, thermogravimetric analysis, and Fourier-transform infrared spectroscopy confirmed the formation of stable SLNs and successful drug incorporation into the lipid matrix. The three formulations significantly increased drug apparent solubility compared to the pure drugs, with 2224-2387-fold and 760,000-980,000-fold increases for CLT and ITR, respectively. In vitro release studies revealed a sustained release profile best fitting the Korsmeyer-Peppas model. CLT/ITR SLNs demonstrated long-term storage stability over six months at 4 degrees C. Cytotoxicity assays in Vero cells at confirmed good biocompatibility. In vitro antifungal studies against otomycosis-related fungal species demonstrated that CLT-SLN and CLT/ITR-SLN formulations exhibited potent antifungal activity. In this regard, CLT/ITR-SLN formulations exhibited significantly higher activity-up to 16.7-fold compared to CLT and ITR in DMSO and up to 33.3-fold compared to the drug suspensions attributed to the synergistic antifungal effect of both drugs. These findings support CLT/ITR SLNs as a safe and promising strategy for otomycosis treatment. To the best of our knowledge, this is the first report of CLT and ITR co-encapsulation in nanoparticles.
This study presents a novel nanocomposite biomaterial for topical delivery, integrating bacterial cellulose (BC) matrix with Eudragit® (Eu) polymeric nanoparticles (NPs) as an efficient carrier for a bioactive natural extract with hydrophobic properties. BC was produced biotechnologically from Komagataeibacter xylinus, while a propolis extract, known for its potent pharmacological properties, was encapsulated into anionic (Eu S100) and cationic (Eu E100) polymeric NPs using the nanoprecipitation method. These NPs, with mean sizes of 217.2 ± 1.6 nm and 349.2 ± 3.3 nm as determined by Dynamic Light Scattering, were effectively integrated into BC membranes. Scanning Electron Microscopy images revealed the integration of the NPs with the fibers of BC. The nanocomposite’s structural and thermal properties were characterized using Thermogravimetric Analysis, X-ray Diffraction, and Fourier Transform-Infrared spectroscopy. Distinct release profiles of propolis from the BC membranes were observed under different pH conditions (acetate buffer at pH = 5.0 and PBS at pH = 7.0), highlighting their pH environment-responsive behavior. The material demonstrated significant antimicrobial activity against bacteria (S. aureus and B. cereus) and fungi (C. albicans and A. fumigatus), confirmed through agar diffusion assays. Biocompatibility was validated through hemotoxicity and cytotoxicity assessments using mouse skin fibroblast (L929) cells. This innovative combination of biocompatible BC with bioactive polymeric NPs provides an interesting platform for controlled topical drug delivery, combining the properties of both materials for enhanced pharmacological efficacy in wound healing applications.
Lipid nanoparticles (LNPs) were engineered for efficient mRNA delivery and immune enhancement through co-encapsulation of adjuvants. CpG-oligodeoxynucleotides (CpG-ODN, TLR9 agonist) and monophosphoryl lipid A (MPLA, TLR4 agonist) were incorporated to activate intra- and extracellular Toll-like receptor pathways. Formulated via microfluidics, CpG was added in the aqueous phase and MPLA in the lipid phase. The final LNP-MPLA-CpG formulation included Luc mRNA and CpG-ODN (5:1 ratio) with ALC-0315/DSPC/cholesterol/ALC-0159/MPLA (1 %). Particle characterization by DLS and NTA confirmed neutral, homogeneous nanoparticles (∼80 nm). Cryo-TEM and SAXS verified structural integrity. The formulation maintained over 80 % mRNA encapsulation after storage at 4 °C and - 80 °C. Transfection of human and murine dendritic cells (MoDCs and DC2.4) led to robust protein expression. The LNPs showed minimal hemotoxicity and low cytotoxicity, while significantly increasing pro-inflammatory cytokines (IFN-γ, TNF-α, IL-6) in both cell types. DC uptake of LNP-MPLA-CpG was efficient. In the in vivo biodistribution, Luc mRNA was primarily expressed in liver and spleen following intramuscular injection. Serum cytokine levels peaked at 6 h post-injection, and flow cytometry of stimulated splenocytes and liver non-parenchymal cells confirmed a strong innate activation. These results support LNP co-delivery of dual adjuvants as a potent platform for enhancing mRNA vaccine efficacy and innate immune activation.
Lipid nanoparticles (LNPs) tailored for mRNA delivery were optimized to serve as a platform for treating metabolic diseases. Four distinct lipid mixes (LMs) were formulated by modifying various components: LM1 (ALC-0315/DSPC/Cholesterol/ALC-0159), LM2 (ALC-0315/DOPE/Cholesterol/ALC-0159), LM3 (ALC-0315/DSPC/Cholesterol/DMG-PEG2k), and LM4 (DLin-MC3-DMA/DSPC/Cholesterol/ALC-0159). LNPs exhibited stability and homogeneity with a mean size of 75 to 90 nm, confirmed by cryo-TEM and SAXS studies. High mRNA encapsulation (95–100%) was achieved. LNPs effectively delivered EGFP-encoding mRNA to HepG2 and DC2.4 cell lines. LNPs induced cytokine secretion from human peripheral blood mononuclear cells (PBMCs), revealing that LM1, LM2, and LM4 induced 1.5- to 4-fold increases in IL-8, TNF-α, and MCP-1 levels, while LM3 showed minimal changes. Reporter mRNA expression was observed in LNP-treated PBMCs. Hemotoxicity studies confirmed formulation biocompatibility with values below 2%. In vivo biodistribution in mice post intramuscular injection showed significant mRNA expression, mainly in the liver. The modification of LNP components influenced reactogenicity, inflammatory response, and mRNA expression, offering a promising platform for selecting less reactogenic carriers suitable for repetitive dosing in metabolic disease treatment.
IntroductionBovine mastitis is a major infectious disease affecting dairy cattle, impacting public health and milk industry profitability. Staphylococcus aureus is a contagious pathogen responsible for causing bovine subclinical mastitis. Its pathogenesis and antimicrobial resistance highlight the need for alternative treatments, being the nanoencapsulation of essential oils (EO) very promising.MethodsNanostructured lipid carriers (NLCs) containing 5% of Melaleuca armillaris EO were synthesized and characterized. Their physicochemical characteristics, antimicrobial activity against methicillin-resistant and sensitive S. aureus (MRSA and MSSA, respectively), and protective activity against polymorphonuclear cells were evaluated.ResultsNLC-EO nanoparticles were morphologically spherical and the mean size was around 190 nm, Polydispersity index (PdI) was 0.21 (±0.01), Z potential was −18.4 (±0.4) and EO encapsulation efficiency was 71.5%. Of this parameters Z potential was the only which changed after 6 months of storage at four°C, turning into a more negative value of −31.6 (±1.9). NLC-EO showed a biphasic behavior with a fast initial release during the first 6 h, followed by a slow phase for at least 72 h. Free and nanoencapsulated EO had a minimum inhibitory concentration (MIC90) of 6.25 μL/mL; however, free EO had a minimum inhibitory concentrations of biofilm formation (MICB90) of 3.12 μL/mL and for EO nanoencapsulated was 6.25 μL/mL. Minimum inhibitory concentrations of biofilm formation and eradication (MECB90) were 12.5 μL/mL and 6.25 μL/mL for the nanoencapsulated EO and free EO, respectively. Empty NLC inhibited biofilm formation, but not planktonic growth or eradicated preformed biofilms.DiscussionThe EO was efficiently encapsulated and released from NLC, and its antimicrobial activity against MRSA and MSSA was high. Neutrophil viability was higher when EO was encapsulated, being an important result for future experiments evaluating intracellular EO activity, where Staphylococcus aureus survives and evades poorly penetrating antibiotics activity.
In the global context of excessive and indiscriminate application of synthetic agrochemicals, this work combined natural compounds and nanotechnology to develop eco-friendly and sustainable agricultural systems with antifungal action. Cannabis (C) is composed of a large number of phytocannabinoids and terpenes and exhibit important biological properties. Due to the chemical instability of C to avoid their decomposition from environmental exposure, the use of efficient carriers become a promising alternative. Solid Lipid Nanoparticles (SLN) containing C extract were synthesized by homogenization with the ultrasonication method into a lipidic matrix coated with chitosan. The SLN formulations were characterized by dynamic light scattering and field emission scanning electron microscopy, showing a spherical morphology with particles in the range of 150 - 240 nm and low polydispersity indexes. Entrapment efficiency of C was higher than 20% and effectively in vitro released in 24 h. Particularly, the SLN coated with chitosan and loaded with C exhibited an enhanced fungicidal activity against the phytopathogen fungus Fusarium solani sp. Eumartii in a lower concentration than the neat C extract. The results showed a synergistic effect between the positive charges of chitosan and the effect of phytocannabinoids and terpenes of C. These nano-formulations are a promising solution to transform the current agriculture system into a more efficient, eco-friendly and sustainable one.
Gaucher Disease (GD) is a genetic disorder with defective activity of the lysosomal enzyme glucocerebrosidase. Velaglucerasa alfa is a recombinant glucocerebrosidase used for enzyme replacement therapy (ERT) of GD. Due to its limited stability and bioavailability, the use of nanosized systems carrying Velaglucerase alfa is proposed as a novel strategy to improve ERT for GD. Highly stable and low-dispersed Velaglucerase-loaded Eudragit nanoparticles (NPs) (NPs: Vela); 150-160 nm mean size, polydispersity index <0. 15, zeta potential around -32 mV, and 95 % Velaglucerase alfa encapsulation efficiency were obtained. Crystallographic structural analysis by Small Angle X-ray Scattering, confirmed that Velaglucerase alfa was incorporated into the nanoparticle matrix. In vitro studies revealed that NPs: Vela preferentially interact with immunoglobulins and fibrinogen, and a positive enzyme release from NPs:Vela was observed at acidic pH; while no release was observed in neutral conditions. A positive internalization of NPs:Vela in GD mesenchymal stem cells (MSC) was also verified, increasing enzyme cellular activity compared to non-treated cells. Confocal microscopy verified that NPs:Vela colocalized with lysosomes, but no effect of NPs: Vela in the mineralization of MSC was observed. Finally, the viability of GD cell lines is not affected by NPs: Vela, in comparison with Velaglucerase alone, that negatively affects the viability of the target cells. This nanocarrier system for Velaglucerase alfa delivery in lysosomes, initially proposed to improve ERT for GD, may also serve as a starting point to address pathophysiological mechanisms in GD and other lysosomal disorders.
The objective of this study was to develop two lipid nanoparticle (LNP) formulations capable of efficiently expressing a reporter mRNA while co-delivering the anti-inflammatory drug dexamethasone (DX) to reduce inflammatory side effects in protein replacement therapies. Two types of LNPs were developed, in which 25% of cholesterol was replaced by DX. These LNPs contained either 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) or 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) as a helper lipid. The resulting LNPs exhibited high stability, homogeneity, and near-neutral Zeta potentials. SAXS experiments confirmed DX incorporation into the LNP core, with slow in vitro DX release observed over 48 h. The LNPs achieved high mRNA encapsulation efficiency (95–100%) and effectively transfected HepG2 cells, dendritic cells, and hPBMCs. While LNPs increased cytokine release (IL-1β, TNF-α, MCP-1), LNPs-DX significantly reduced cytokine levels, demonstrating enhanced anti-inflammatory properties while maintaining mRNA expression levels. In vivo biodistribution showed predominant liver localization post-intramuscular injection, regardless of the DSPC or DOPE composition. LNPs co-loaded with mRNA and DX are promising candidates for continuous protein replacement. Due to their ability to reduce treatment-related inflammation while maintaining significant mRNA expression levels, these LNPs are perfectly suited for the treatment of liver-related metabolic diseases.
Plant and herbal essential oils (EOs) offer a wide range of pharmacological actions that include anticancer effects. Here, we evaluated the cytotoxic activity of EO from Lippia alba (chemotype linalool), L. alba (chemotype dihydrocarvone, LaDEO), Clinopodium nepeta (L.) Kuntze (CnEO), Eucalyptus globulus, Origanum × paniculatum, Mentha × piperita, Mentha arvensis L., and Rosmarinus officinalis L. against human lung (A549) and colon (HCT-116) cancer cells. The cells were treated with increasing EO concentrations (0–500 µL/L) for 24 h, and cytotoxic activity was assessed. LaDEO and CnEO were the most potent EOs evaluated (IC50 range, 145–275 µL/L). The gas chromatography–mass spectrometry method was used to determine their composition. Considering EO limitations as therapeutic agents (poor water solubility, volatilization, and oxidation), we evaluated whether LaDEO and CnEO encapsulation into solid lipid nanoparticles (SLN/EO) enhanced their anticancer activity. Highly stable spherical SLN/LaDEO and SLN/CnEO SLN/EO were obtained, with a mean diameter of 140–150 nm, narrow size dispersion, and Z potential around −5mV. EO encapsulation strongly increased their anticancer activity, particularly in A549 cells exposed to SLN/CnEO (IC50 = 66 µL/L CnEO). The physicochemical characterization, biosafety, and anticancer mechanisms of SLN/CnEO were also evaluated in A549 cells. SLN/CnEO containing 97 ± 1% CnEO was highly stable for up to 6 months. An increased in vitro CnEO release from SLN at an acidic pH (endolysosomal compartment) was observed. SLN/CnEO proved to be safe against blood components and non-toxic for normal WI-38 cells at therapeutic concentrations. SLN/CnEO substantially enhanced A549 cell death and cell migration inhibition compared with free CnEO.
Geraniol (GOH) is a linear monoterpene alcohol found in essential oils of plants and herbs with multiple pharmacological properties, including anticancer activity. Due to its poor water solubility and volatility, GOH stability, administration, and bioavailability in physiological conditions should be improved to develop efficient carrier systems. Thus, GOH was encapsulated into nanostructured lipid carriers (NLC) as a novel strategy to improve its anticancer activity. Highly stable and lowly dispersed GOH-loaded NLC (NLC/GOH); 110 nm mean size, polydispersity index ([PDI] < 0.2), Zeta potential around-10mV, and 95% GOH encapsulation efficiency were obtained. After GOH inclusion, the crystallographic structure of NLC changed according to wide-and small -angle X-ray scattering studies. An increased in vitro GOH release from NLC at acidic pH (tumoral environment) after 24 h was observed. The NLC/GOH proved to be safe against blood components, adsorbed in vitro a thin layer of serum proteins, and preferentially interacted with human serum albumin compared with plasmatic opsonins. An efficient time-dependent cellular uptake of NLC/GOH was observed in A549 cells after 24 h. The A549 cell viability loss was increased (1.8-3.2 fold) after GOH encapsulation into NLC, which also enhanced mitochondrial membrane depolarization and cell death. Highly cytotoxic concentrations of NLC/GOH against A549 cells resulted non-toxic to normal lung fibroblasts WI-38 cells. Finally, GOH nanoencapsulation into NLC potentiated the inhibition of A549 cell migration exerted by free GOH.