Açaí (Euterpe oleracea Mart.) Seed Oil and Its Nanoemulsion: Chemical Characterisation, Toxicity Evaluation, Antioxidant and Anticancer Activities.

This study explores a nanoemulsion formulated with açaí seed oil, known for its rich fatty acid composition and diverse biological activities. This study aimed to characterise a nanoemulsion formulated with açaí seed oil and explore its cytotoxic effects on HeLa and SiHa cervical cancer cell lines, alongside assessing its antioxidant and toxicity properties both in vitro and in vivo. Extracted from fruits sourced in Brazil, the oil underwent thorough chemical characterization using gas chromatography-mass spectrometry. The resulting nanoemulsion was prepared and evaluated for stability, particle size, and antioxidant properties. The nanoemulsion exhibited translucency, fluidity, and stability post centrifugation and temperature tests, with a droplet size of 238.37, PDI -9.59, pH 7, and turbidity 0.267. In vitro assessments on cervical cancer cell lines revealed antitumour effects, including inhibition of cell proliferation, migration, and colony formation. Toxicity tests conducted in cell cultures and female Swiss mice demonstrated no adverse effects of both açaí seed oil and nanoemulsion. Overall, açaí seed oil, particularly when formulated into a nanoemulsion, presents potential for cancer treatment due to its bioactive properties and safety profile.

Extracellular vesicles from the mycoparasitic fungus Trichoderma harzianum.

Trichoderma harzianum is a filamentous fungus that can act as a mycoparasite, saprophyte, or a plant symbiotic. It is widely used as a biological control agent against phytopathogenic fungi and can also be used for plant growth promotion and biofortification. Interaction between T. harzianum and phytopathogenic fungi involves mycoparasitism, competition, and antibiosis. Extracellular vesicles (EVs) have been described as presenting a central role in mechanisms of communication and interaction among fungus and their hosts. In this study, we characterized extracellular vesicles of T. harzianum produced during growth in the presence of glucose or S. sclerotiorum mycelia. A set of vesicular proteins was identified using proteomic approach, mainly presenting predicted signal peptides.

Pharmacokinetics and pharmacodynamics of dextroketamine alone or combined with midazolam in Caiman crocodilus.

Pharmacokinetics studies of anesthetic agents are important for understanding of the pharmacology and metabolism of anesthetic agents in reptilians. This study was designed to examine the pharmacokinetic and pharmacodynamic properties of intravenous dextroketamine alone or combined with midazolam in Caiman crocodilus. Eight caimans were anesthetized with dextroketamine (10 mg/kg; group D) or dextroketamine and midazolam (10 and 0.5 mg/kg respectively; group DM) into the occipital venous sinus. The pharmacokinetic parameters were calculated by HPLC using a non-compartmental modeling. Serial blood samples were collected at baseline and within 15 and 30 min, and 11.5, 2, 4, 8, 12, 24 and 48 h of drug administration. Sedation status over time differed between groups. All animals in group D (8/8; 100%) showed signs of light sedation at t10. Half (4/8; 50%) of these caimans did not progress to deeper levels of sedation. In spite of light sedation at t10, animals in group DM were deeply sedated within 13.13 ± 7.04 min of anesthetic agent injection. The area under the plasma concentration-time curve (AUC0-48) and half-life of dextroketamine changed significantly after combination with midazolam. Even without significant changes in clearance, the almost two-fold increase in the half-life of dextroketamine suggests a slower rate of elimination.

Plasma concentration, cardiorespiratory and analgesic effects of ketamine-fentanyl infusion in dogs submitted to mastectomy.

BACKGROUND: The analgesic and cardiorespiratory effects of ketamine, fentanyl, or ketamine-fentanyl constant rate infusion (CRI) in dogs undergoing mastectomy were evaluated. Seventeen female dogs received CRI of ketamine (GK [n = 6]: bolus 0.5 mg/kg; CRI 20 µg/kg/min in intra- and postoperative periods], fentanyl (GF [n = 5]: bolus 20 µg/kg; intraoperative CRI 5 20 µg/kg/hour and postoperative CRI 2 20 µg/kg/hour), or combination of ketamine-fentanyl (GKF [n = 6]: aforementioned doses) for 8 h. Cardiorespiratory, blood gas analyses, plasma drug concentrations, sedation score (SS), Pain Scores were evaluated. RESULTS: The heart rate decreased in the GF and GKF (p < 0.04); the mean arterial pressure was lower in the GKF than in the GK at 35 min (p < 0.001). Maximum plasma concentrations were observed 5 min after bolus in the GK (2847.06 ± 2903.03 ng/mL) and GKF (2811.20 ± 1931.76 ng/mL). Plasma concentration in intraoperative period of ketamine was of > 100 ng/mL in 5/5 and 2/5 animals in the GKF and GK, respectively; and > 1.1 ng/mL of fentanyl in 4/5 and 3/5 in GKF and GF, respectively. CONCLUSION: Ketamine with/without fentanyl provided analgesia without significant cardiorespiratory and guaranteed the minimal plasma levels with analgesic potential during the 8 h.

Topical application of melatonin accelerates the maturation of skin wounds and increases collagen deposition in a rat model of diabetes.

AIMS: This study aimed to evaluate the cicatricial potential of melatonin when applied to wounds of diabetic rats. MATHERIALS AND METHODS: The formulation containing melatonin was developed and applied topically to cutaneous wounds of diabetic rats. 48 Wistar rats were used, divided into two groups of 24 diabetic animals each: (i) control group (CG), the animals received topical application of the no-melatonin formulation; (ii) treatment group (TG), the animals received topical application of the melatonin-containing formulation. All animals in each group were treated at four time points: 3, 7, 14, and 21 days. Each subgroup consisted of six animals. RESULTS: The treatment with melatonin improved wound healing by promoting wound closure earlier than the control group evaluated. Also improved a better resolution of the inflammatory phase observed mainly at 7 days, higher tissue maturation and expressive collagen deposition. CONCLUSION: The observed data reveal that the use of melatonin topically could be a promising strategy for the healing of wounds in diabetes. The results of this study elucidate the effects of previously described pathways in which it is proposed that melatonin acts promoting wound healing in diabetes.

Increased Nose-to-Brain Delivery of Melatonin Mediated by Polycaprolactone Nanoparticles for the Treatment of Glioblastoma.

PURPOSE: Intranasal administration has been extensively applied to deliver drugs to the brain. In spite of its unfavorable biopharmaceutic properties, melatonin (MLT) has demonstrated anticancer effects against glioblastoma. This study describes the nose-to-brain delivery of MLT-loaded polycaprolactone nanoparticles (MLT-NP) for the treatment of glioblastoma. METHODS: MLT-NP were prepared by nanoprecipitation. Following intranasal administration in rats, brain targeting of the formulation was demonstrated by fluorescence tomography. Brain and plasma pharmacokinetic profiles were analyzed. Cytotoxicity against U87MG glioblastoma cells and MRC-5 non-tumor cells was evaluated. RESULTS: MLT-NP increased the drug apparent water solubility ~35 fold. The formulation demonstrated strong activity against U87MG cells, resulting in IC50 ~2500 fold lower than that of the free drug. No cytotoxic effect was observed against non-tumor cells. Fluorescence tomography images evidenced the direct translocation of nanoparticles from nasal cavity to the brain. Intranasal administration of MLT-NP resulted in higher AUCbrain and drug targeting index compared to the free drug by either intranasal or oral route. CONCLUSIONS: Nanoencapsulation of MLT was crucial for the selective antitumoral activity against U87MG. In vivo evaluation confirmed nose-to-brain delivery of MLT mediated by nanoparticles, highlighting the formulation as a suitable approach to improve glioblastoma therapy.

Antiproliferative Activity and VEGF Expression Reduction in MCF7 and PC-3 Cancer Cells by Paclitaxel and Imatinib Co-encapsulation in Folate-Targeted Liposomes.

Co-encapsulation of anticancer drugs paclitaxel and imatinib in nanocarriers is a promising strategy to optimize cancer treatment. Aiming to combine the cytotoxic and antiangiogenic properties of the drugs, a liposome formulation targeted to folate receptor co-encapsulating paclitaxel and imatinib was designed in this work. An efficient method was optimized for the synthesis of the lipid anchor DSPE-PEG(2000)-folic acid (FA). The structure of the obtained product was confirmed by RMN, FT-IR, and ESI-MS techniques. A new analytical method was developed and validated for simultaneous quantification of the drugs by liquid chromatography. Liposomes, composed of phosphatidylcholine, cholesterol, and DSPE-mPEG(2000), were prepared by extrusion. Their surface was modified by post-insertion of DSPE-PEG(2000)-FA. Reaction yield for DSPE-PEG(2000)-FA synthesis was 87%. Liposomes had a mean diameter of 122.85 ± 1.48 nm and polydispersity index of 0.19 ± 0.01. Lyophilized formulations remained stable for 60 days in terms of size and drug loading. FA-targeted liposomes had a higher effect on MCF7 cell viability reduction (p < 0.05) when compared with non-targeted liposomes and free paclitaxel. On PC-3 cells, viability reduction was greater (p < 0.01) when cells were exposed to targeted vesicles co-encapsulating both drugs, compared with the non-targeted formulation. VEGF gene expression was reduced in MCF7 and PC-3 cells (p < 0.0001), with targeted vesicles exhibiting better performance than non-targeted liposomes. Our results demonstrate that multifunctional liposomes associating molecular targeting and multidrug co-encapsulation are an interesting strategy to achieve enhanced internalization and accumulation of drugs in targeted cells, combining multiple antitumor strategies.

Development of a High-Performance Liquid Chromatographic Method for Asiaticoside Quantification in Different Skin Layers after Topical Application of a Centella asiatica Extract.

The topical application of Centella asiatica extract has been commonly used for many different purposes but especially for cosmetic use in the treatment of gynoid lipodystrophy. Asiaticoside, the most active component in this extract, is responsible for its therapeutic activities. However, little is known to date about asiaticoside skin penetration. Thus, an analytical method for asiaticoside quantification in different skin layers after the topical application of C. asiatica extract was developed and skin permeation studies were performed with the plant extract to apply the analytical method developed. An extraction procedure to recover asiaticoside from the biological matrix was also developed. Asiaticoside was assayed by HPLC/UV (high-performance liquid chromatography-ultraviolet detection) using a gradient of ACN (acetonitrile) and 0.2% phosphoric acid (flow rate of 1.0 mL/min). The analytical procedure was validated according to U. S. Food and Drug Administration guidelines. Selectivity was shown, as endogenous skin components did not interfere with the asiaticoside peak. Analytical curve was linear (3 to 60 µg/mL) and the lower limit of quantification was determined (3 µg/mL). Asiaticoside recoveries from skin samples were 95.1% and 66.7% for the stratum corneum and remaining skin, respectively. After 48 h of in vitro permeation studies, a substantial amount of asiaticoside was quantified in the skin layers. The presence of asiaticoside was also detected in the receptor solution of Franz diffusion cells after 48 h (5.81 ± 1.00 µg/mL). The method was reliable and reproducible for asiaticoside quantification in skin samples, thereby making it possible to determine the cutaneous penetration profile of this drug in permeation studies.

Compacted Multiparticulate Systems for Colon-Specific Delivery of Ketoprofen.

Pellet-containing tablets for colon-specific drug delivery present higher targeting efficiency and lower costs when compared with monolithic tablets and pellet-filled capsules, respectively. In this study, pellets containing ketoprofen were coated with different acrylic polymers and submitted to compaction. The influence of formulation and process factors on film integrity was then evaluated. Pellets were prepared via extrusion-spheronization and coated using two acrylic polymers (Eudragit® FS 30 D and Opadry® 94 k28327, PMMA and PMA, respectively). The resulting pellets were mixed with placebo granules and compressed in a hydraulic press. Multiple regression showed that ketoprofen release from pellet-containing tablets is predominantly influenced by pellet content, hardness, friability, and disintegration time. PMA-containing tablets prepared under low compaction force or with low pellet content showed rapid disintegration (<1 min) and ketoprofen release similar to those of uncompressed coated pellets (∼30% at 360 min of experiment). On the other hand, PMMA-containing tablets showed a higher rupture level, and those prepared with higher pellet content gave rise to a non-disintegrating matrix. Coated pellets were shown to be able to target ketoprofen to the colonic region. Targeting capacity was dependent on the physicochemical characteristics of the tablets.

4-Nerolidylcatechol: apoptosis by mitochondrial mechanisms with reduction in cyclin D1 at G0/G1 stage of the chronic myelogenous K562 cell line.

CONTEXT: 4-Nerolidylcatechol (4-NRC) has showed antitumor potential through apoptosis. However, its apoptotic mechanisms are still unclear, especially in leukemic cells. OBJECTIVES: To evaluate the cytotoxic potential of 4-NRC and its cell death pathways in p53-null K562 leukemic cells. MATERIALS AND METHODS: Cytotoxicity of 4-NRC (4.17-534.5 µM) over 24 h of exposure was evaluated by MTT assay. 4-NRC-induced apoptosis in K562 cells was investigated by phosphatidylserine (PS) externalization, cell cycle, sub-G1, mitochondrial evaluation, cytochrome c, cyclin D1 and intracellular reactive oxygen species (ROS) levels, and caspase activity analysis. RESULTS: IC50 values obtained were 11.40, 27.31, 15.93 and 15.70 µM for lymphocytes, K562, HL-60 and Jurkat cells, respectively. In K562 cells, 4-NRC (27 µM) promoted apoptosis as verified by cellular morphological changes, a significant increase in PS externalization and sub-G1 cells. Moreover, it significantly arrested the cells at the G0/G1 phase due to a reduction in cyclin D1 expression. These effects of 4-NRC also significantly promoted a reduction in mitochondrial activity and membrane depolarization, accumulation of cytosolic cytochrome c and ROS overproduction. Additionally, it triggered an increase in caspases -3/7, -8 and -9 activities. When the cells were pretreated with N-acetyl-l-cysteine ROS scavenger, 4-NRC-induced apoptosis was partially blocked, which suggests that it exerts cytotoxicity though not exclusively through ROS-mediated mechanisms. DISCUSSION AND CONCLUSION: 4-NRC has antileukemic properties, inducing apoptosis mediated by mitochondrial-dependent mechanisms with cyclin D1 inhibition. Given that emerging treatment concepts include novel combinations of well-known agents, 4-NRC could offer a promising alternative for chemotherapeutic combinations to maximize tumour suppression.

Improvement of enalapril maleate chemical stability by high shear melting granulation.

Enalapril maleate is a widely used drug, which is chemically unstable when mixed with excipients resulting in enalaprilat and diketopiperazine as the main degradation products. The preparation of enalapril sodium salt has been used to improve drug stability in solid dosage forms; however, product rejection is observed when the chemical reaction for obtaining the sodium salt is not completely finished before packaging. In this study, granules were prepared by melting granulation using stearic acid or glyceryl monostearate, with a view to developing more stable enalapril maleate solid dosage forms. The granules were prepared in a laboratory-scale high shear mixer and compressed in a rotary machine. Size distribution, flow properties, in vitro drug release and enalapril maleate chemical stability were evaluated and compared with data obtained from tablets prepared without hydrophobic binders. All formulations showed good physical properties and immediate drug release. The greatest improvement in the enalapril maleate stability was observed in formulations containing stearic acid. This study showed that hot melting granulation could be successfully used to prepare enalapril maleate granules which could substitute the in situ formation of enalapril sodium salt, since they provided better enalapril stability in solid dosage forms.

Multicompartimental nanoparticles for co-encapsulation and multimodal drug delivery to tumor cells and neovasculature.

PURPOSE: The purpose of this work was the development of a multicompartimental nanocarrier for the simultaneous encapsulation of paclitaxel (PTX) and genistein (GEN), associating antiangiogenic and cytotoxic properties in order to potentiate antitumoral activity. METHOD: Polymeric nanocapsules containing PTX were obtained by interfacial deposition of preformed polymer and coated with a phospholipid bilayer entrapping GEN. Physical-chemical and morphological characteristics were characterized, including size and size distribution, drug entrapment efficiency and drug release profile. In vivo studies were performed in EAT bearing Swiss mice. RESULTS: Entrapment efficiency for both drugs in the nanoparticles was approximately 98%. Average particle diameter was 150 nm with a monomodal distribution. In vitro assays showed distinct temporal drug release profiles for each drug. The dose of 0.2 mg/kg/day of PTX resulted in 11% tumor inhibition, however the association of 12 mg/kg/day of GEN promoted 44% tumor inhibition and a 58% decrease in VEGF levels. CONCLUSIONS: Nanoparticles containing GEN and PTX with a temporal pattern of drug release indicated that the combined effect of cytotoxic and antiangiogenic drugs present in the formulation contributed to the overall enhanced antitumor activity of the nanomedicine.

Near Infrared Biomimetic Hybrid Magnetic Nanocarrier for MRI-Guided Thermal Therapy.

Cell-membrane hybrid nanoparticles (NPs) are designed to improve drug delivery, thermal therapy, and immunotherapy for several diseases. Here, we report the development of distinct biomimetic magnetic nanocarriers containing magnetic nanoparticles encapsulated in vesicles and IR780 near-infrared dyes incorporated in the membranes. Distinct cell membranes are investigated, red blood cell (RBC), melanoma (B16F10), and glioblastoma (GL261). Hybrid nanocarriers containing synthetic lipids and a cell membrane are designed. The biomedical applications of several systems are compared. The inorganic nanoparticle consisted of Mn-ferrite nanoparticles with a core diameter of 15 ± 4 nm. TEM images show many multicore nanostructures (∼40 nm), which correlate with the hydrodynamic size. Ultrahigh transverse relaxivity values are reported for the magnetic NPs, 746 mM-1s-1, decreasing respectively to 445 mM-1s-1 and 278 mM-1s-1 for the B16F10 and GL261 hybrid vesicles. The ratio of relaxivities r2/r1 decreased with the higher encapsulation of NPs and increased for the biomimetic liposomes. Therapeutic temperatures are achieved by both, magnetic nanoparticle hyperthermia and photothermal therapy. Photothermal conversion efficiency ∼25-30% are reported. Cell culture revealed lower wrapping times for the biomimetic vesicles. In vivo experiments with distinct routes of nanoparticle administration were investigated. Intratumoral injection proved the nanoparticle-mediated PTT efficiency. MRI and near-infrared images showed that the nanoparticles accumulate in the tumor after intravenous or intraperitoneal administration. Both routes benefit from MRI-guided PTT and demonstrate the multimodal theranostic applications for cancer therapy.

Photothermal Properties of IR-780-Based Nanoparticles Depend on Nanocarrier Design: A Comparative Study on Synthetic Liposomes and Cell Membrane and Hybrid Biomimetic Vesicles.

Biomimetic nanoparticles hold great promise for photonic-mediated nanomedicine due to the association of the biological functionality of the membrane with the physical/chemical goals of organic/inorganic structures, but studies involving fluorescent biomimetic vesicles are still scarce. The purpose of this article is to determine how photothermal therapy (PTT) with theranostic IR-780-based nanoparticles depends on the dye content, cholesterol content, lipid bilayer phase and cell membrane type. The photophysical responses of synthetic liposomes, cell membrane vesicles and hybrid nanoparticles are compared. The samples were characterized by nanoparticle tracking analysis, photoluminescence, electron spin resonance, and photothermal- and heat-mediated drug release experiments, among other techniques. The photothermal conversion efficiency (PCE) was determined using Roper's method. All samples excited at 804 nm showed three fluorescence bands, two of them independent of the IR-780 content. Samples with a fluorescence band at around 850 nm showed photobleaching (PBL). Quenching was higher in cell membrane vesicles, while cholesterol inhibited quenching in synthetic liposomes with low dye content. PTT depended on the cell membrane and was more efficient for melanoma than erythrocyte vesicles. Synthetic liposomes containing cholesterol and a high amount of IR-780 presented superior performance in PTT experiments, with a 2.4-fold PCE increase in comparison with free IR-780, no PBL and the ability to heat-trigger doxorubicin release.

Development and validation of a simple and rapid liquid chromatography method for the determination of genistein in skin permeation studies.

Genistein (GEN) has potential advantages for topical skin delivery, but no literature data are available for its quantitation in different skin layers, such as the stratum corneum (SC). Therefore, a simple, rapid, selective and sensitive bioanalytical method was developed and validated for GEN quantitation in porcine skin samples following in vitro permeation studies. GEN was assayed by HPLC with UV-Vis detection (270 nm) using 0.5% acetic acid in water-n-propanol-acetonitrile (50 : 2 : 48, v/v/v) as mobile phase (flow-rate of 1.0 mL/min). Specificity was demonstrated since endogenous skin components did not interfere with GEN peak. Standard analytical curve was linear over the concentration range (0.1-60 µg/mL) and the lower limit of quantitation was determined for different skin layers (100 ng/mL). GEN recovery from skin layers ranged from 95.57 to 97.57%. Permeation studies were carried out using an automated vertical diffusion cell apparatus. No fluctuation on the amount of GEN retained in the SC was observed over time, but increasing amounts of the drug were found in deeper layers of the skin. The method was reliable and reproducible for the quantitation GEN in skin samples enabling the determination of the cutaneous penetration profile of this drug in permeation experiments.

Preparation, characterization and in vitro antimicrobial activity of liposomal ceftazidime and cefepime against Pseudomonas aeruginosa strains.

Pseudomonas aeruginosa is an opportunistic microorganism with the ability to respond to a wide variety of environmental changes, exhibiting a high intrinsic resistance to a number of antimicrobial agents. This low susceptibility to antimicrobial substances is primarily due to the low permeability of its outer membrane, efflux mechanisms and the synthesis of enzymes that promote the degradation of these drugs. Cephalosporins, particularty ceftazidime and cefepime are effective against P. aeruginosa, however, its increasing resistance has limited the usage of these antibiotics. Encapsulating antimicrobial drugs into unilamellar liposomes is an approach that has been investigated in order to overcome microorganism resistance. In this study, antimicrobial activity of liposomal ceftazidime and cefepime against P. aeruginosa ATCC 27853 and P. aeruginosa SPM-1 was compared to that of the free drugs. Liposomal characterization included diameter, encapsulation efficiency and stability. Minimum Inhibitory Concentration (MIC) was determined for free and liposomal forms of both drugs. Minimum Bactericidal Concentration (MBC) was determined at concentrations 1, 2 and 4 times MIC. Average diameter of liposomes was 131.88 nm and encapsulation efficiency for cefepime and ceftazidime were 2.29% end 5.77%, respectively. Improved stability was obtained when liposome formulations were prepared with a 50% molar ratio for cholesterol in relation to the phospholipid. MIC for liposomal antibiotics for both drugs were 50% lower than that of the free drug, demonstrating that liposomal drug delivery systems may contribute to increase the antibacterial activity of these drugs.

Interplay between mucus mobility and alveolar macrophage targeting of surface-modified liposomes.

Alveolar macrophages play a crucial role in the initiation and resolution of the immune response in the lungs. Pro-inflammatory M1 alveolar macrophages are an interesting target for treating inflammatory and infectious pulmonary diseases. One commune targeting strategy is to use nanoparticles conjugated with hyaluronic acid, which interact with CD44 overexpressed on the membrane of those cells. Unfortunately, this coating strategy may be countered by the presence on the surface of the nanoparticles of a poly(ethylene glycol) corona employed to improve nanoparticles' diffusion in the lung mucus. This study aims to measure this phenomenon by comparing the behavior in a murine lung inflammation model of three liposomal platforms designed to represent different poly(ethylene glycol) and hyaluronic acid densities (Liposome-PEG, Liposome-PEG-HA and Liposome-HA). In this work, the liposomes were obtained by a one-step ethanol injection method. Their interaction with mucin and targeting ability toward pro-inflammatory macrophages were then investigated in vitro and in vivo in a LPS model of lung inflammation. In vitro, poly(ethylene glycol) free HA-liposomes display a superior targeting efficiency toward M1 macrophages, while the addition of poly(ethylene glycol) induces better mucus mobility. Interestingly in vivo studies revealed that the three liposomes showed distinct cell specificity with alveolar macrophages demonstrating an avidity for poly(ethylene glycol) free HA-liposomes, while neutrophils favored PEGylated liposomes exempt of HA. Those results could be explained by the presence of two forces exercising a balance between mucus penetration and receptor targeting. This study corroborates the importance of considering the site of action and the targeted cells when designing nanoparticles to treat lung diseases.

Innate and adaptive immune responses toward nanomedicines.

Since the commercialization of the first liposomes used for drug delivery, Doxil/Caelyx® and Myocet®, tremendous progress has been made in understanding interactions between nanomedicines and biological systems. Fundamental work at the interface of engineering and medicine has allowed nanomedicines to deliver therapeutic small molecules and nucleic acids more efficiently. While nanomedicines are used in oncology for immunotherapy or to deliver combinations of cytotoxics, the clinical successes of gene silencing approaches like patisiran lipid complexes (Onpattro®) have paved the way for a variety of therapies beyond cancer. In parallel, the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has highlighted the potential of mRNA vaccines to develop immunization strategies at unprecedented speed. To rationally design therapeutic and vaccines, chemists, materials scientists, and drug delivery experts need to better understand how nanotechnologies interact with the immune system. This review presents a comprehensive overview of the innate and adaptative immune systems and emphasizes the intricate mechanisms through which nanomedicines interact with these biological functions.

Safety and efficacy of a mucoadhesive phytomedication containing curcuminoids and Bidens pilosa L. extract in the prevention and treatment of radiochemotherapy-induced oral mucositis: Triple-blind, randomized, placebo-controlled, clinical trial.

BACKGROUND: Oral mucositis (OM) is the significant complication of radio/chemotherapy treatment. This study evaluated the safety and efficacy of a mucoadhesive phytomedication containing curcuminoids and Bidens pilosa L. (FITOPROT) in the prevention/treatment of OM. METHODS: Sixty-two patients were randomized into the group's intervention and placebo. Adverse effect assessment, OM grading, pain, and saliva collection were carried at the 1st, 15th, 21st, and final of radiotherapy (RT). Inflammatory salivary mediators were measured. RESULTS: FITOPROT decreased the severity of OM from the 15th to the final RT, while the placebo showed an increase in the severity (p < 0.05). Intervention group had a lower number of patients with ulcerated OM at the final RT (p < 0.05). Phytomedication prevented increases of IL-8 levels and reduced the salivary nitrite during RT. CONCLUSIONS: FITOPROT does not promote adverse effects, it appears to be effective at reducing the severity of OM, and it controls the concentration of pro-inflammatory mediators.

Biological effects of formulation containing curcuminoids and Bidens Pilosa L. in oral carcinoma cell line.

FITOPROT, which contains curcuminoids and Bidens pilosa L. extract, is an innovative mucoadhesive formulation indicated for the topical treatment of chemoradiotherapy-induced oral mucositis (OM) in patients with advanced and visible oral squamous cell carcinoma. The formulation is used as a mouthwash directly on tumor tissue of patients with advanced neoplasms, without triggering cancer cell proliferation or tumor invasiveness. Thus, the aim of this study was to evaluate the biological effects of FITOPROT on an oral squamous cell carcinoma cell line (SCC-4). The viability of SCC-4 cells was assessed after exposure to FITOPROT using MTT reduction assay. The effects of the mucoadhesive formulation on cell cycle progression and cell death parameters were evaluated using flow cytometry. In addition, the inflammatory profile of the tumor cells was evaluated using the cytometric bead array (CBA) assay. FITOPROT promoted a concentration-dependent decrease in cell viability and cell cycle arrest at the G2/M phase (p < 0.05). Mitochondrial membrane potential was also altered after exposure to the formulation (p < 0.05), in parallel with a reduction in VEGF and IL-8 production (p = 0.01 and p = 0.05, respectively). In summary, the results indicate that FITOPROT reduces SCC-4 cell viability, promotes cell cycle arrest, modulates mitochondrial membrane potential, and exhibits antiangiogenic and anti-inflammatory properties, thus indicating its potential for topical use in patients with OM and visible tumors in the mouth.