Co-Delivery of an Innovative Organoselenium Compound and Paclitaxel by pH-Responsive PCL Nanoparticles to Synergistically Overcome Multidrug Resistance in Cancer.

In this study, we designed the association of the organoselenium compound 5'-Seleno-(phenyl)-3'-(ferulic-amido)-thymidine (AFAT-Se), a promising innovative nucleoside analogue, with the antitumor drug paclitaxel, in poly(ε-caprolactone) (PCL)-based nanoparticles (NPs). The nanoprecipitation method was used, adding the lysine-based surfactant, 77KS, as a pH-responsive adjuvant. The physicochemical properties presented by the proposed NPs were consistent with expectations. The co-nanoencapsulation of the bioactive compounds maintained the antioxidant activity of the association and evidenced greater antiproliferative activity in the resistant/MDR tumor cell line NCI/ADR-RES, both in the monolayer/two-dimensional (2D) and in the spheroid/three-dimensional (3D) assays. Hemocompatibility studies indicated the safety of the nanoformulation, corroborating the ability to spare non-tumor 3T3 cells and human mononuclear cells of peripheral blood (PBMCs) from cytotoxic effects, indicating its selectivity for the cancerous cells. Furthermore, the synergistic antiproliferative effect was found for both the association of free compounds and the co-encapsulated formulation. These findings highlight the antitumor potential of combining these bioactives, and the proposed nanoformulation as a potentially safe and effective strategy to overcome multidrug resistance in cancer therapy.

Size Matters? A Comprehensive In Vitro Study of the Impact of Particle Size on the Toxicity of ZnO.

This study describes a comparative in vitro study of the toxicity behavior of zinc oxide (ZnO) nanoparticles and micro-sized particles. The study aimed to understand the impact of particle size on ZnO toxicity by characterizing the particles in different media, including cell culture media, human plasma, and protein solutions (bovine serum albumin and fibrinogen). The particles and their interactions with proteins were characterized in the study using a variety of methods, including atomic force microscopy (AFM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). Hemolytic activity, coagulation time, and cell viability assays were used to assess ZnO toxicity. The results highlight the complex interactions between ZnO NPs and biological systems, including their aggregation behavior, hemolytic activity, protein corona formation, coagulation effects, and cytotoxicity. Additionally, the study indicates that ZnO nanoparticles are not more toxic than micro-sized particles, and the 50 nm particle results were, in general, the least toxic. Furthermore, the study found that, at low concentrations, no acute toxicity was observed. Overall, this study provides important insights into the toxicity behavior of ZnO particles and highlights that no direct relationship between nanometer size and toxicity can be directly attributed.

Comparison of the analgesic effect of inhaled lavender vs vanilla essential oil for neonatal frenotomy: a randomized clinical trial (NCT04867824).

It is necessary to treat neonatal pain because it may have short- and long-term adverse effects. Frenotomy is a painful procedure where sucking, a common strategy to relieve pain, cannot be used because the technique is performed on the tongue. In a previous randomized clinical trial, we demonstrated that inhaled lavender essential oil (LEO) reduced the signs of pain during neonatal frenotomy. We aimed to find out whether inhaled vanilla essential oil (VEO) is more effective in reducing pain during frenotomy than LEO. Randomized clinical trial with neonates who underwent a frenotomy for type 3 tongue-ties between May and October 2021. Pain was assessed using pre and post-procedure heart rate (HR) and oxygen saturation (SatO2), crying time, and NIPS score. Neonates were randomized into "experimental" and "control" group. In both groups, we performed swaddling, administered oral sucrose, and let the newborn suck for 2 min. We placed a gauze pad with one drop of LEO (control group) or of VEO (experimental group) under the neonate's nose for 2 min prior to and during the frenotomy. We enrolled 142 neonates (71 per group). Both groups showed similar NIPS scores (2.02 vs 2.38) and crying times (15.3 vs 18.7 s). We observed no differences in HR increase or in SatO2 decrease between both groups. We observed no side effects in either of the groups. CONCLUSIONS: We observed no appreciable difference between LEO and VEO; therefore, we cannot conclude which of them was more effective in treating pain in neonates who underwent a frenotomy. TRIAL REGISTRATION:  This clinical trial is registered with www. CLINICALTRIALS: gov with NCT04867824. WHAT IS KNOWN: • Pain management is one of the most important goals of neonatal care as it can have long-term neurodevelopmental effects. • Lavender essential oil can help relieve pain due to its sedative, antispasmodic, and anticolic properties. WHAT IS NEW: • Lavender and vanilla essential oils are safe, beneficial, easy to use, and cheap in relieving pain in neonates who undergo a frenotomy for type 3 tongue-ties.

Exploring wild Aspleniaceae ferns as safety sources of polyphenols: The case of Asplenium trichomanes L. and Ceterach officinarum Willd.

The forest ecosystem is a source of material resources used since ancient times by mankind. Ferns are part of different oriental systems of traditional medicine due to the phytochemical variety of their fronds, which have allowed their traditional use to be validated through ethnopharmacological studies. In Europe, different cultures have used the same fern with a wide variety of applications due to its presence in most European forests. In recent years, studies on the phytocharacterization and biological activity of the fronds of the main European ferns have been published. In this study, the presence of polyphenolic phytochemicals has been evaluated by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) in the fronds of two wild ferns together with in vitro activities in non-tumoral and human tumoral cell lines. The polyphenols were extracted from Asplenium trichomanes L. and Ceterach officinarum Willd. by cold maceration using methanol. The main phytochemicals of polyphenolic origin in the extracts of A. trichomanes and C. officinarum determined by HPLC-MS/MS were the flavonol hyperoside and the phenolic acid chlorogenic acid, respectively. This different polyphenolic nature of both extracts contributes to the divergence of the behavior experienced in the biological activities tested, but none of the extracts showed a cytotoxic or phototoxic profile in the different tested cell lines. However, the cytoprotective values in front of the H2O2 oxidative stress induced in the 3T3 and HaCaT cell lines position these extracts as possible candidates for future health applications.

The experience of giving birth in a hospital in Spain: Humanization versus technification.

AIM: To explore and describe the experiences of women giving birth in a tertiary public hospital, with special focus on experiences related to humanized care and women's participation in decision making. METHOD: This is a qualitative phenomenological study through semi-structured interviews to postpartum women giving birth in a tertiary hospital between January and May 2017. Data were analysed through content analysis. RESULTS: The two overarching themes emerged were the professional-information dyad and privacy. Subthemes of the first main theme were the therapeutic relationship, decision-making, feeding the baby, procedures, and the time factor. Subthemes of the second topic were the feelings generated by the hospital environment, the delivery room, and the maternity ward. CONCLUSIONS: If the therapeutic relationship is good, technology is not seen as dehumanising but rather as necessary to ensure continuing safety. "Humanising" material resources are not a priority for women in the birth process and are little used. Privacy was experienced as being a particularly intense need, which women called for throughout the healthcare process.

Analgesic effect of inhaled lavender essential oil for frenotomy in healthy neonates: a randomized clinical trial.

BACKGROUND: Neonatal pain may affect long-term neurodevelopment and must be treated. Frenotomy is a painful procedure wherein a common strategy to relieve pain (sucking) cannot be used because the technique is performed on the tongue. Lavender essential oil (LEO) has sedative and antispasmodic properties and has been successfully used to treat pain during heel puncture and vaccination. Our aim was to demonstrate if the use of inhaled LEO is effective in reducing pain during frenotomy in healthy, full-term neonates. METHODS: We conducted a randomized clinical trial in neonates who underwent a frenotomy between August 2020 and April 2021. We assessed pain using pre and post-procedure heart rate and oxygen saturation, crying time and Neonatal Infant Pain Scale (NIPS) score. Patients with type 3 tongue tie were randomized into the "experimental group" and "control group". In both groups, we performed swaddling, administered oral sucrose, and let the newborn suck for two minutes. In the experimental group, we also placed a gauze pad with one drop of LEO under the neonate's nose for two minutes prior to and during the frenotomy. RESULTS: We enrolled 142 patients (71 per group). The experimental group showed significantly lower NIPS scores (1.88 vs 2.92) and cried almost half the amount of time (14.8 vs. 24.6 seconds, P = 0.006). Comparing with the control group, we observed no side effects in either of the groups. CONCLUSIONS: We observed a significant decrease in crying time and lower NIPS scores in the neonates who received inhaled LEO and underwent a frenotomy for type 3 tongue-ties. Thus, we recommend using inhaled LEO during neonatal frenotomies.

Melanogenesis and Hypopigmentation: The Case of Vitiligo.

Melanocytes are highly specialized dendritic cells that synthesize and store melanin in subcellular organelles called melanosomes, before transfer to keratinocytes. Melanin is a complex pigment that provides colour and photoprotection to the skin, hair and eyes. The process of synthesis of melanin is called melanogenesis and is regulated by various mechanisms and factors such as genetic, environmental and endocrine factors. The knowledge of the pigmentation process is important to understand hypopigmentation disorders such as vitiligo and also to design adequate treatments. In the present work, we review the signalling pathways involved in vitiligo. Finally, current therapies and treatments including topical, oral and phototherapies are discussed and described, emphasizing future therapies based on different pigmentation mechanisms.

Polypodium vulgare L. (Polypodiaceae) as a Source of Bioactive Compounds: Polyphenolic Profile, Cytotoxicity and Cytoprotective Properties in Different Cell Lines.

Pteridophytes, represented by ferns and allies, are an important phytogenetic bridge between lower and higher plants. Ferns have evolved independently of any other species in the plant kingdom being its secondary metabolism a reservoir of phytochemicals characteristic of this taxon. The study of the potential uses of Polypodium vulgare L. (Polypodiaceae) as medicinal plant has increased in recent years particularly when in 2008 the European Medicines Agency published a monograph about the rhizome of this species. Our objective is to provide scientific knowledge on the polar constituents extracted from the fronds of P. vulgare, one of the main ferns of European distribution, to contribute to the validation of certain traditional uses. Specifically, we have characterized the methanolic extract of P. vulgare fronds (PVM) by HPLC-DAD and investigated its potential cytotoxicity, phototoxicity, ROS production and protective effects against oxidative stress by using in vitro methods. The 3T3, HaCaT, HeLa, HepG2, MCF-7 and A549 were the cell lines used to evaluate the possible cytotoxic behaviour of the PVM. HPLC-DAD was utilized to validate the polyphenolic profile of the extract. H2O2 and UVA were the prooxidant agents to induce oxidative stress by different conditions in 3T3 and HaCaT cell lines. Antioxidant activity of in vitro PVM in 3T3 and HaCaT cell lines was evaluated by ROS assay. Our results demonstrate that PVM contains significant amounts of shikimic acid together with caffeoylquinic acid derivatives and flavonoids such as epicatechin and catechin; PVM is not cytotoxic at physiological concentrations against the different cell lines, showing cytoprotective and cellular repair activity in 3T3 fibroblast cells. This biological activity could be attributed to the high content of polyphenolic compounds. The fronds of the P. vulgare are a source of polyphenolic compounds, which can be responsible for certain traditional uses like wound healing properties. In the present work, fronds of the common polypody are positioned as a candidate for pharmaceutical applications based on traditional medicine uses but also as potential food ingredients due to lack of toxicity at physiological concentrations.

Multifunctional PLGA nanoparticles combining transferrin-targetability and pH-stimuli sensitivity enhanced doxorubicin intracellular delivery and in vitro antineoplastic activity in MDR tumor cells.

Targeted delivery aims to enhance cellular uptake and improve therapeutic outcome with higher disease specificity. The expression of transferrin receptor (TfR) is upregulated on tumor cells, which make the protein Tf and its receptor vastly relevant when applied to targeting strategies. Here, we proposed Tf-decorated pH-sensitive PLGA nanoparticles containing the chemosensitizer poloxamer as a carrier for doxorubicin delivery to tumor cells (Tf-DOX-PLGA-NPs), aiming at alleviating multidrug resistance (MDR). We performed a range of in vitro studies to assess whether targeted NPs have the ability to improve DOX antitumor potential on resistant NCI/ADR-RES cells. All evaluations of the Tf-decorated NPs were performed comparatively to the nontargeted counterparts, aiming to evidence the real role of NP surface functionalization, along with the benefits of pH-sensitivity and poloxamer, in the improvement of antiproliferative activity and reversal of MDR. Tf-DOX-PLGA-NPs induced higher number of apoptotic events and ROS generation, along with cell cycle arrest. Moreover, they were efficiently internalized by NCI/ADR-RES cells, increasing DOX intracellular accumulation, which supports the greater cell killing ability of these targeted NPs with respect to MDR cells. Altogether, these findings supported the effectiveness of the Tf-surface modification of DOX-PLGA-NPs for an improved antiproliferative activity. Therefore, our pH-responsive Tf-inspired NPs are a promising smart drug delivery system to overcome MDR effect at some extent, enhancing the efficacy of DOX antitumor therapy.

Overcoming MDR by Associating Doxorubicin and pH-Sensitive PLGA Nanoparticles Containing a Novel Organoselenium Compound-An In Vitro Study.

In this study, we developed PLGA nanoparticles (NPs) as an effective carrier for 5'-Se-(phenyl)-3-(amino)-thymidine (ACAT-Se), an organoselenium compound, nucleoside analogue that showed promising antitumor activity in vitro. The PLGA NPs were prepared by the nanoprecipitation method and modified with a pH-responsive lysine-based surfactant (77KL). The ACAT-Se-PLGA-77KL-NPs presented nanometric size (around 120 nm), polydispersity index values < 0.20 and negative zeta potential values. The nanoencapsulation of ACAT-Se increased its antioxidant (DPPH and ABTS assays) and antitumor activity in MCF-7 tumor cells. Hemolysis study indicated that ACAT-Se-PLGA-77KL-NPs are hemocompatible and that 77KL provided a pH-sensitive membranolytic behavior to the NPs. The NPs did not induce cytotoxic effects on the nontumor cell line 3T3, suggesting its selectivity for the tumor cells. Moreover, the in vitro antiproliferative activity of NPs was evaluated in association with the antitumor drug doxorubicin. This combination result in synergistic effect in sensitive (MCF-7) and resistant (NCI/ADR-RES) tumor cells, being especially able to successfully sensitize the MDR cells. The obtained results suggested that the proposed ACAT-Se-loaded NPs are a promising delivery system for cancer therapy, especially associated with doxorubicin.

UVB photoprotective capacity of hydrogels containing dihydromyricetin nanocapsules to UV-induced DNA damage.

We evaluate the effect of cationic nanocapsules containing dihydromyricetin (DMY) flavonoid for safe topical use in photoprotection against UV-induced DNA damage. The stability was investigated for feasibility to produce hydrogels containing cationic nanocapsules of the flavonoid DMY (NC-DMY) for 90 days under three different storage conditions (4 ± 2 °C, 25 ± 2 °C, and 40 ± 2 °C), as well as evaluation of skin permeation and its cytotoxicity in skin cell lines. The physicochemical and rheological characteristics were maintained during the analysis period under the different aforementioned conditions. However, at 25 °C and 40 °C, the formulations indicated yellowish coloration and DMY content reduction. Therefore, the ideal storage condition of 4 °C was adopted. DMY remained in the stratum corneum and the uppermost layers of the skin. Regarding safety, all formulations demonstrated to be safe for topical application. NC-DMY exhibited a 50% Solar Protection Factor (SPF-DNA) against DNA damage caused by UVB radiation and demonstrated 99.9% protection against DNA lesion induction. These findings establish a promising formulation containing nanoencapsulated DMY flavonoids with a photoprotective and antioxidant potential of eliminating reactive oxygen species formed by solar radiation.

Is there a significant decrease in the femoral cortical bone around Furlong® stems after 18 years of follow-up?

INTRODUCTION: In the context of total hip arthroplasty (THA), there are several reasons that have motivated the development of short stems. It has been postulated that short stems allow a better conservation of the bone stock if compared to conventional stems. As far as we have knowledge, the quantitative loss of diaphyseal bone stock in patients with standard femoral stems has not been fully described. The aim of this study was to provide evidences about the thickness of the cortical bone at the diaphysis in patients who have undergone unilateral THA with Furlong® stems with a minimum follow-up of 18 years. PATIENTS AND METHODS: A retrospective study of patients who underwent THA in a single hospital was performed. The inclusion criteria were patients who had undergone a non-cemented elective THA with a Furlong® stem, minimum follow-up of 18 years, and contralateral femur and hip without history of previous surgical procedures. The follow-up analysis was performed by means of radiological examinations performed at the last follow-up visit. Data related to the sex, age at surgery and adverse events registered during the follow-up were gathered. The cortical thickness index (CTI) and cortical thickness (CT) assessed at the last follow-up visit in anteroposterior pelvic X-rays were analyzed, both in the operated hip and in the non-operated hip (which was used as control). Calibration of the measurements was done by means of using the circumference of the head of the THA. RESULTS: The total number of patients who met the inclusion criteria was 22. There were 14 women and eight men. There were 12 left hips. The mean age at the time of surgery was 59.32 ± 6.83 (range 50-70) years. The mean follow-up was 20.86 ± 1.90 (range 18-24) years. The CTI was found to be 11.93% greater in the non-operated hips. The CT measured at 3 cm and 6 cm from lesser trochanter, and at 9 cm from the greater trochanter, was found to be 21.64%, 15.33% and 18.73% greater in the non-operated hips, respectively. CONCLUSION: After a minimum of 18 years from the implantation of a Furlong® stem, the bone density that surrounds the implant seems to involve a cortical bone ten percent less thick than the cortical bone of the non-operated contralateral side. With this stem, the cortical zones with less CT seem to be the lateral cortex at 9 cm from the greater trochanter, and the medial cortex at 3 and 6 cm from the lesser trochanter. LEVEL OF EVIDENCE: III, retrospective case-control study.

Protective effect of guarana-loaded liposomes on hemolytic activity.

Paullinia cupana var. sorbilis (Mart.) Ducke, popularly known as guarana, is one of the most promising plants in Brazilian flora and has attracted considerable interest from the scientific community owing to its numerous therapeutic activities and less side effects. Hence, using nanotechnology is a viable alternative to primarily improve the physicochemical characteristics and bioavailability of guarana. The objective of the present study was to develop, characterize, and evaluate the stability of liposomes containing guarana powder and to evaluate their antioxidant and hemolytic activity in vitro. Three different concentrations of guarana powder and two methods of liposome preparation were tested. Liposomes were developed and characterized, and their stability was analyzed by evaluating physicochemical parameters. Hemolytic activity of guarana liposomal formulation (G-Lip) was compared with that of guarana in its free form (FG) and of liposome without guarana (W-Lip). Red blood cells from rats were exposed to these different formulations dissolved in phosphate buffer solution (PBS; pH 7.4). The best stability was achieved for the formulation containing 1 mg mL-1 guarana powder produced by the reverse phase evaporation method. FG showed dose-dependent antioxidant activity, which was maintained in G-Lip. W-Lip showed high hemolytic activity in PBS at pH 7.4 possibly because of the presence of polysorbate 80, and on addition of guarana to these structures, the hemolytic process was reversed. The same protective effect was observed for FG. It is believed that the complex structure of guarana, primarily the presence of polyphenols, exerts a powerful antioxidant action, helping to protect erythrocytes.

MKC-Quatsomes: a stable nanovesicle platform for bio-imaging and drug-delivery applications.

Quatsomes are outstanding new lipid-based nanovesicles that are highly homogeneous and stable in different media for years, but the composition must be carefully chosen to avoid any potentially toxic side effects in in vivo applications. To this end, we have developed and studied a novel type of Quatsomes composed of cholesterol and myristalkonium chloride (MKC), the latter being extensively used as antimicrobial preservative in many ophthalmic and parenteral formulations on the EU and USA market. We have synthesized these novel MKC-Quatsomes in different media that are suitable for parenteral administration, and confirmed their stability in these media for 18 months, as well as the stability in human serum for 24 hours. Biodistribution assays were performed after intravenous injection of fluorescently labeled MKC-Quatsomes in live mice bearing xenografted colorectal tumors, showing nanovesicle accumulation in tumors, liver, spleen, and kidneys. No histological alteration or toxicity was observed in any of these organs.

Comparative evaluation of the hepatotoxicity, phototoxicity and photosensitizing potential of dronedarone hydrochloride and its cyclodextrin-based inclusion complexes.

In this study, the hepatotoxicity, phototoxicity and photosensitizing potential of free dronedarone (DRO) and its inclusion complexes with ß-cyclodextrin (ß-CD) and 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD), prepared by different methods, were investigated by using in vitro cell-based approaches. The results of the 3T3 NRU phototoxicity assay showed that free DRO and the CD-based inclusion complexes did not present any substantial phototoxic potential. The photosensitizing potential was assessed by using THP-1 cells and IL-8 as a biomarker, and the experimental data confirmed that both the free drug and the inclusion complexes are likely to cause skin photosensitization, as they were able to induce IL-8 release after irradiation. Nevertheless, the inclusion complexes obtained by kneading followed by spray-drying induced a lower IL-8 release and also presented a smaller stimulation index in comparison with free DRO, suggesting a reduction in the photosensitizing potential. Finally, the free drug and inclusion complexes were also tested for hepatotoxicity using HepG2 cells. Even though lower IC50 values were found for the inclusion complexes prepared by kneading followed by spray-drying, there was no significant difference, indicating that the complexation of dronedarone did not induce hepatotoxicity. Overall, the obtained data confirmed that the inclusion complexes prepared by kneading followed by spray-drying, especially those based on HP-ß-CD, appeared to be the most promising formulations and, therefore, could be encouragingly explored in the development of novel pharmaceutical dosage forms containing DRO, presumably with reduced side effects and improved safety profile.

Preparation, characterization and in vitro cytotoxicity study of dronedarone hydrochloride inclusion complexes.

Dronedarone is a new antiarrhythmic drug for the treatment of atrial fibrillation. This study investigated the complexation of dronedarone hydrochloride with ß­cyclodextrin (ß-CD) and 2­hydroxypropil­ß­CD (HP-ß-CD) using three different techniques. The complexes in the solid state were characterized by DSC, TGA, PXRD, FT-IR, SEM and 1H NMR, demonstrating the formation of the inclusion complexes and exhibiting different properties from the pure drug. Its aqueous solubility increased about 4.0-fold upon complexation with ß-CD and HP-ß-CD. The dissolution rate of the drug was notably improved in all tested physiological pH values from 1.2 to 6.8 in the presence of both cyclodextrins. Furthermore, an in vitro cytotoxic assay revealed that the inclusion complexes could reduce the cytotoxic effects of the drug on 3T3 cells. The overall results suggest that the inclusion complexes with ß-CD and HP-ß-CD may be potentially useful in the preparation of novel pharmaceutical formulations containing dronedarone hydrochloride.

Lignins and Their Derivatives with Beneficial Effects on Human Health.

A review of the pharmacological applications of lignins provides evidence of their protective role against the development of different diseases. In many cases, the effects of lignins could be explained by their antioxidant capacity. Here, we present a systematic review of the literature from the period 2010-2016 which provides information concerning new applications of lignins derived from recent research. The most promising findings are reported, including the methodologies employed and results obtained with lignins or their derivatives which may improve human health. We highlight potential applications in the treatment of obesity, diabetes, thrombosis, viral infections and cancer. Moreover, we report both that lignins can be used in the preparation of nanoparticles to deliver different drugs and also their use in photoprotection.

In Vitro Comparative Skin Irritation Induced by Nano and Non-Nano Zinc Oxide.

This study was designed to determine whether nano-sized ZnO has the potential to cause acute cutaneous irritation using cultured HaCaT keratinocytes and a human skin equivalent as in vitro models, compared to non-nanomaterials. Commercial nano ZnO with different sizes (50 nm and 100 nm) was characterized by dynamic light scattering (DLS) and microscopy (SEM) in different media. Nano ZnO reduced the cell viability of HaCaT in a dose-dependent and time-dependent manner, in a similar way to macro ZnO. However, the 3D-epidermis model revealed no irritation at 1 mg/mL after 24 h of exposure. In conclusion, nano-sized ZnO does not irritate skin, in a similar manner to non-nano ZnO.

Chitosan-tripolyphosphate nanoparticles functionalized with a pH-responsive amphiphile improved the in vitro antineoplastic effects of doxorubicin.

Delivery systems with pH-responsiveness behavior are of particular interest because they could allow exploring the various pH gradients within the body, for example, between healthy tissue and tumor tissue, or between extracellular tissue and some cell compartments. Likewise, modifications in nanocarriers with polyethylene glycol (PEG) and poloxamer could be a potential approach to improve the effectiveness of cancer treatments. On these premises, we prepared pH-responsive DOX-loaded chitosan-tripolyphosphate nanoparticles (NPs), modified or not with PEG or poloxamer, and incorporating an anionic dyacyl lysine-based surfactant with sodium counterion (77KS) as a pH-sensitive adjuvant. Owing to its pH-sensitivity, the CS-NPs showed membranolytic behavior upon reducing the pH value of surrounding media to 6.6 and 5.4, which are characteristic of the endosomal compartments. The in vitro antiproliferative assays with MCF-7 and HeLa tumor cells indicated that the NPs themselves had no associated significant cytotoxicity, while DOX-loaded NPs induced higher cytotoxicity than free drug. Additionally, DOX-loaded CS-NPs displayed greater selectivity to tumor cells than to the non-tumor 3T3 fibroblasts. The feasibility of using these NPs to target tumor microenvironment was proven, as cytotoxicity against cancer cell models was higher in a mildly acidic environment. Finally, the hemocompatibility of NPs was demonstrated, indicating their suitability for intravenous administration. Altogether, the results suggest that the combination of endosomal acidity with the potential endosomolytic capability of these pH-responsive nanocarriers could increase the intracellular delivery of DOX and, thus, might enhance its antineoplastic efficacy.

Antioxidant comparative effects of two grape pomace Mexican extracts from vineyards on erythrocytes.

Maceration and Soxhlet methods were used to obtain methanol extracts from a Mexican grape (Ruby Cabernet) pomace and the biological activity and phenolic profiles were compared. The antioxidant capacity was used to evaluate the mechanism of action, using a physiological model (erythrocytes) of damage induced by AAPH-generated free radicals. The extract obtained by maceration presented a total phenolic content twice the one obtained using the Soxhlet method. It also contained the most potent antioxidants, reducing anisotropy in the presence of AAPH to the levels of untreated cells, restoring membrane fluidity, preventing the morphological changes, as demonstrated by scanning electron microscopy (SEM), and providing protection against protein oxidation at the higher concentration. Our work showed that both extracts presented significant antioxidant activity through positive interactions with the lipid bilayer.