Ceftazidime and Usnic Acid Encapsulated in Chitosan-Coated Liposomes for Oral Administration against Colorectal Cancer-Inducing Escherichia coli.

Escherichia coli has been associated with the induction of colorectal cancer (CRC). Thus, combined therapy incorporating usnic acid (UA) and antibiotics such as ceftazidime (CAZ), co-encapsulated in liposomes, could be an alternative. Coating the liposomes with chitosan (Chi) could facilitate the oral administration of this nanocarrier. Liposomes were prepared using the lipid film hydration method, followed by sonication and chitosan coating via the drip technique. Characterization included particle size, polydispersity index, zeta potential, pH, encapsulation efficiency, and physicochemical analyses. The minimum inhibitory concentration and minimum bactericidal concentration were determined against E. coli ATCC 25922, NCTC 13846, and H10407 using the microdilution method. Antibiofilm assays were conducted using the crystal violet method. The liposomes exhibited sizes ranging from 116.5 ± 5.3 to 240.3 ± 3.5 nm and zeta potentials between +16.4 ± 0.6 and +28 ± 0.8 mV. The encapsulation efficiencies were 51.5 ± 0.2% for CAZ and 99.94 ± 0.1% for UA. Lipo-CAZ-Chi and Lipo-UA-Chi exhibited antibacterial activity, inhibited biofilm formation, and preformed biofilms of E. coli. The Lipo-CAZ-UA-Chi and Lipo-CAZ-Chi + Lipo-UA-Chi formulations showed enhanced activities, potentially due to co-encapsulation or combination effects. These findings suggest potential for in vivo oral administration in future antibacterial and antibiofilm therapies against CRC-inducing bacteria.

Bee Venom Toxic Effect on MDA-MB-231 Breast Cancer Cells and Caenorhabditis Elegans.

INTRODUCTION: Bee venom has therapeutics and pharmacological properties. Further toxicological studies on animal models are necessary due to the severe allergic reactions caused by this product. METHOD: Here, Caenorhabditis elegans was used as an in vivo toxicity model, while breast cancer cells were used to evaluate the pharmacological benefits. The bee venom utilized in this research was collected from Apis mellifera species found in Northeast Brazil. The cytotoxicity caused by bee venom was measured by MTT assay on MDA-MB-231 and J774 A.1 cells during 24 - 72 hours of exposure. C. elegans at the L4 larval stage were exposed for three hours to M9 buffer or bee venom. Survival, behavioral parameters, reproduction, DAF-16 transcription factor translocation, the expression of superoxide dismutase (SOD), and metabolomics were analyzed. Bee venom suppressed the growth of MDA-MB-231 cancer cells and exhibited cytotoxic effects on macrophages. Also, decreased C. elegans survival impacted its behaviors by decreasing C. elegans feeding behavior, movement, and reproduction. RESULTS: Bee venom did not increase the expression of SOD-3, but it enhanced DAF-16 translocation from the cytoplasm to the nucleus. C. elegans metabolites differed after bee venom exposure, primarily related to aminoacyl- tRNA biosynthesis, glycine, serine and threonine metabolism, and sphingolipid and purine metabolic pathways. Our findings indicate that exposure to bee venom resulted in harmful effects on the cells and animal models examined. CONCLUSION: Thus, due to its potential toxic effect and induction of allergic reactions, using bee venom as a therapeutic approach has been limited. The development of controlled-release drug strategies to improve this natural product's efficacy and safety should be intensified.

Isothermal titration calorimetry (ITC) as a promising tool in pharmaceutical nanotechnology.

Isothermal titration calorimetry (ITC) is a technique for evaluating the thermodynamic profiles of connection between two molecules, allowing the experimental design of nanoparticles systems with drugs and/or biological molecules. Taking into account the relevance of ITC, we conducted, therefore, an integrative revision of the literature, from 2000 to 2023, on the main purposes of using this technique in pharmaceutical nanotechnology. The search were carried out in the Pubmed, Sciencedirect, Web of Science, and Scifinder databases using the descriptors "Nanoparticles", "Isothermal Titration Calorimetry", and "ITC". We have observed that the ITC technique has been increasingly used in pharmaceutical nanotechnology, seeking to understand the interaction mechanisms in the formation of nanoparticles. Additionally, to understand the behavior of nanoparticles with biological materials (proteins, DNA, cell membranes, among others), thereby helping to understand the behavior of nanocarriers in vivo studies. As a contribution, we intended to reveal the importance of ITC in the laboratory routine, which is itself a quick and easy technique to obtain relevant results that help to optimize the nanosystems formulation process.

Assessment of Cytotoxic/Antitumour Potential and in silico Study of Salazinic Acid Isolated from Parmotrema concurrens.

INTRODUCTION: Despite numerous scientific advances, cancer continues to be one of the main causes of death in the world. This situation has driven the search for promising molecules. Lichen substances have been widely described for their pharmacological potential. OBJECTIVE: The present study evaluated the antitumour potential of a depsidone isolated from Parmotrema concurrens- salazinic acid (SAL) - through in vitro, in vivo and in silico studies. METHODS: The molecule was isolated from the acetonic extract of the lichen and recrystallized in acetone. The macrophage J774, sarcoma-180 and MDA-MB-231 cell lines were used for the MTT cytotoxicity assay. The antitumor assay used a murine model (Swiss albino mice) with sarcoma-180. The animals were treated for seven consecutive days with doses of SAL (25 and 50 mg/kg) and 5-fluorouracil (20 mg/kg). RESULTS: Its purity was determined using high-performance liquid chromatography (94%), and its structure was confirmed by H1 and C13 nuclear magnetic resonance. SAL was not considered toxic to cancer cell lines, showing cell viability rates of 79.49 ± 4.15% and 86.88 ± 1.02% for sarcoma-180 and MDA-MB-231, respectively. The tumour inhibition rate was greater than 80% in the animals treated with SAL and 65% for those that received 5-fluorouracil. Simulations of molecular dynamics to estimate the flexibility of the interactions between human thymidylate synthase and derivatives of SAL and 5-fluorouracil revealed that SAL exhibited greater enzymatic interaction capacity, with highly favourable energy, compared to 5-fluorouracil. CONCLUSION: The present results demonstrate the potential of salazinic acid as a tumour inhibition agent.

Protective mucus effect of the crude fraction of the mucus produced by the zoanthide Palythoa caribaeorum.

AIMS: This study aimed to evaluate the gastroduodenal protective action of crude fraction extracted from P. caribaeorum mucus in Wistar rats. MAIN METHOD: Initially, phytochemical screening was performed to measure secondary metabolites present in the extract. Subsequently, studies of gastroprotective action in Wistar rats were developed. The animals were randomly divided into six experimental groups: SF0.9% group, misoprostol group, and test groups (200, 100, 10, and 1 mg/kg) that received different doses of the crude fraction of zoanthid mucus (CFZM) diluted in SF0.9%. After 14 days of treatment, acute gastric ulcers were induced by gavage by administering aspirin (200 mg/kg). The stomach and duodenum were removed for histopathological and gene analysis of the mucosa. KEY FINDINGS: The present study found that all investigated metabolites showed negative results. The crude fraction showed a gastric and duodenal protective effect evidenced by an increase in the amount and production of mucins (MUC1 and MUC5AC) and mucus production area in the stomach. Histopathological analysis evidenced a decrease in epithelial damage in the duodenum, with a more significant extension of intestinal villi and a greater amount of goblet cells. SIGNIFICANCE: The crude fraction, extracted from P. caribaeorum, showed gastric and duodenal protective action and is not inert in murine gastroduodenal tissues.

Nanotechnology and tuberculosis: An old disease with new treatment strategies.

Tuberculosis is an intracellular infectious disease caused by Mycobacterium tuberculosis, which mainly affects the lungs. Especially in patients infected by the Human Immunodeficiency Virus (HIV) or other immunosuppressed patients, tuberculosis is considered one of the infectious diseases with higher morbidity and mortality rates. Despite considerable improvements in diagnosis and treatment during the last decades, the drugs currently used in tuberculosis treatment still have limitations, such as low plasma levels after oral administration, low solubility in water, fast metabolization by the liver with a short 1/2 life and low patient adherence to treatment. Another limiting point is drug-resistant strains. Thus, to overcome such limitations, nanotechnology emerges as a promising alternative due to the drug release systems and its recent advances that show potential improvements, such as improved bioavailability and reduction of the therapeutic dose. In this context, this manuscript aimed to highlight the nanotechnology-based drug delivery systems studies pointing to those most effective for tuberculosis treatment. Studies based on polymeric nanoparticles are promising in diagnosing, treating, and even preventing tuberculosis because they have the high stability and transport capacity of these drugs. Solid lipid nanoparticles are another type of promising nanocarriers for treating tuberculosis, mainly for delivering drugs to the remote lymphatic system. Other promising nanosystems are the liposomes, since they have also shown efficacy in significantly reducing bacterial load compared to conventional drug administration. Given the results presented, the administration of drugs through nanotechnology-based drug delivery systems has benefits in treating tuberculosis since in vitro and in vivo studies have revealed that nanotechnology through nano- and micro-scale systems is an effective and promising approach for the treatment of tuberculosis. Furthermore, the increase in the number of patents for nanosystems aimed at treating TB has demonstrated researchers' commitment in the quest to improve the therapeutic arsenal against tuberculosis.

Quality of life in women with breast cancer treated at a radiotherapy centre in Caruaru, Pernambuco, Brazil.

Objective: To evaluate the quality of life (QOL) of patients with breast cancer undergoing radiotherapy treatment. Methods: The current study is a descriptive quantitative approach that seeks to identify the QOL of breast cancer patients during their radiotherapy treatment. A convenience sample of 30 women undergoing radiotherapy for breast cancer completed the EORTC QLQC30 questionnaire on Day 1 and Day 28. Results: Results showed significant differences in QOL between the two sessions. Decreases in overall health (88.33 to 61.67) and functional health (76.45 to 67.77) were noted in parallel to an increase in the scale of symptoms (13.85 for 24.62). Conclusions: The radiotherapeutic treatment impacts the QOL of patients with breast cancer. It is crucial for the nursing team to work together with a multi-professional team to adequately manage the treatment of these patients adequately.

Does Oncocalyxone A (oncoA) have intrinsic fluorescence?

BACKGROUND: Oncocalyxone A (oncoA) is a quinone extracted from the Cordia oncocalyx plant. This compound has pharmacological properties, such as anti-inflammatory, analgesic, and cytotoxic activities, among others. OncoA presents a similar chemical structure to doxorubicin, a drug used in cancer treatment, which possesses an intrinsic fluorescence explored in various studies, including those using doxorubicin-loaded nanoparticles. Thus, due to the chemical structural similarity, the question arose whether oncoA could also show autofluorescence. Therefore, this study proposed to characterize the absorption and emission spectral profiles of oncoA and analyze if this compound could be used as a fluorescent probe. METHODS: For this, fucoidan-coated polyisobutylcyanoacrylate (PIBCA) nanoparticles containing oncoA were prepared, and an uptake study was performed using a human metastatic breast cancer cell line (MDA-MB-231 cells). RESULTS: OncoA presented a maximum emission wavelength in the blue region, near 430 nm, at 350 nm excitation, compatible with standard microscope optics. Fluorescence microscopy analyses showed that oncoA-loaded PIBCA nanoparticles were internalized by MDA-MB-231 cells under incubation times as shorter as 15 min. CONCLUSION: According to these findings, oncoA-encapsulated nanoparticles are promising fluorescent probes and could be useful for cellular uptake studies.

Nanotechnology and COVID-19: quo vadis?

The pandemic COVID-19 has worried everyone due to the high mortality rate and the high number of people hospitalized with severe acute respiratory syndrome caused by SARS-CoV-2. Given the seriousness of this disease, several companies and research institutions have sought alternative treatment and/or prevention methods for COVID-19. Due to its versatility, nanotechnology has allowed the development of protective equipment and vaccines to prevent the disease and reduce the number of severe COVID-19 cases. Thus, this article combined the main works and products developed in a nanotechnological field for COVID-19. We performed a literature search using the keywords "COVID-19," "SARS-CoV-2," "nanoparticles," "nanotechnology," and "liposomes" in the SciELO, Scifinder, PubMed, Sciencedirect, ClinicalTrials, and Nanotechnology Products databases Database. The data survey indicated 48 articles, 62 products, and 32 patents. The use of nanotechnology against COVID-19 has brought benefits in several parameters of this disease, helping develop rapid diagnostic tests that release the result in 10 min, as well as developing vaccines containing genetic material from SARS-CoV-2 (DNA, mRNA, and protein subunits). Nanotechnology is an exceptional ally against COVID-19, contributing to the most diverse areas, helping both prevent, diagnose, and treat COVID-19.

Immobilization of fibrinolytic protease from Mucor subtilissimus UCP 1262 in magnetic nanoparticles.

This work reports the immobilization of a fibrinolytic protease (FP) from Mucor subtilissimus UCP 1262 on Fe3O4 magnetic nanoparticles (MNPs) produced by precipitation of FeCl3·6H2O and FeCl2·4H2O, coated with polyaniline and activated with glutaraldehyde. The FP was obtained by solid state fermentation, precipitated with 40-60% ammonium sulfate, and purified by DEAE-Sephadex A50 ion exchange chromatography. The FP immobilization procedure allowed for an enzyme retention of 52.13%. The fibrinolytic protease immobilized on magnetic nanoparticles (MNPs/FP) maintained more than 60% of activity at a temperature of 40 to 60 °C and at pH 7 to 10, when compared to the non-immobilized enzyme. MNPs and MNPs/FP did not show any cytotoxicity against HEK-293 and J774A.1 cells. MNPs/FP was not hemolytic and reduced the hemolysis induced by MNPs from 2.07% to 1.37%. Thrombus degradation by MNPs/FP demonstrated that the immobilization process guaranteed the thrombolytic activity of the enzyme. MNPs/FP showed a total degradation of the γ chain of human fibrinogen within 90 min. These results suggest that MNPs/FP may be used as an alternative strategy to treat cardiovascular diseases with a targeted release through an external magnetic field.

ConA-Coated Liposomes as a System to Delivery ß-Lapachone to Breast Cancer Cells.

BACKGROUND: Target treatment using site-specific nanosystems is a hot topic for treating several diseases, especially cancer. OBJECTIVE: The study was set out to develop site-specific liposomes using ConcanavalinA (ConA) to target ß- lapachone(ß-lap) to human breast cancer cells. METHODS: Liposomes were prepared and characterized according to diameter size, zeta potential, ConA conjugation(%) and ß-lap encapsulation efficiency (%). Isothermal Titration Calorimetry evaluated the binding energy between the biomolecules, which compose of the liposomes. ConA avidity was assessed before and after conjugation. Cytotoxicity was evaluated, and fluorescence microscopy was performed to investigate the influence of ConA influenced on MCF-7 uptake. RESULTS: Uncoated and ConA-coated liposomes presented size, and zeta potential values from 97.46 ± 2.01 to 152.23 ± 2.73 nm, and -6.83 ± 0.28 to -17.23 ±0.64 mV, respectively. Both ConA conjugation and ß-lap encapsulation efficiency were approximately 100%. The favorable and spontaneous process confirmed the binding between ConA and the lipid. Hemagglutination assay confirmed ConA avidity once Lipo-ConA and Lipo-PEG-ConA were able to hemagglutinate the red blood cells at 128-1 and 256-1, respectively. Lipo-ConA was not cytotoxic, and the site-specific liposomes presented the highest toxicity. ConA-coated liposomes were more internalized by MCF7 than uncoated-liposomes. CONCLUSION: Therefore, the presence of ConA on the surface of liposomes influenced MCF7 uptake, in that way could be used as a promising site-specific system to target ß-lap to cancer cells.

Fucoidan-Coated Liposomes: A Target System to Deliver the Antimicrobial Drug Usnic Acid to Macrophages Infected with Mycobacterium tuberculosis.

The present study describes the use of fucoidan, a negative sulfated polysaccharide, as a coating material for the development of liposomes targeted to macrophages infected with Mycobacterium tuberculosis. First, fucoidan was chemically modified to obtain a hydrophobized-fucoidan derivative (cholesteryl-fucoidan) using a two-step microwave-assisted (µW) method. The total reaction time was decreased from 14 hours to 1 hour while maintaining the overall yield. Cholesterylfucoidan was then used to prepare surface-modified liposomes containing usnic acid (UA-LipoFuc), an antimicrobial lichen derivative. UA-LipoFuc was evaluated for mean particle size, polydispersity index (PDI), surface charge (ζ), and UA encapsulation efficiency. In addition, a cytotoxicity study, competition assay and an evaluation of antimycobacterial activity against macrophages infected with M. tuberculosis (H37Ra) were performed. When the amount of fucoidan was increased (from 5 to 20 mg), vesicle size increased (from 168 ± 2.82 nm to 1.18 ± 0.01 µm). Changes in from +20 ± 0.41 mV for uncoated liposomes to -5.41 ± 0.23 mV for UA-LipoFuc suggested that the fucoidan was placed on the surface of the liposomes. UA-LipoFuc exhibited a lower IC50 (8.26 ± 1.11 µM) than uncoated liposomes (18.37 ± 3.34 µM), probably due to its higher uptake. UA-LipoFuc5 was internalized through the C-type carbohydrate recognition domain of the cell membrane. Finally, usnic acid, both in its free form and encapsulated in fucoidan-coated liposomes (UA-LipoFuc5), was effective against infected macrophages. Hence, this preliminary investigation suggests that encapsulated usnic acid will aid in further studies related to infected macrophages and may be a potential option for tuberculosis treatment.

Silver nanoprisms as plasmonic enhancers applied in the photodynamic inactivation of Staphylococcus aureus isolated from bubaline mastitis.

Mastitis is a bacterial infection that affects all lactating mammals, and in dairy cattle, it leads to a reduction in their milk production and, in worse cases, it may lead to animal death. One viable therapeutic modality for overcoming bacterial resistance can be photodynamic inactivation (PDI), a therapeutic modality for bacterial infection treatment. One of the main factors that can lead to an efficient PDI process is the association of metallic nanoparticles in the close vicinity of photosensitizers, which has shown promising results due to localized surface plasmon resonance phenomena. In this work, methylene blue (MB) molecules were associated with Ag prismatic nanoplatelets (AgNPrs) to use as PDI photosensitizer against Staphylococcus aureus isolated from bubaline mastitis. The optical plasmonic activity of AgNPrs was tuned to the MB absorption region (600-700 nm) by inducing their growth into prismatic shapes by a seed-mediated procedure, using poly (sodium 4-styrene sulfonate) as the surfactant. A simulation on the plasmonic properties of the nanoprisms, applying particle size within the dimensions determined by TEM image analysis (d = 32 ± 6 nm), showed a 30 % increase of the incident field on the prismatic tips. Photodynamic results showed that the electrostatic AgNPr-MB conjugates promoted enhancement (ca. 15 %) of the reactive oxygen species production. Besides, PDI mediated by AgNPrs-MB led to the complete inactivation of the mastitis S. aureus strain after 6 min inactivation, in contrast to PDI mediated by MB, which reduced less than a 0.5 bacterial log. Thus, the results show this plasmonic enhanced photodynamic tool's potential to be applied in the inactivation of multi-resistant bacterial strains.

Levobupivacaine-Loaded Liposome Associated with Thermogel for Prolonged Analgesia.

Pain is a phenomenon present in the majority of the population, affecting, among others, the elderly, overweight people, and especially recently operated patients, analgesia being necessary. In the specific case of relief of postoperative pain, different kinds of anesthetics are being used, among them bupivacaine, a widely used drug which promotes long-lasting analgesic effects. However, cardiotoxicity and neurotoxicity are related to its repetitive use. To overcome these shortcomings, Novabupi® (a racemic mixture) was developed and is marketed as an injectable solution. This formulation contains an enantiomeric excess of the levogyre isomer, which has reduced toxicity effects. Seeking to rationalize its use by extending the duration of effect and reducing the number of applications, the objectives of this work were to develop and evaluate liposomes containing Novabupi (LBPV), followed by incorporation into thermogel. Liposomes were prepared using the lipid hydration method, followed by size reduction using sonication, and the developed formulations were characterized by hydrodynamic diameter, polydispersity index (PDI), surface zeta potential, and encapsulation efficiency. The selected optimal liposomal formulation was successfully incorporated into a thermogel without loss of thermoresponsive properties, being suitable for administration as a subcutaneous injection. In the ex vivo permeation studies with fresh rodent skin, the thermogel with liposomes loaded with 0.5% LBPV (T-gel formulation 3) showed higher permeation rates compared to the starting formulation, thermogel with 0.5% LBPV (T-Gel 1), which will probably translate into better therapeutic benefits for treatment of postoperative analgesia, especially with regard to the number of doses applied.

Nanocarriers in the Delivery of Hydroxychloroquine to the Respiratory System: An Alternative to COVID-19.

In response to the global outbreak caused by SARS-CoV-2, this article aims to propose the development of nanosystems for the delivery of hydroxychloroquine in the respiratory system to the treatment of COVID-19. A descriptive literature review was conducted, using the descriptors "COVID-19", "Nanotechnology", "Respiratory Syndrome" and "Hydroxychloroquine", in the PubMed, ScienceDirect and SciElo databases. After analyzing the articles according to the inclusion and exclusion criteria, they were divided into 3 sessions: Coronavirus: definitions, classifications and epidemiology, pharmacological aspects of hydroxychloroquine and pharmaceutical nanotechnology in targeting of drugs. We used 131 articles published until July 18, 2020. Hydroxychloroquine seems to promote a reduction in viral load, in vivo studies, preventing the entry of SARS-CoV-2 into lung cells, and the safety of its administration is questioned due to the toxic effects that it can develop, such as retinopathy, hypoglycemia and even cardiotoxicity. Nanosystems for the delivery of drugs in the respiratory system may be a viable alternative for the administration of hydroxychloroquine, which may enhance the therapeutic effect of the drug with a consequent decrease in its toxicity, providing greater safety for implementation in the clinic in the treatment of COVID-19.

Pharmaceutical nanotechnology: which products are been designed against COVID-19?

The current pandemic COVID-19, caused by the SARS-CoV-2 virus, has been affecting thousands of people worldwide, promoting high numbers of deaths. With this, the world population is going through a process of changing habits, with social distance, improvement of hygiene techniques, to reduce the spread of the SARS-CoV-2 virus and, consequently, reduce the number of hospitalized people in serious condition, as well as the mortality rate. This scenario has been promoting a continuous search for researchers, in the most varied areas, for possible methods of prevention or cure. Specifically, in the field of pharmaceutical nanotechnology, a variety of products are being developed against SARS-CoV-2. Under these circumstances, we propose here an exposition of some of the nanotechnological products (nanoscale between 1 to 1000 nm) currently designed for the detection of the virus, for the prevention and treatment of COVID-19, in addition to equipment for personal protection. We believe that pharmaceutical nanotechnology will be a valuable tool in the disease from the development of products that guarantee our protection against the SARS-CoV-2 virus.

Effects of the encapsulation of usnic acid into liposomes and interactions with antituberculous agents against multidrug-resistant tuberculosis clinical isolates.

Mycobacterium tuberculosis (Mtb) has acquired resistance and consequently the antibiotic therapeutic options available against this microorganism are limited. In this scenario, the use of usnic acid (UA), a natural compound, encapsulated into liposomes is proposed as a new approach in multidrug-resistant tuberculosis (MDR-TB) therapy. Thus the aim of this study was to evaluate the effect of the encapsulation of UA into liposomes, as well as its combination with antituberculous agents such as rifampicin (RIF) and isoniazid (INH) against MDR-TB clinical isolates. The in vitro antimycobacterial activity of UA-loaded liposomes (UA-Lipo) against MDR-TB was assessed by the microdilution method. The in vitro interaction of UA with antituberculous agents was carried out using checkerboard method. Minimal inhibitory concentration values were 31.25 and 0.98 µg/mL for UA and UA-Lipo, respectively. The results exhibited a synergistic interaction between RIF and UA [fractional inhibitory concentration index (FICI) = 0.31] or UA-Lipo (FICI = 0.28). Regarding INH, the combination of UA or UA-Lipo revealed no marked effect (FICI = 1.30-2.50). The UA-Lipo may be used as a dosage form to improve the antimycobacterial activity of RIF, a first-line drug for the treatment of infections caused by Mtb.

Effects of the encapsulation of usnic acid into liposomes and interactions with antituberculous agents against multidrug-resistant tuberculosis clinical isolates

Mycobacterium tuberculosis (Mtb) has acquired resistance and consequently the antibiotic therapeutic options available against this microorganism are limited. In this scenario, the use of usnic acid (UA), a natural compound, encapsulated into liposomes is proposed as a new approach in multidrug-resistant tuberculosis (MDR-TB) therapy. Thus the aim of this study was to evaluate the effect of the encapsulation of UA into liposomes, as well as its combination with antituberculous agents such as rifampicin (RIF) and isoniazid (INH) against MDR-TB clinical isolates. The in vitro antimycobacterial activity of UA-loaded liposomes (UA-Lipo) against MDR-TB was assessed by the microdilution method. The in vitro interaction of UA with antituberculous agents was carried out using checkerboard method. Minimal inhibitory concentration values were 31.25 and 0.98 µg/mL for UA and UA-Lipo, respectively. The results exhibited a synergistic interaction between RIF and UA [fractional inhibitory concentration index (FICI) = 0.31] or UA-Lipo (FICI = 0.28). Regarding INH, the combination of UA or UA-Lipo revealed no marked effect (FICI = 1.30-2.50). The UA-Lipo may be used as a dosage form to improve the antimycobacterial activity of RIF, a first-line drug for the treatment of infections caused by Mtb.

Glutamine-Loaded Liposomes: Preliminary Investigation, Characterization, and Evaluation of Neutrophil Viability.

Glutamine has received attention due to its ability to ameliorate the immune system response. Once conventional liposomes are readily recognized and captured by immune system cells, the encapsulation of glutamine into those nanosystems could be an alternative to reduce glutamine dosage and target then to neutrophils. Our goals were to nanoencapsulate glutamine into conventional liposomes (Gln-L), develop an analytical high-performance liquid chromatography (HPLC) method for its quantification, and evaluate the viability of neutrophils treated with Gln-L. Liposomes were prepared using the thin-film hydration technique followed by sonication and characterized according to pH, mean size, zeta potential, and drug encapsulation efficiency (EE%). We also aimed to study the effect of liposomal constituent concentrations on liposomal characteristics. The viability of neutrophils was assessed using flow cytometry after intraperitoneal administration of free glutamine (Gln), Gln-L, unloaded-liposome (UL), and saline solution as control (C) in healthy Wistar rats. The selected liposomal formulation had a mean vesicle size of 114.65 ± 1.82 nm with a polydispersity index of 0.30 ± 0.00, a positive surface charge of 36.30 ± 1.38 mV, and an EE% of 39.49 ± 0.74%. The developed chromatographic method was efficient for the quantification of encapsulated glutamine, with a retention time at 3.8 min. A greater viability was observed in the group treated with glutamine encapsulated compared to the control group (17%), although neutrophils remain viable in all groups. Thus, glutamine encapsulated into liposomes was able to increase the number of viable neutrophils at low doses, thereby representing a promising strategy for the treatment of immunodeficiency conditions.