Recent Trends in Curcumin-Containing Inorganic-Based Nanoparticles Intended for In Vivo Cancer Therapy.

Curcumin is a natural compound that has been widely investigated thanks to its various biological properties, including antiproliferative. This molecule acts on different cancers such as lung, breast, pancreatic, colorectal, etc. However, the bioactive actions of curcumin have limitations when its physicochemical properties compromise its pharmacological potential. As a therapeutic strategy against cancer, curcumin has been associated with inorganic nanoparticles. These nanocarriers are capable of delivering curcumin and offering physicochemical properties that synergistically enhance anticancer properties. This review highlights the different types of curcumin-based inorganic nanoparticles and discusses their physicochemical properties and in vivo anticancer activity in different models of cancer.

Flours from Spondias mombin and Spondias tuberosa seeds: Physicochemical characterization, technological properties, and antioxidant, antibacterial, and antidiabetic activities.

Yellow mombin (Spondias mombin) and Brazil plum (Spondias tuberosa) seeds are byproducts of exploiting their pulp and currently have no relevant food or industrial applications. Thus, the present study aimed to evaluate the physicochemical, technological, and functional characteristics of flours obtained from yellow mombin (YMF) and Brazil plum (BPF) residues. The flours presented a high percentage of insoluble fiber (68.8-70.2 g/100 g) and low carbohydrate (2.7-4.0 g/100 g) and caloric (91.9-95.3 kcal) values. The flours showed potential for technological application. In addition, the highest concentration of total phenolic content (31.1-50.2 mg GAE/g) was obtained with 70% acetone, which provided excellent results for antioxidant capacity evaluated by 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (81.0%-89.7%) and 2,2-diphenyl-1-picrylhydrazyl (60.6%-69.1%) radical scavenging capacity assays. Flour extracts in 70% acetone also exhibited inhibition of α-amylase (63.3%-78.8%) and amyloglucosidase (63.5%-71.0%). The antibacterial study revealed that extracts inhibited the growth of Escherichia coli, Burkholderia cepacia, and Burkholderia multivorans. Therefore, this study suggests the use of yellow mombin and Brazil plum residues for different food or industrial applications. PRACTICAL APPLICATION: The knowledge gained from this study will open a new approach to add value to yellow mombin and Brazil plum fruit seeds as sources of fiber and bioactive compounds, with promising application in the formulation of functional and nutraceutical products, benefiting both a sustainable environment and a sustainable industry.

Lippia origanoides essential oil increases longevity and ameliorates ß-amyloid peptide-induced toxicity in Caenorhabditis elegans.

Lippia origanoides essential oil (LOEO) is extensively utilised as food preservative due to its antioxidant and antibacterial activities. In this study, the antioxidant and anti-ageing effects of LOEO was investigated in vivo using the nematode Caenorhabditis elegans. The gas chromatography-mass spectrometry analysis indicated that the main components of LOEO are carvacrol and thymol. LOEO treatment improved physiological parameters such as pharyngeal pumping, locomotion and body size indicating that is not toxic to C. elegans. LOEO treatment showed antioxidant effect in C. elegans by reducing endogenous ROS (Reactive Oxygen Species) production and increasing their survival under oxidative stress. Finally, LOEO treatment significantly extended C. elegans lifespan and alleviated the paralysis induced by ß-amyloid peptide overexpression in the muscle. This work demonstrates for the first time LOEO antioxidant and anti-ageing properties on an organism level providing a valuable proof of principle to support further studies in the development of nutraceuticals or antioxidant phytotherapy.

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.

Triazole-substituted phenylboronic acids as tunable lead inhibitors of KPC-2 antibiotic resistance.

Inhibition of ß-lactamases is a promising strategy to overcome antimicrobial resistance to commonly used ß-lactam antibiotics. Boronic acid derivatives have proven to be effective inhibitors of ß-lactamases due to their direct interaction with the catalytic site of these enzymes. We synthesized a series of phenylboronic acid derivatives and evaluated their structure-activity relationships as Klebsiella pneumoniae carbapenemase (KPC-2) inhibitors. We identified potent KPC-2 inhibitors 2e & 6c (Ki = 0.032 µM and 0.038 µM, respectively) that enhance the activity of cefotaxime in KPC-2 expressing Escherichia coli. The measured acid dissociation constants (pKa) of selected triazole-containing phenylboronic acids was broad (5.98-10.0), suggesting that this is an additional property of the compounds that could be tuned to optimize the target interaction and/or the physicochemical properties of the compounds. These findings will help to guide the future development of boronic acid compounds as inhibitors of KPC-2 and other target proteins.

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.

Development, Characterization, and Immunomodulatory Evaluation of Carvacrol-loaded Nanoemulsion.

Carvacrol (CV) is an essential oil with numerous therapeutic properties, including immunomodulatory activity. However, this effect has not been studied in nanoemulsion systems. The objective of this study was to develop an innovative carvacrol-loaded nanoemulsion (CVNE) for immunomodulatory action. The developed CVNE comprised of 5% w/w oily phase (medium chain triglycerides + CV), 2% w/w surfactants (Tween 80®/Span 80®), and 93% w/w water, and was produced by ultrasonication. Dynamic light scattering over 90 days was used to characterize CVNE. Cytotoxic activity and quantification of cytokines were evaluated in peripheral blood mononuclear cell (PBMC) culture supernatants. CVNE achieved a drug loading of 4.29 mg/mL, droplet size of 165.70 ± 0.46 nm, polydispersity index of 0.14 ± 0.03, zeta potential of -10.25 ± 0.52 mV, and good stability for 90 days. CVNE showed no cytotoxicity at concentrations up to 200 µM in PBMCs. CV diminished the production of IL-2 in the PBMC supernatant. However, CVNE reduced the levels of the pro-inflammatory cytokines IL-2, IL-17, and IFN-γ at 50 µM. In conclusion, a stable CVNE was produced, which improved the CV immunomodulatory activity in PBMCs.

Antimicrobial and anthelmintic activities of the ethanolic extract, fractions and isolated compounds from Manilkara zapota L. P. Royen (Sapotaceae).

OBJECTIVES: To evaluate the antibacterial, antifungal and anthelmintic activities of the ethanolic extract (EEMz), fractions (LPFMz and HPFMz) and compounds isolated from the leaves of Manilkara zapota L. P. Royen. METHODS: Extract and fractions were produced by turbolization. LPFMz fraction was analysed by gas chromatography-mass spectrometry. The isolated compounds from HPFMz were purified by flash and preparative chromatographic methods, and chemically characterised by UPLC-ESITOFMS, optical rotation, and one- and two-dimensional 1H and 13C NMR techniques. Anthelmintic against Strongyloides venezuelensis and antimicrobial activities against Candida albicans, Trichophyton rubrum and Staphylococcus aureus were evaluated. KEY FINDINGS: EEMz showed mainly phenolic compounds and pentacyclic triterpenes from Δ12-oleane/Δ12-ursane series. Chlorogenic acid, myricetin-3-O-ß-D-glucopyranoside, mearnsitrin, germanicol and germanicol acetate were reported to M. zapota leaves for the first time in this work. EEMz, HPFMz, LPFMz showed significative activity against C. albicans (16 µg/mL), while isolated flavonoids were active against S. aureus (<32 µg/mL). EEMz, phenolic-rich compounds (F2), and chlorogenic acid were potentially active against S. venezuelensis at 24 h. CONCLUSIONS: M. zapota and its bioactive compound can be eligible such as a potential phytomedicine for the treatment of microbial and strongyloidiasis drug-resistant infections.

Development of a Gas Chromatography Method for the Analysis of Copaiba Oil.

A rapid, simple, precise and economic method for the quantification of main compounds of copaiba resin and essential oils (Copaifera langsdorffii Desf.) by gas chromatography (GC) has been developed and validated. Copaiba essential oil was extracted by hydrodistillation from the copaiba resin. Resin derivatization allowed the identification of diterpenes compounds. A gas chromatography-mass spectroscopy (GC/MS) method was developed to identify compounds composing the copaiba resin and essential oil. Then the GC/MS method was transposed to be used with a flame ionization detector (FID) and validated as a quantitative method. A good correlation between GC/MS and GC/FID was obtained favoring method transposition. The method showed satisfactory sensitivity, specificity, linearity, precision, accuracy, limit of detection and limit of quantitation for ß-caryophyllene, α-humulene and caryophyllene oxide analyses in copaiba resin and essential oils. The main compounds identified in copaiba essential oil were ß-bisabolene (23.6%), ß-caryophyllene (21.7%) and α-bergamotene (20.5%). Copalic acid methyl ester (15.6%), ß-bisabolene (12.3%), ß-caryophyllene (7.9%), α-bergamotene (7.1%) and labd-8(20)-ene-15,18-dioic acid methyl ester (6.7%) were diterpenes identified from the derivatized copaiba resin. The proposed method is suitable for a reliable separation, identification and quantification of compounds present in copaiba resin and essential oil. It could be proposed as an analytical method for the analysis of copaiba oil fraction in raw and essential oil parent extracts and after they have been incorporate in pharmaceutical formulations.

Match of Solubility Parameters Between Oil and Surfactants as a Rational Approach for the Formulation of Microemulsion with a High Dispersed Volume of Copaiba Oil and Low Surfactant Content.

PURPOSE: Aim was to formulate oil-in-water (O/W) microemulsion with a high volume ratio of complex natural oil, i.e. copaiba oil and low surfactant content. The strategy of formulation was based on (i) the selection of surfactants based on predictive calculations of chemical compatibility between their hydrophobic moiety and oil components and (ii) matching the HLB of the surfactants with the required HLB of the oil. METHOD: Solubility parameters of the hydrophobic moiety of the surfactants and of the main components found in the oil were calculated and compared. In turn, required HLB of oils were calculated. Selection of surfactants was achieved matching their solubility parameters with those of oil components. Blends of surfactants were prepared with HLB matching the required HLB of the oils. Oil:water mixtures (15:85 and 25:75) were the titrated with surfactant blends until a microemulsion was formed. RESULTS: Two surfactant blends were identified from the predictive calculation approach. Microemulsions containing up to 19.6% and 13.7% of selected surfactant blends were obtained. CONCLUSION: O/W microemulsions with a high volume fraction of complex natural oil and a reasonable surfactant concentration were formulated. These microemulsions can be proposed as delivery systems for the oral administration of poorly soluble drugs.

Freeze-drying of emulsified systems: A review.

Colloidal systems such as emulsions, microemulsions and nanoemulsions are able to transport active molecules, enhance their solubility and stability and minimize their side effects. However, since they are dispersions with an aqueous continuous phase they have some disadvantages such as the risk of microbiological contamination, degradation by hydrolysis, physico-chemical instability and loss of pharmacological activity of the drug. Freeze drying, in which the water is removed from the preparation by sublimation under vacuum, has been suggested as a means to resolve these problems. Lyophilized products are very stable and are easy to transport and store. However, there is very little information in the literature about the application of this technique to emulsified systems. The aim of this review is to evaluate the lyophilization process as a tool for increasing the shelf life of emulsified systems such as emulsions, microemulsions and nanoemulsions. In addition, the mechanism of cryoprotection and the techniques that can be used to characterize the freeze-dried systems are discussed.