Advanced theranostic nanoplatforms for hypericin delivery in the cancer treatment.

Biomodified coated-lipid vesicles were obtained using the DPPC lipid (L) and F127 copolymer linked covalently with spermine (SN), biotin (BT), and folic acid (FA), resulting in LF127-SN, LF127-BT, and LF127-FA nanoplatforms. The photosensitizer hypericin (HY) was incorporated into the nanosystem by a thin-film method and characterized by dynamic light scattering, zeta potential, encapsulation efficiency, and transmission electronic microscopy. The results provided a good level of stability for all nanoplatforms for at least 5 days as an aqueous dispersion. The in vitro serum stability showed that the HY-loaded LF127-SN has a lower tendency to form complexes with BSA protein than with its analogs. LF127-SN was the most stable HY formulation, followed by LF127-BT and LF127-FA, confirmed by the association constant (Kd) values: 600 µmol L-1, 1100 µmol L-1, 515 µmol L-1, and 378 µmol L-1 for LF127, LF127 FA, LF127-BT, and LF127-SN, respectively. The photodynamic potential of HY was accessed by cytotoxicity assays using Caco-2, B16-F10, L-929, and HaCat cells. HY-loaded LF127-SN revealed a significant increase in the selectivity compared to other nanoplatforms. HY-loaded in LF127-BT and LF127-SN showed distinct uptake and biodistribution after 2 h of intravenous application. All biomodified coated-lipids showed satisfactory metabolism within 72 h after application, without significant accumulation or residue in any vital organ. These results suggest that incorporating HY-loaded in these nanosystems may be a promising strategy for future applications, even with a small amount of binders to the coating copolymer (0.02% w/v). Furthermore, these results indicate that the LF127-SN showed remarkable superiority compared to other evaluated systems, being the most distinct for future photodynamic therapy and theranostic applications.

Boosting the photodynamic activity of erythrosine B by using thermoresponsive and adhesive systems containing cellulose derivatives for topical delivery.

Erythrosine displays potential photodynamic activity against microorganisms and unhealthy cells. However, erythrosine has high hydrophilicity, negatively impacting on permeation through biological membranes. Combining biological macromolecules and thermoresponsive polymers may overcome these erythrosine-related issues, enhancing retention of topically applied drugs. The aim of this work was to investigate the performance of adhesive and thermoresponsive micellar polymeric systems, containing erythrosine in neutral (ERI) or disodium salt (ERIs) states. Optimized combinations of poloxamer 407 (polox407) and sodium carboxymethylcellulose (NaCMC) or hydroxypropyl methylcellulose (HPMC) were used as platforms for ERI/ERIs delivery. The rheological and mechanical properties of the systems was explored. Most of the formulations were plastic, thixotropic and viscoelastic at 37 °C, with suitable gelation temperature for in situ gelation. Mechanical parameters were reduced in the presence of the photosensitizer, improving the softness index. Bioadhesion was efficient for all hydrogels, with improved parameters for mucosa in contrast to skin. Formulations composed of 17.5 % polox407 and 3 % HPMC or 1 % NaCMC with 1 % (w/w) ERI/ERIs could release the photosensitizer, reaching different layers of the skin/mucosa, ensuring enough production of cytotoxic species for photodynamic therapy. Functional micelles could boost the photodynamic activity of ERI and ERIs, improving their delivery and contact time with the cells.

Plastic ingestion by carnivore fish in a neotropical floodplain: seasonal and interspecific variations.

Some studies have shown that freshwater ecosystems are polluted in a similar proportion to marine ecosystems; however, there are many gaps to be filled in this topic. Here, we investigated whether plastics were consumed by carnivore fishes in a Neotropical floodplain and whether it was connected to seasonality (dry and wet seasons). We also evaluated the association between each type of plastic and the fish species. We analyzed the gastrointestinal contents of 23 species and assessed the occurrence and number of plastic particles. Plastics were obtained through chemical digestion and the spectrum of each sample, using a FT-IR imaging microscope. We performed a correspondence analysis (CA) with plastic data to assess the relationship between each type of plastic and the fish species. We also performed linear regression models to assess the relationships of occurrence and number of plastics ingested with seasonality. Nine species had plastics in their gastrointestinal contents, and they were identified as polyvinyl alcohol (PVA), polyamide (PA), polyethylene (PE), polystyrene (PS), and polypropylene (PP). The number of plastics had a positive relationship with the wet season, while the occurrence did not show a significant relationship with any season. These results are particularly important when considering the socioeconomic relevance and the ecological importance of this trophic guild.

Photo-Phytotherapeutic Gel Composed of Copaifera reticulata, Chlorophylls, and k-Carrageenan: A New Perspective for Topical Healing.

Chronic wound healing represents an impactful financial burden on healthcare systems. In this context, the use of natural products as an alternative therapy reduces costs and maintains effectiveness. Phytotherapeutic gels applied in photodynamic therapy (PDT) have been developed to act as topical healing medicines and antibiotics. The bioactive system is composed of Spirulina sp. (source of chlorophylls) and Copaifera reticulata oil microdroplets, both incorporated into a polymeric blend constituted by kappa-carrageenan (k-car) and F127 copolymer, constituting a system in which all components are bioactive agents. The flow behavior and viscoelasticity of the formulations were investigated. The photodynamic activity was accessed from studies of the inactivation of Staphylococcus aureus bacteria, the main pathogen of hospital relevance. Furthermore, in vivo studies were conducted using eighteen rabbits with dermatitis (grade III and IV) in both paws. The gels showed significant antibiotic potential in vitro, eliminating up to 100% of S. aureus colonies in the presence or absence of light. The k-car reduced 41% of the viable cells; however, its benefits were enhanced by adding chlorophyll and copaiba oil. The animals treated with the phytotherapeutic medicine showed a reduction in lesion size, with healing and re-epithelialization verified in the histological analyses. The animals submitted to PDT displayed noticeable improvement, indicating this therapy's viability for ulcerative and infected wounds. This behavior was not observed in the iodine control treatment, which worsened the animals' condition. Therefore, gel formulations were a viable alternative for future pharmaceutical applications, aiming at topical healing.

Multifunctional Nanoparticles as High-Efficient Targeted Hypericin System for Theranostic Melanoma.

Biotin, spermine, and folic acid were covalently linked to the F127 copolymer to obtain a new drug delivery system designed for HY-loaded PDT treatment against B16F10 cells. Chemical structures and binders quantification were performed by spectroscopy and spectrophotometric techniques (1NMR, HABA/Avidin reagent, fluorescamine assay). Critical micelle concentration, critical micelle temperature, size, polydispersity, and zeta potential indicate the hydrophobicity of the binders can influence the physicochemical parameters. Spermine-modified micelles showed fewer changes in their physical and chemical parameters than the F127 micelles without modification. Furthermore, zeta potential measurements suggest an increase in the physical stability of these carrier systems. The phototherapeutic potential was demonstrated using hypericin-loaded formulation against B16F10 cells, which shows that the combination of the binders on F127 copolymer micelles enhances the photosensitizer uptake and potentializes the photodynamic activity.

Photodamage on Staphylococcus aureus by natural extract from Tetragonia tetragonoides (Pall.) Kuntze: Clean method of extraction, characterization and photophysical studies.

Photodynamic therapy (PDT) is a clinical modality that allows the destruction of tumor cells and microorganisms by reactive oxygen species, formed by the combination of photosensitizer (PS), molecular oxygen and adequate wavelength light. This research, through a clean methodology that involves pressurized liquids extraction (PLE), obtained a highly antimicrobial extract of Tetragonia tetragonoides, which rich in chlorophylls as photosensitizers. The Chlorophylls-based extract (Cbe-PLE) presented pharmacological safety, through the maintenance of cellular viability. In addition, Cbe-PLE showed great efficacy against Staphylococcus aureus, with severe dose-dependent damage to the cell wall of the pathogen. The obtained product has a high potential for the development of photostimulated phytotherapic formulations for clinical applications in localized infections, as a complementary therapeutic alternative to antibiotics.

Hypericin photodynamic activity. Part III: in vitro evaluation in different nanocarriers against trypomastigotes of Trypanosoma cruzi.

Chagas is a parasitic endemic disease caused by the protozoan Trypanosoma cruzi. It represents a strong threat to public health due to its strong resistance against commonly available drugs. We studied the in vitro ability to inactivate the trypomastigote form of this parasite using photodynamic inactivation of microorganisms (or antimicrobial Photodynamic Therapy, aPDT). For this, we chose to use the photosensitizer hypericin (Hyp) formulated in ethanol/water (1% v/v) and Hyp loaded in the dispersion of different aqueous nanocarrier systems. These included polymeric micelles of F-127 and P-123 (both Pluronic™ surfactants), and liposomal vesicles of phospholipid 2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). These systems with Hyp had their activity compared against trypomastigote forms under light and in the dark. Hyp revealed a high level of effectiveness to eradicate protozoa in vitro. Samples at concentrations higher than 0.8 µmol L-1 of Hyp in Pluronic micelles showed efficacy even in the dark, with the EC50 around (6-8) µmol L-1. Therefore, Hyp/Pluronics can be used also as a chemotherapeutic agent. The best result for EC50 is at approximately 0.31 µmol L-1 for illuminated systems of Hyp in F-127 micelles. For Hyp in P-123 micelles under light, the results also led to a low EC50 value of 0.36 µmol L-1. The highest value of EC50 was 2.22 µmol L-1, which was found for Hyp/DPPC liposomes under light. For the Hyp-free (ethanol/water, 1% v/v)/illuminated group, the EC50 value was 0.37 µmol L-1, which also is a value that shows effectiveness. However, in free-form, Hyp is not protected against blood components, unlike when Hyp is loaded into the nanocarriers.