The aim of this work was to develop dendrimer-based nanocarriers of Vismodegib (VDG) for the topical treatment of Kaposi's sarcoma (KS). Previous molecular docking studies have shown that VDG is capable of inhibiting cyclooxygenase-2 (COX-2), an enzyme transcriptionally induced by the viral oncoprotein vGPCR and critically involved in the angioproliferative phenotype of KS. In this study, VDG was complexed with generation 4 poly(amidoamine) (PAMAM) dendrimers bearing hydroxyl terminal groups (G4-OH), and surface-functionalized with folic acid (G4-FA). The resulting G4-OH@VDG and G4-FA@VDG complexes significantly enhanced the apparent aqueous solubility of VDG, achieving experimental stoichiometries of approximately 4 and 8 mol of VDG per mole of dendrimer, respectively. G4-OH@VDG displayed a hydrodynamic diameter of 225.1 ± 122.0 nm (PdI = 0.44 ± 0.02), while G4-FA@VDG exhibited a size of 210.5 ± 54.7 nm (PdI = 0.66 ± 0.08). Dendrimer-drug associations were confirmed by FT-IR spectroscopy, and in vitro release studies revealed distinct, pH-dependent release mechanisms. Cytotoxicity was evaluated using ex vivo (red blood cells) and in vitro (HaCaT keratinocytes) models, both relevant to topical KS treatment, and no cytotoxic effects were observed. Skin penetration studies using the Saarbrücken ex vivo model demonstrated that both systems were able to deliver VDG into the skin, with G4-OH@VDG achieving higher drug accumulation, particularly within the stratum corneum. Antitumoral activity was assessed in an in vitro KS model, where cytotoxic effects were observed at 48 h post-incubation. Notably, G4-OH@VDG exhibited the most favorable therapeutic profile, including significant reduction of cell viability and inhibition of cell migration at sublethal concentrations. Overall, these results demonstrate that the combination of drug repurposing and dendrimer-based nanotechnology for topical delivery enhances the therapeutic performance of VDG in in vitro models of Kaposi's sarcoma.

The aim of this study was to evaluate how the degree of PEGylation of fourth-generation PAMAM dendrimers (G4) influences Vismodegib (VDG) encapsulation, release behavior, hemocompatibility, and skin interaction. In recent years, VDG has been incorporated into diverse drug delivery systems to modify its route of administration, enhance targeted action, and reduce systemic side effects. In this context, PAMAM G4 dendrimers have emerged as promising nanocarriers to improve the aqueous solubility of hydrophobic drugs. However, their cationic surface charge may lead to concentration-dependent cytotoxicity. Surface PEGylation has been proposed as an effective strategy to improve biocompatibility while potentially increasing drug loading capacity. Herein, G4-PEG dendrimers with different degrees of surface modification were synthesized and characterized by 1H-NMR spectroscopy. Among the synthesized systems, the 20% PEGylated dendrimer showed the highest drug-loading capacity, forming G4-PEG:VDG complexes with an experimental stoichiometry of 10±2 moles of VDG per mole of dendrimer, approximately twice that of the native G4 system. The resulting nanoparticles displayed a hydrodynamic diameter of 419.9±199.6 nm (PdI= 0.53±0.14) and a positive zeta potential of 18.6±0.6 mV. FT-IR spectroscopy confirmed the supramolecular interaction between the dendrimer and VDG. In vitro release studies at pH 7.4 and 5.0 indicated that PEGylation enhanced the retention of VDG within the nanocarrier, producing a slower and more controlled release behavior. Ex vivo nanotoxicological assays using human erythrocytes showed low hemolytic activity, although time-dependent erythrocyte agglutination and morphological alterations were observed, highlighting safety aspects not captured by hemolysis assays alone. Finally, skin interaction was evaluated during 1 hour through the Saarbrücken penetration model, revealing that G4-PEG:VDG complexes remained predominantly confined to the stratum corneum, as confirmed by fluorescence monitoring of histological skin sections. This retention is attributed to the increased nanoparticle size and to interactions between PEG chains and cutaneous lipids, suggesting potential applicability for localized topical of carcinoma basocellular.Overall, PEGylation improved VDG encapsulation efficiency and promoted a more sustained drug release profile relative to native dendrimers. These results demonstrate that surface functionalization plays a key role in governing drug release kinetics, skin interaction, erythrocyte responses, emphasizing the need to finely tune PEGylation in the rational design of dendrimer-based drug delivery systems.

Antimicrobial resistance (AMR) represents a critical global health challenge, driving the need for innovative therapeutic strategies. This study introduces self-assembled nanoparticles based on fourth-generation polyamidoamine (PAMAM-G4) dendrimers and Phloxine B (PhB), forming G4-PhB nanoparticles as an advanced platform for antimicrobial photodynamic therapy (aPDT). The optimal dendrimer:dye molar ratio was determined through dynamic light scattering (DLS) titration experiments, yielding a 1:15 G4:PhB ratio. The resulting G4-PhB nanoparticles were spherical, with a hydrodynamic diameter of 260 ± 15 nm, a narrow polydispersity index (PDI) of 0.264 ± 0.085, and a positive zeta potential of 8.71 ± 2.88 mV, indicating monodispersity and colloidal stability. These features were corroborated by morphological analyses using TEM and AFM. Cytotoxicity assays conducted on murine fibroblasts (3 T3 cell line), using MTT, neutral red uptake, and crystal violet staining revealed that G4-PhB nanoparticles are intrinsically non-toxic, contrasting with the EDTA-PhB complex, which exhibited significant cytotoxic effects. Antibacterial activity was evaluated against Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA). While free PhB demonstrated bactericidal effects exclusively against SA, the G4-PhB nanoparticles exhibited enhanced activity against both bacterial strains, notably overcoming the limitations of free PhB against PA. These findings highlight the versatility and effectiveness of G4-PhB nanoparticles as a biocompatible and non-invasive system for localized aPDT, with potential applications in wound healing for immunocompromised patients. This work provides a robust foundation for future research into dendrimer-based photosensitizers as innovative solutions to pressing biomedical challenges.

Leishmania parasites are the organisms responsible for one of the most important tropical diseases, leishmaniasis. This neglected disease mainly affects populations in developing or underdeveloped countries, causing nearly one million new cases per year. This article focuses on the cutaneous form of the disease. Common antileishmanial medications have several disadvantages, such as low efficiency, high toxicity, several adverse effects, resistant strains, long treatments, and high costs. As a result, first- and second-line treatments are insufficient. Therefore, there is a need for new antileishmanial agents and strategies, most of which utilize nanotechnology. While novel nano-drug delivery devices can transport antileishmanial drugs to target cells, reducing secondary toxic effects, several advances in nanotechnology and photonics pursue activation of leishmanicidal mechanisms once they reach their target. Here is a summary of recent nanotechnology approaches to the treatment, diagnosis, and prevention of human cutaneous leishmaniasis, including promising techniques still in development.

The active blueberry compounds called anthocyanins have poor oxidation stability, but, if encapsulated by protein nanoparticles, they can be protected due to the slowing down of the oxidation process. This work describes the advantages of using a γ-irradiated bovine serum albumin nanoparticle bound to anthocyanins. The interaction was characterized biophysically, mainly by rheology. By computational calculation and simulation based on model nanoparticles, we estimated the number of molecules forming to the albumin nanoparticles, which allowed us to infer a ratio of anthocyanin/nanoparticles. Measurements by UV-VIS spectroscopy, FT-IR spectroscopy, fluorescence spectroscopy, dynamic light scattering (DLS), ζ potential, electron transmission microscopy and rheology at room (25 °C), and physiological (37 °C) temperatures were performed. The spectroscopy measurements allowed identifying additional hydrophobic sites created during the irradiation process of the nanoparticle. Based on the rheological studies, it was observed that for all the temperatures selected, the BSA-NP trend is a Newtonian flow behavior type, and there is a direct correlation between dynamic viscosity and temperature values. Furthermore, when anthocyanins are added, the system increases its resistance to the flow reflected in the morphological changes observed by TEM, confirming the relationship between viscosity values and aggregate formation

We analyzed amber samples from the the Baltic region and Mexico, as well as imitation amber, in order to develop an analytical method allowing to discriminate between different samples causing little or no damage. We propose a two-step method that involves the use of Laser Induced Breakdown Spectroscopy (LIBS) to obtain spectra, and Discriminant Analysis to analyze the resulting data. We studied the damage caused to the samples using confocal optical microscopy.

Raman spectroscopy was used to detect low quantities of Vismodegib in the skin after its topical application via transfersomes. Vismodegib is a novel antineoplastic drug approved for oral administration for treatment of basal cell carcinoma. Transfersomes loaded with Vismodegib were prepared by thin film resuspension and extrusion, and were characterized physicochemically. Transfersomes were applied to human and pig skin specimens using the Saarbrücken penetration model. The skin was then sectioned by tape stripping, followed by penetration assessment by UV-Vis spectroscopy and Raman spectroscopy in a confocal Raman microscope. Raman signals from Vismodegib and transfersomes were recovered from skin sections, showing a similar distribution in the stratum corneum obtained by the other techniques. On the other hand, pig and human skin showed differences in their penetration profiles, proving their lack of equivalence for assessing the performance of these transfersomes. Raman spectroscopy appears as a potential non-invasive, direct tool for monitoring hard-to-detect molecules in a complex environment such as the skin.

Vismodegib (VDG) is an antineoplastic, a first-in-class Hedgehog signaling pathway inhibitor, indicated to treat locally advanced or metastatic basal cell carcinoma. Treatment with this drug was approved in 2012 by the US-FDA for oral administration (dose of 150 mg per day) in patients with a refusal of radiotherapy or surgery. However, it presents side effects that influence patient adherence to treatment. Polyamidoamine (PAMAM) dendrimers (D) are promising drug-delivery systems with high water solubility. Additionally, they can penetrate the skin barrier. In this work, we used amine-terminated (DG4.0) and carboxy-terminated (DG4.5) dendrimers of generation 4.0 and 4.5, respectively. We demonstrated that the complexation of VDG with dendrimers (D:VDG complexes) increased its concentration in the aqueous medium. We carried out characterization studies of the complexes to understand how dendrimers interact with VDG, and we found the optimal molar ratios of complexation.Furthermore, as these dendrimers have shown non-traditional fluorescence, we studied the effect on the emission patterns of the D:VDG complexes. This feature allowed for fluorescence monitoring of skin penetration of the complexes, while RP-HPLC quantified VDG. Although the complexes managed to penetrate human skin explants, DG4.0:VDG presented a better penetration profile. The concentration of VDG complexed with dendrimers in the viable epidermis and dermis was 1.95 µg/ml and 5.47 µg/ml for DG4.0 and DG4.5, respectively. These results show the theragnostic potential of these formulations in treating basal cell carcinoma.

Perovskite solar cells (PSCs) have substantially increased their power conversion efficiency (PCE) to more than 25% in recent years. However, the instability of these devices is still a strong obstacle for their commercial applications. Recently, all-inorganic PSCs based on CsPbI3 and CsPbI2Br as the perovskite layer have shown enhanced long-term stability, which makes them potential candidates for commercialization. Currently, all-inorganic PSCs with inverted p-i-n configuration have not yet reached the high efficiency achieved in the normal n-i-p structure. However, the inverted p-i-n architecture has recently drawn attention of researchers because it is more suitable to prepare tandem solar cells. In this work, a theoretical study of inverted p-i-n all-inorganic PSCs based on CsPbI3 and CsPbI2Br as the perovskite layer was carried out using SCAPS-1D software (ver. 3.3.09). The performance of different architectures of PSC was examined and compared by means of numerical simulations using various inorganic materials as the hole transport layer (HTL) and the electron transport layer (ETL). The results reveal that CuI and ZnO are the most suitable as HTL and ETL, respectively. In addition, the performance of the devices was significantly improved by optimizing the hole mobility in CuI as well as the thickness, doping density, and defect density in the absorber layer. Maximum efficiencies of 26.5% and 20.6% were obtained under optimized conditions for the inverted all-inorganic CsPbI3- and CsPbI2Br-based PSCs, respectively. These results indicate that further improvements in the performance of such devices are still possible.

Vismodegib is a first-in-class inhibitor for advanced basal cell carcinoma treatment. Its daily oral doses present a high distribution volume and several side effects. We evaluated its skin penetration loaded in diverse nanosystems as potential strategies to reduce side effects and drug quantities. Ultradeformable liposomes, ethosomes, colloidal liquid crystals, and dendrimers were able to transport Vismodegib to deep skin layers, while polymeric micelles failed at this. As lipidic systems were the most effective, we assessed the in vitro and in vivo toxicity of Vismodegib-loaded ultradeformable liposomes, apoptosis, and cellular uptake. Vismodegib emerges as a versatile drug that can be loaded in several delivery systems for topical application. These findings may be also useful for the consideration of topical delivery of other drugs with a low water solubility.

The objective of this technical note is to present the results of employing a new, to the best of our knowledge, temporary synchronization device to the study of laser-induced plasma spectroscopy in a multi-pulse regime. By providing a means of controlling the time delay and the reading window of the spectrometer, this device allows the user to distinguish among the emissions from independent micro-pulses and groups of micro-pulses. Using this method, it is possible to optimize the reading of the spectra by choosing the most appropriate time delay and duration values of the spectral reading window.

In the last years, it has been discovered and intensely studied the non-traditional intrinsic fluorescence of PAMAM dendrimers. Nevertheless, their aging process in aqueous suspension is scarcely studied, being unknown the causes of the observed changes in their fluorescence properties. Hence, this work aims to characterize the PAMAM dendrimers of generation 4.0 (DG4.0) and 4.5 (DG4.5) through the aging process at three different pH conditions, stored with or without shaking. We studied, up to 16 days, the UV-Vis absorption, the fluorescence emission, and the size of dendrimers/aggregates. In a different way than the already published work, we demonstrated that there is no chemical change in dendrimers through the aging process, even though changes in fluorescence emission were observed. Besides, we have put in evidence that changes in the agglomeration patterns of dendrimers would not be related to change in the fluorescence emission thought aging. Moreover, we demonstrated that DG4.5 formed large aggregates in water that need to be disrupted by shaking previous to an in vivo administration.

El objetivo del trabajo denominado “Nanoformulaciones basadas en nanoparticulas de metal liquido con superficie modificada”, es el desarrollo y caracterizacion biofisica de nanoformulaciones como transportadores de drogas antitumorales especificas para el tratamiento de cancer de colon. Los farmacos que se emplearan son: el 5 fluoracilo (5-FU) y el Regorafenib (REG). Lo novedoso de dicho trabajo de investigacion es la implementacion de lipidos fotopolimerizables y el de nanoparticulas de metal liquido, cuya biocompatibilidad ha sido demostrada recientemente por Chechetka et al, 2017. Estos nanotransportadores son fotosensibles, cuando se iluminan con radiacion laser de baja intensidad aumentan su temperatura gracias a la absorcion plasmonica que presentan. Al mismo tiempo que elevan la temperatura generan especies reactivas de oxigeno (ROS). Teniendo presente las caracteristicas que presentan las nanoparticulas a utilizar, se espera controlar la proliferacion tumoral por 3 vias: mediante la droga encapsulada en las nanoparticulas de metal liquido, el incremento de temperatura y la actividad oxidante de las ROS. Un paso importante es realizar experimentos de citotoxicidad y de viabilidad celular en distintas lineas celulares, para ello se utilizara CaCo2 como modelo de adenocarcinoma de colon y HeLa como modelo general.

We analyzed the ablation dynamics for Silicon atoms located in two different environments. Experiments were done with semiconductor (silicon wafer) and a dielectric material (fused silica). We point out some difference in plasma dynamics for Silicon in both environments. Those results can not be explained with current and accepted theoretical models, which asseverate that after the femtosecond laser pulse interact with the surface, the process evolve as metal regardless the kind of material under excitation. Electronic density and temperature were measured with temporal resolution on SiO2 and Si samples by using standard fs LIBS imaging spectroscopy. Extinction time of both plasmas is different depending on the kind of sample under irradiation. Lifetime for plasma obtained in dielectric sample is shorter than that of semiconductor. The main reason to explain this behavior is related to the deep defect induced in the dielectric (fused silica) gap by the femtosecond process; these centers act as sink for the free electron promoted by the laser interaction from the valence band to the plasma, so for dielectrics, shorter lifetime plasmas are obtained when femtosecond pulse irradiation is conducted.

This work presents a design of a low-cost spray pyrolysis automatized system which allows to manufacture high quality thin films. In particular, the thermal component of this instrument is modelled in different operation conditions, analyzed, and controlled. Also, different configurations for the whole instrument are analyzed.

El objetivo general de este plan de trabajo es contribuir al tratamiento de la leishmaniasis cutanea (LC) por medio del desarrollo de una terapia basada en la activacion por pulsos laser de nanosistemas fotosensibles que accederian a las poblaciones celulares infectadas a traves de la via topica, evitando la distribucion sistemica con la disminucion consecuente de efectos colaterales y aumentando la especificidad de su accion antiparasitaria. De este se desprende como objetivo especifico el desarrollo de formulaciones topicas basadas en etosomas ultraflexibles que favorezcan el transporte a traves del estrato corneo de nanoparticulas efectoras de terapia fotodinamica basadas en carbono (carbon quantum dots). Estos sistemas deberan caracterizarse biofisica y bioquimicamente, asi como debera estudiarse su fototoxicidad sobre formas libres e intracelulares de Leishmania sp. Conjuntamente, el desarrollo de un metodo de deteccion por tecnicas fotonicas permitira estudiar su penetracion en piel obteniendo informacion diagnostica a la vez que induce su accion terapeutica. La importancia de este trabajo radica en que la leishmaniasis cutanea es una enfermedad endemica en el Norte de la Argentina (Grimaldi Jr et al., 1989). Causada por algunas especies del protozoo intracelular Leishmania (Lainson y Shaw, 1987), infecta al ser humano y a otros mamiferos. La LC requiere de tratamientos prolongados y dolorosos para lograr su cura, e incluso luego del tratamiento la enfermedad puede evolucionar hacia formas desfigurantes e inhabilitantes, disparando procesos inflamatorios que conllevan riesgo de vida. Convencionalmente, la LC se trata con soluciones de antimoniales pentavalentes, de alta toxicidad y que, ademas de generar resistencia, son poco efectivas para llegar hasta los nidos de amastigotes en los fagosomas de los macrofagos de la epidermis profunda. Cabe destacar que la terapia con antimoniales pentavalentes data de 1912 (Vianna, 1912). Desde ese momento hasta la actualidad, ese continua siendo el tratamiento de primera linea, pese a los numerosos efectos colaterales que conlleva. Frente a la busqueda de nuevos tratamientos, la nanotecnologia provee herramientas que permiten el transporte direccionado de drogas, mediante el uso de nanosistemas de entrega de activos (NEA) para lograr el control espacio-temporal de la llegada del activo a las celulas blanco (Koo et al., 2005). Un NEA topico es el basado en etosomas, que estan compuestos de fosfolipidos, agua y etanol. Este ultimo cumple la funcion de facilitador de permeacion, ya que colabora en la separacion temporal de las capas del EC, aumentando la penetracion de los activos que incorpora. A su vez, la terapia fotodinamica es una forma de generar toxicidad sobre porciones de tejido muy localizada. La misma se basa en moleculas que, tras su fotoactivacion, generan especies reactivas del oxigeno que oxidan biomoleculas ricas en electrones produciendo muerte celular (Jimenez Banzo, 2008).

Physicochemical characterization of polyamidoamine (PAMAM) dendrimers of generation 4.0 amine-terminated (DG4.0) and 4.5 carboxy-ended (DG4.5) was done. We have measured the pKa of the inner tertiary amine, the surface primary-amine, and carboxyl-terminal groups. We have conducted UV-Vis absorption and fluorescence emission experiments as a function of pH. We have made a 4th derivative analysis of the UV-Vis absorption experiments and compare the results with classical amide such as dimethylformamide. Our results have permitted us to calculate the pKa of the groups sensible to the pH in both dendrimers and compare the results with theoretical studies. On the one hand, the pKa values found for DG4.0 were 10.0 +/- 0.5 and 7.1 +/- 0.2, for primary and tertiary amines groups, respectively. On the other hand, the pKa values found for the DG4.5 were 3.5 +/- 0.7 and 6.8 +/- 0.4, for the carboxylic and tertiary amine groups. Our experimental results agree with theoretical ones. We offer probes that the dendrimers have two non-traditional fluorophores, where one of them is the inner amide bond. The dendrimers show fluorescence emission in all the tested pH.