San Sebastián University

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 f 2 mol of VDG per mole of dendrimer, approximately twice that of the native G4 system. The resulting nanoparticles displayed a hydrodynamic diameter of 419.9 f 199.6 nm (PdI = 0.53 f 0.14) and a positive zeta potential of 18.6 f 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. Furthermore, in vitro cytotoxicity studies in A375 cells demonstrated that the G4-PEG:VDG formulation significantly reduced cell viability after 24 h of incubation, whereas the native dendrimer systems showed a markedly lower biological effect. Finally, skin interaction was evaluated during 1 h through the Saarbr & uuml;cken 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, supporting its potential use as a localized topical delivery system for VDG. Overall, PEGylation improved VDG encapsulation efficiency and promoted a more sustained drug release profile relative to native dendrimers. The combination of enhanced drug loading, sustained release, and preserved biological activity highlights the potential of partially PEGylated PAMAM dendrimers as nanocarriers for localized Vismodegib delivery. 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.

Background The femoral circumflex arteries (FCAs), arising from the femoral and profunda femoris arterial system, exhibit substantial anatomical variability and are clinically relevant due to their role in supplying the femoral head and proximal thigh musculature. These variations may affect surgical, vascular, reconstructive, and anesthetic procedures in the femoral region. The objective of this study is to systematically evaluate the prevalence of FCA anatomical variants, characterize their patterns, and assess their clinical and surgical implications. Methods A systematic search was performed across PubMed/MEDLINE, Scopus, Web of Science, Google Scholar, CINAHL, and LILACS up to July 2025. Studies describing morphological or branching variants of the medial or lateral FCA were included. Methodological quality was assessed using the Anatomical Quality Assurance tool. A random-effects model estimated pooled prevalences and subgroup differences. Thirty-six studies met the eligibility criteria, of which 29 contributed data to the quantitative meta-analysis. Results The global pooled prevalence of FCA variations was 56% (95% confidence interval [CI]: 46%–66%) with high heterogeneity (I2 = 99.5%). No significant laterality predominance was observed. Regional subgroup analysis demonstrated higher prevalence in European populations (33%, 95% CI: 25%–42%) relative to Asian populations (28%, 95% CI: 20%–36%). Sex-specific analysis showed a greater prevalence in females (72%, 95% CI: 59%–84%) than in males (42%, 95% CI: 29%–54%). Variations primarily involved origin, branching pattern, and course of the FCAs. Conclusion Anatomical variations of the FCAs are common and exhibit significant geographic and sexual variability. Based on this, we have proposed a classification of the probability of iatrogenic injury according to FCA variant and its relationship to the main surgical approaches to the hip.

The pursuit of atomically precise molecular clusters favors the finding of potential nano-sized species, improving their fundamental understanding. Here, we predict a Sc@Ag16+ cluster featuring a sixteen-vertex endohedral architecture, which resembles the characterized Rh4B12 ligand-decorated metallaborane, pushing the classical icosahedral limit. The electronic structure is given by a 18-cluster electron 1S21P61D10 superatomic configuration with an inherent formation of a long-range shielding cone for any orientation of the external field, confirming its spherical aromatic character. These results reveal Sc@Ag16+ as a truly spherical aromatic superatom, providing grounds for designing principles aiming non-icosahedral atom-precise metallic nanoclusters, as a template for medium-sized species.

This review critically examines the integration of nanocarriers into oral tablet formulations, focusing on compaction strategies, excipient selection, and the impact of nanosystem properties on manufacturability, drug release, and biopharmaceutical performance. A comprehensive literature search was conducted in PubMed and Web of Science to identify peer-reviewed publications reporting oral tablet formulations based on nanocarriers, including polymeric nanoparticles, liposomes, mesoporous silica nanoparticles (MSNs), dendrimers, and hybrid or lipid-based nanosystems. Relevant data on formulation strategies, compression methods, excipients, in vitro and in vivo performance, and critical quality attributes were extracted and analyzed. After removing duplicates and assessing relevance, 40 studies were selected for in-depth review. Polymeric nanoparticles consistently enhanced controlled release, with chitosan, polylactide acid, and casein-based systems enabling mucoadhesion or delayed dissolution. Silica-based nanocarriers, particularly MSNs, enhanced powder flow and tablet hardness when used within an optimal concentration range, whereas higher loadings negatively affected compressibility. Lipid nanoparticles and self-emulsifying systems facilitated immediate or sustained release while improving drug solubility. Freeze-drying, spray drying, and 3D printing were pivotal for stabilizing sensitive carriers. Hybrid systems, including metal–organic frameworks and chitosomes, provided tailored release and pharmacokinetic enhancement. Challenges included aggregation, poor flow, mechanical fragility, and regulatory limitations, though advances in excipient engineering, smart coatings, and manufacturing technologies are mitigating these barriers. Nanocarrier-based tablets are a promising frontier for improving oral drug delivery, offering controlled release, enhanced bioavailability, and potential for multifunctionality. While nanocrystal-based products dominate the market, newer nanosystems show increasing promise. Future directions include personalized therapies, oral delivery of biologics, and integration of multifunctional nanocarriers enabled by emerging technologies such as 3D printing and stimuli-responsive coatings.

El sedentarismo se relaciona con disminución a la sensibilidad de insulina y acumulación de tejido adiposo visceral. Lo que sumado a malos hábitos alimentarios, explican en parte el aumento global de sobrepeso y obesidad. En Chile el exceso de peso afecta a 64,4% y el sedentarismo al 88,6% de la población.El objetivo es determinar los niveles de sedentarismo en los estudiantes de la carrera de Nutrición y Dietética y evaluar si existe asociación con sus hábitos alimentarios. Se evaluaron 607 estudiantes de la carrera de Nutrición y Dietética aplicándoles una evaluación antropométrica de peso y talla, una encuesta de evaluación alimentaria y una encuesta de actividad física. Resultados: El porcentaje de mujeres sedentarias fue significativamente mayor que en los hombres (74,3% v/s 40,5%). Además,las mujeres que nunca cenabancasi duplicaron el porcentaje observado en los hombres. Finalmente,al comparar 2 grupos de estudiantes, unocompuesto por los que nunca desayunaban, ni cenaban y otro por los que desayunaban y cenaban todos los días,se determinó que existe asociación entre actividad física y la conducta alimentaria (♩2= 10,56; p=0.001) En este estudio se determinó que los individuos jóvenes sedentarios presentaban un mal comportamiento alimentario que quienes realizaban algún tipo de actividad física. Nuestros resultados sugieren que realizar algún tipo de actividad física se asocia a un mejor patrón de alimentación.