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Fluorescent organic nanoparticles (FONs) are a large family of nanostructures constituted by organic components that emit light in different spectral regions upon excitation, due to the presence of organic fluorophores. FONs are of great interest for numerous biological and medical applications, due to their high tunability in terms of composition, morphology, surface functionalization, and optical properties. Multifunctional FONs combine several functionalities in a single nanostructure (emission of light, carriers for drug-delivery, functionalization with targeting ligands, etc.), opening the possibility of using the same nanoparticle for diagnosis and therapy. The preparation, characterization, and application of these multifunctional FONs require a multidisciplinary approach. In this review, we present FONs following a tutorial approach, with the aim of providing a general overview of the different aspects of the design, preparation, and characterization of FONs. The review encompasses the most common FONs developed to date, the description of the most important features of fluorophores that determine the optical properties of FONs, an overview of the preparation methods and of the optical characterization techniques, and the description of the theoretical approaches that are currently adopted for modeling FONs. The last part of the review is devoted to a non-exhaustive selection of some recent biomedical applications of FONs., This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowka-Curie grant agreement No. 101007804 (Micro4Nano). M.K., N.V., and I.R. acknowledge financial support from the Spanish Ministry of Science and Innovation through the Severo Ochoa Program for Centers of Excellence in R&D (SEV-2015-0496 and CEX2019-000917-S) and through the grant “MOL4BIO” (PID2019-105622RB-I00). K.D.B acknowledges support from the US National Science Foundation (EFMA-2203704) and the National Institutes of Health (R21AA028340)., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).

The aim of the present study was to evaluate the influence of the incorporation of caffeine as a model active ingredient on the quality attributes of a bioadhesive emulgel formulation previously optimized by Quality by Design (QbD) tools. Emulgels are emerging topical drug delivery systems for cosmetic or pharmaceutical uses, which combine the advantages of both emulsions and gels.In this work, the observed and predicted values for spreadability, phase separation by centrifugation and detachment forces performed by texturometer were compared with those of the control and active-containing emulgel formulations. In addition, rheological properties, release of caffeine and comparative in vitro/ex vivo bioadhesion properties were evaluated using human skin.The flow curves of emulgel formulations showed the typical pseudoplastic and no thixotropic flow with yield stress. The incorporation of active ingredient did not produce significant changes. All emulgels were uniformly spread and no significant differences in spreadability values between control and caffeine containing formulations and neither respect to those predicted values from experimental design optimization were found. Emulgel formulations showed appropriate detachment forces values and no significant differences between caffeine loading and control emulgel formulations were observed.Caffeine was successfully vehiculized in this optimized bioadhesive emulgel formulation, which showed high robustness regarding the process variability. There were no significant changes in the critical quality attributes after the incorporation of the active ingredient and a promising stability was observed for at least one year. Results suggested that the optimized emulgel is an interesting topical biodhesive delivery system for cosmetic applications, including agents for skin conditioning, not present in gels formulations.OBJECTIF: la présente étude visait à évaluer l’influence de l’incorporation de la caféine comme une substance active modèle dans les attributs de qualité d’une préparation d’émulgel bioadhésif préalablement optimisée grâce à des outils QbD (Quality by Design, Qualité par la conception). Les émulgels sont des systèmes d’administration de médicaments topiques émergents destinés à des usages cosmétiques ou pharmaceutiques, qui associent les avantages des émulsions et des gels. MÉTHODES: dans cet étude, les valeurs observées et prédites en matière d’étalement, de séparation des phases par centrifugation et de forces de détachement par texturomètre ont été comparées à celles des préparations de contrôle et d’émulgel contenant des actifs. En outre, les propriétés rhéologiques, la libération de caféine et la comparaison des propriétés de bioadhérence in vitro / ex vivo ont été évaluées sur la peau humaine. RÉSULTATS: les courbes de débit des préparations d’émulgel révèlent un flux pseudoplastique typique et non thixotropique avec charge d’écoulement. L’incorporation de la substance active n’a pas produit de changements importants. Tous les émulgels ont été uniformément étalés et aucune différence significative dans les valeurs d’étalement entre les préparations de contrôle et celles contenant de la caféine n’a été observée. Aucune différence concernant les valeurs prédites dans l’optimisation de la conception expérimentale n’a été observée. Les préparations d’émulgel ont montré des valeurs de forces de détachement appropriées et aucune différence significative n’a été observée entre les préparations d’émulgel à base de caféine et les préparations de contrôle. CONCLUSION: la caféine a été administrée avec succès dans cette préparation optimisée d’émulgel bioadhésif, qui a affiché une grande résistance en ce qui concerne la variabilité du procédé. Il n’y a pas eu de changement significatif dans les attributs de qualité critiques après l’incorporation de la substance active et une stabilité prometteuse a été observée pendant au moins un an. Les résultats ont suggéré que l’émulgel optimisé est un système d’administration de bioadhérence topique intéressant pour les applications cosmétiques, y compris les agents de revitalisation de la peau qui ne se trouvent pas dans les préparations de gels.

Background: Mathematical modeling in modified drug release is an important tool that allows predicting the release rate of drugs in their surrounding environment and elucidates the transport mechanisms involved in the process. Objective: The aim of this work was to develop a mathematical model that allows evaluating the release profile of drugs from polymeric carriers in which the swelling phenomenon is present. Methods: Swellable matrices based on ionic complexes of alginic acid or carboxymethylcellulose with ciprofloxacin were prepared and the effect of adding the polymer sodium salt on the swelling process and the drug release was evaluated. Experimental data from the ciprofloxacin release profiles were mathematically adjusted, considering the mechanisms involved in each stage of the release process. Results: A proposed model, named “Dual Release” model, was able to properly fit the experimental data of matrices presenting the swelling phenomenon, characterized by an inflection point in their release profile. This entails applying the extended model of Korsmeyer-Peppas to estimate the percentage of drug released from the first experimental point up to the inflection point and then a model called Lumped until the final time, allowing to adequately represent the complete range of the drug release profile. Different parameters of pharmaceutical relevance were calculated using the proposed model to compare the profiles of the studied matrices. Conclusion: The “Dual Release” model proposed in this article can be used to predict the behavior of complex systems in which different mechanisms are involved in the release process.

The current study is focused on physicochemical characterization and in vitro drug delivery evaluation ofself-organized nanoparticles based on drug-interpolyelectrolyte complexes (DIPEC). The interactionbetween two oppositely charged polymethacrylates, Eudragit® EPO and L100, and four non-steroidalanti-inflammatory drugs, Salicylic Acid, Benzoic Acid, Ketoprofen and Naproxen was studied.DIPEC nanoparticles produce translucent and stable aqueous dispersions where a remarkably highproportion of drug (between 57 and 95%) is condensed with polyelectrolyte (PE) under the form of ionicpairs. They exhibited particle size in the range of 120e198 nm and high positive zeta potential,contributing to physical stability. The sign of zeta potential shifted from positive to negative by changesin composition of DIPEC. Thermal analysis and X-ray diffraction patterns of freeze dried DIPEC showedthe amorphous state of products and the complete interaction of PE and drug. Solid complexes wereeasily redispersed in water yielding nearly the same parameters of fresh dispersions. In vitro releaseexperiments showed that DIPEC nanodispersions behave as drug reservoirs, exhibiting a slow drugrelease rate in water, which significantly increased in simulating physiological fluids, promoted by ionicexchange. They also exhibited a remarkable robustness towards simulated physiological media ofdifferent pH. Fil: Palena, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: García, Mónica Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Manzo, Ruben Hilario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Jimenez Kairuz, Alvaro Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina