A physiologically-based pharmacokinetic model for predicting doxorubicin disposition in multiple tissue levels and quantitative toxicity assessment.

Doxorubicin is a widely-used chemotherapeutic drug, however its high toxicity poses a significant challenge for its clinical use. To address this issue, a physiologically-based pharmacokinetic (PBPK) model was implemented to quantitatively assess doxorubicin toxicity at cellular scale. Due to its unique pharmacokinetic behavior (e.g. high volume of distribution and affinity to extra-plasma tissue compartments), we proposed a modified PBPK model structure and developed the model with multispecies extrapolation to compensate for the limitation of obtaining clinical tissue data. Our model predicted the disposition of doxorubicin in multiple tissues including clinical tissue data with an overall absolute average fold error (AAFE) of 2.12. The model's performance was further validated with 8 clinical datasets in combined with intracellular doxorubicin concentration with an average AAFE of 1.98. To assess the potential cellular toxicity, toxicity levels and area under curve (AUC) were defined for different dosing regimens in toxic and non-toxic scenarios. The cellular concentrations of doxorubicin in multiple organ sites associated with commonly observed adverse effects (AEs) were simulated and calculated the AUC for quantitative assessments. Our findings supported the clinical dosing regimen of 75 mg/m2 with a 21-day interval and suggest that slow infusion and separated single high doses may lower the risk of developing AEs from a cellular level, providing valuable insights for the risk assessment of doxorubicin chemotherapy. In conclusion, our work highlights the potential of PBPK modelling to provide quantitative assessments of cellular toxicity and supports the use of clinical dosing regimens to mitigate the risk of adverse effects.

Physicochemical characterization of drug nanocarriers.

Pharmaceutical design has enabled important advances in the prevention, treatment, and diagnosis of diseases. The use of nanotechnology to optimize the delivery of drugs and diagnostic molecules is increasingly receiving attention due to the enhanced efficiency provided by these systems. Understanding the structures of nanocarriers is crucial in elucidating their physical and chemical properties, which greatly influence their behavior in the body at both the molecular and systemic levels. This review was conducted to describe the principles and characteristics of techniques commonly used to elucidate the structures of nanocarriers, with consideration of their size, morphology, surface charge, porosity, crystalline arrangement, and phase. These techniques include X-ray diffraction, small-angle X-ray scattering, dynamic light scattering, zeta potential, polarized light microscopy, transmission electron microscopy, scanning electron microcopy, and porosimetry. Moreover, we describe some of the commonly used nanocarriers (liquid crystals, metal-organic frameworks, silica nanospheres, liposomes, solid lipid nanoparticles, and micelles) and the main aspects of their structures.

Multifunction hexagonal liquid-crystal containing modified surface TiO2 nanoparticles and terpinen-4-ol for controlled release.

Multifunctional products have been developed to combine the benefits of functional components and terpinen-4-ol (TP) delivery systems. In this way, p-toluene sulfonic acid modified titanium dioxide (TiO2) nanoparticles and TP, an antioxidant, have been incorporated in liquid-crystalline formulations for photoprotection and controlled release of the TP, respectively. By X-ray powder diffraction and diffuse reflectance spectroscopy, we noted that using p-toluene sulfonic acid as a surface modifier made it possible to obtain smaller and more transparent TiO2 nanoparticles than those commercially available. The liquid-crystalline formulation containing the inorganic ultraviolet filter was classified as broad-spectrum performance by the absorbance spectroscopy measurements. The formulations containing modified TiO2 nanoparticles and TP were determined to be in the hexagonal phase by polarized light microscopy and small-angle X-ray scattering, which makes possible the controlled released of TP following zero-order kinetics. The developed formulations can control the release of TP. Constant concentrations of the substance have been released per time unit, and the modified TiO2 nanoparticles can act as a transparent inorganic sunscreen.

Inorganic UV filters

Nowadays, concern over skin cancer has been growing more and more, especially in tropical countries where the incidence of UVA/B radiation is higher. The correct use of sunscreen is the most efficient way to prevent the development of this disease. The ingredients of sunscreen can be organic and/or inorganic sun filters. Inorganic filters present some advantages over organic filters, such as photostability, non-irritability and broad spectrum protection. Nevertheless, inorganic filters have a whitening effect in sunscreen formulations owing to the high refractive index, decreasing their esthetic appeal. Many techniques have been developed to overcome this problem and among them, the use of nanotechnology stands out. The estimated amount of nanomaterial in use must increase from 2000 tons in 2004 to a projected 58000 tons in 2020. In this context, this article aims to analyze critically both the different features of the production of inorganic filters (synthesis routes proposed in recent years) and the permeability, the safety and other characteristics of the new generation of inorganic filters.

A preocupação com o câncer de pele hoje em dia vem crescendo cada vez mais principalmente em países tropicais, onde a incidência da radiação UVA/B é maior. O uso correto de protetores solares é a forma mais eficaz de prevenir o aparecimento desta doença. Os ativos utilizados em protetores solares podem ser filtros orgânicos e inorgânicos. Filtros inorgânicos apresentam muitas vantagens em relação aos orgânicos, tais como fotoestabilidade, ausência de irritabilidade e amplo espectro de proteção. Entretanto, em razão de apresentarem alto índice de refração, os ativos inorgânicos conferem aos protetores solares aparência esbranquiçada, diminuindo sua atratividade estética. Muitas alternativas têm sido desenvolvidas no sentido de resolver este problema e dentre elas pode-se destacar o uso da nanotecnologia. Estima-se que o uso de nanomateriais deve crescer das atuais 2000 para 58000 toneladas até 2020. Neste sentido, este trabalho tem como objetivo fazer a análise crítica abordando diferentes aspectos envolvidos tanto na obtenção de protetores solares inorgânicos (rotas de sínteses propostas nos últimos anos) quanto na permeabilidade, na segurança e em outros aspectos relacionados à nova geração de filtros solares inorgânicos.