This review aims to provide the state of the art on polymeric and lipid nanoparticles, used or suggested to approach pediatric diseases’ problems and needs, and to inspire new researches in this field. Several drugs are currently not available in formulations suitable for pediatric patients. The United States Pediatric Formulation Initiative suggested applying new technologies to pediatric drug formulations, for instance, nanotechnology. The literature analysis showed that polymeric and lipid nanoparticles have been widely studied to treat pediatric diseases, and albumin nanoparticles and liposomes are already used in clinical practice. Nevertheless, these studies are focused almost exclusively on pediatric cancer treatment. Although nanomedicine may solve many needs of pediatric diseases and medicines, the unavailability of data on pharmacokinetics, safety and efficacy of both drugs and nanoparticles in pediatric patients limits the development of new pediatric medicines based on nanoparticles. Therefore, nanomedicine applied in pediatrics remains a significant challenge in the near future.

Genistein (GEN) is a soy-derived isoflavone that exhibits several biological effects, such as neuroprotective activity and the prevention of several types of cancer and cardiovascular disease. However, due to its poor water solubility and the extensive first-pass metabolism, the oral bioavailability of GEN is limited. In this work, solid lipid nanoparticles (SLN) were developed to preferentially reach the intestinal lymphatic vessels, avoiding the first-pass metabolism of GEN. GEN-loaded SLN were obtained by a hot homogenization process, and the formulation parameters were chosen based on already formulated studies. The nanoparticles were characterized, and the preliminary in vitro chylomicron formation was evaluated. The cell uptake of selected nanocarriers was studied on the Caco-2 cell line and intestinal mucosa. The SLN, characterized by a spherical shape, showed an average diameter (about 280 nm) suitable for an intestinal lymphatic uptake, good stability during the testing time, and high drug loading capacity. Furthermore, the intestinal mucosa and Caco-2 cells were found to uptake SLN. The approximately two-fold increase in particle size suggested a possible interaction between SLN and the lipid components of chylomicrons like phospholipid; therefore, the results may support the potential for these SLN to improve oral GEN bioavailability via intestinal lymphatic absorption.

The role of mycobacterial efflux pumps in drug-resistant tuberculosis has been widely reported. Recently, a new compound, named SS13, has been synthesized, and its activity as a potential efflux inhibitor has been demonstrated. In this work, the chemical–physical properties of the SS13 were investigated; furthermore, a formulative study aimed to develop a formulation suitable for oral administration was performed. SS13 shows nonintrinsic antitubercular activity, but it increases the antitubercular activity of all the tested drugs on several strains. SS13 is insoluble in different simulated gastrointestinal media; thus, its oral absorption could be limited. Solid lipid nanoparticles (SLNs) were, therefore, developed by using two different lipids, Witepsol and/or Gelucire. Nanoparticles, having a particle size (range of 200–450 nm with regards to the formulation composition) suitable for intestinal absorption, are able to load SS13 and to improve its permeation through the intestinal mucosa compared to the pure compound. The cytotoxicity is influenced by the concentration of nanoparticles administered. These promising results support the potential application of these nanocarriers for increasing the oral permeation of SS13 in multidrug-resistant tuberculosis management.

The nose-to-brain delivery route is used to bypass the blood–brain barrier and deliver drugs directly into the brain. Over the years, significant signs of progress have been made in developing nano-drug delivery systems to address the very low drug transfer levels seen with conventional formulations (e.g., nasal solutions). In this paper, sericin nanoparticles were prepared using crocetin as a new bioactive natural cross-linker (NPc) and compared to sericin nanoparticles prepared with glutaraldehyde (NPg). The mean diameter of NPc and NPg was about 248 and 225 nm, respectively, and suitable for nose-to-brain delivery. The morphological investigation revealed that NPc are spherical-like particles with a smooth surface, whereas NPg seem small and rough. NPc remained stable at 4 °C for 28 days, and when freeze-dried with 0.1% w/v of trehalose, the aggregation was prevented. The use of crocetin as a natural cross-linker significantly improved the in vitro ROS-scavenging ability of NPc with respect to NPg. Both formulations were cytocompatible at all the concentrations tested on human fibroblasts and Caco-2 cells and protected them against oxidative stress damage. In detail, for NPc, the concentration of 400 µg/mL resulted in the most promising to maintain the cell metabolic activity of fibroblasts higher than 90%. Overall, the results reported in this paper support the employment of NPc as a nose-to-brain drug delivery system, as the brain targeting of antioxidants is a potential tool for the therapy of neurological diseases.