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The management of brain diseases remains a challenge, particularly because of the difficulty for drugs to cross the blood–brain barrier. Among strategies developed to improve drug delivery, nano-sized emulsions (i.e., nanoemulsions), employed as nanocarriers, have been described. Moreover, focused ultrasound-mediated blood–brain barrier disruption using microbubbles is an attractive method to overcome this barrier, showing promising results in clinical trials. Therefore, nanoemulsions combined with this technology represent a real opportunity to bypass the constraints imposed by the blood–brain barrier and improve the treatment of brain diseases. In this work, a stable freeze-dried emulsion of perfluorooctyl bromide nanodroplets stabilized with home-made fluorinated surfactants able to carry hydrophobic agents is developed. This formulation is biocompatible and droplets composing the emulsion are internalized in multiple cell lines. After intravenous administration in mice, droplets are eliminated from the bloodstream in 24 h (blood half-life (t1/2) = 3.11 h) and no long-term toxicity is expected since they are completely excreted from mice’ bodies after 72 h. In addition, intracerebral accumulation of tagged droplets is safely and significantly increased after focused ultrasound-mediated blood–brain barrier disruption. Thus, the proposed nanoemulsion appears as a promising nanocarrier for a successful focused ultrasound-mediated brain delivery of hydrophobic agents.

Aims There is a crucial need for pharmacokinetic (PK) data on oral vinorelbine (VNR) in the paediatric population. The aim of this work was to assess the PK profile of orally administered VNR in children with recurrent/progressive primary low‐grade glioma (LGG). Methods A multicentre, open‐label, single‐arm intervention phase II study was conducted. Patients, aged between 6 and 18 years, with histologically confirmed recurrent or progressive primary LGG or non‐documented typical optic pathway tumours, were included. PK parameters were estimated by non‐compartmental analysis using Phoenix WinNonlin® software (version 8.0, Certara, Inc.). The influence of demographic and biological covariates on VNR PK parameters was investigated using a multivariate linear regression analysis. Results PK analysis included 36 patients with a median age (range) of 11 (6–17) years. Estimates of apparent oral clearance (CL/F), apparent volume of distribution (V/F), half‐life (t1/2) and their between‐subject variability (CV%) at 60 mg m−2 dose level, were 472 L h−1 (51.8%), 7002 L (57.9%) and 10 h (21.0%), respectively. Negligible accumulation of VNR between C1 and C2 was observed. CL/F and V/F were found to increase with body surface area (BSA) (P = .004). Lower area under the concentration–time curve (AUC) levels were observed among children in comparison to adults. Conclusion Higher doses may be necessary for children with LGG. BSA showed a significant impact on VNR systemic exposure. We believe that our findings will serve as a basis for further studies to better characterize the concentration–response relationships of VNR among paediatric patients.

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