Strategies for the nanoencapsulation of hydrophilic molecules in polymer-based nanoparticles

Hydrophilic drug delivery still remains a challenge; this either being attributed to the fragility and poor cellular penetration of macromolecules, or to the unsuitable pharmacokinetics and toxicity of small drugs, for instance anticancer agents. By offering more favourable pharmacokinetics and protection of the drug, encapsulation in polymer nanoparticles constitutes an attractive possibility to overcome these problems. This review provides an overview of the strategies that have been developed for encapsulating hydrophilic molecules in polymer-containing nanoparticles, e.g. nanospheres and nanocapsules. Polymer nanospheres are loaded either by drug entrapment (by pH modification, use of reverse micelles or the addition of a polyanion) and generally produce a poor level of entrapment efficiency, or molecule sorption onto the nanosphere surface (by pH modification, use of high drug concentration, or ion-pair formation) with the drawbacks of a less-well protected drug from degradation and a faster drug release. Another strategy consists of the use of aqueous-core nanocapsules, generally surrounded by a thin polymer layer, in which hydrophilic molecules are directly solubilised in internal water, and are thus entrapped within the nanocapsule core, assuring drug protection and sustained release. Nanocapsules require less polymer compared to nanospheres; on the other hand, when the drug is entrapped, it has to be added before or during the formulation process, and is thus likely to be degraded. Overall, drug encapsulation in polymer nanoparticles provides a better pharmacokinetic profile and bioavailability, enhanced anticancer activity, reduced drug toxicity and modified drug distribution as compared to free drugs

Reverse micelle-loaded lipid nanocarriers: A novel drug delivery system for the sustained release of doxorubicin hydrochloride

In this study, we are pioneering new nanotechnology for the encapsulation of anticancer drugs (doxorubicin (DOX) and/or docetaxel (DOCE)), whatever their solubility and water affinity. The purpose of this study is to highlight the potential of this recently patented technology, by carrying out a thorough physicochemical characterisation of these multiscaled nanocarriers, followed by the study of an encapsulation and release model of hydrophilic anticancer drug. The formulation process is based on a low-energy nano-emulsification method and allows the generation of a structure composed of oil-based nanocarriers loaded with reverse micelles. Thanks to this, hydrophilic contents can be solubilised in the oily core of this kind of nano-emulsion along with lipophilic content. The results emphasise some original structure particularities due to the multistep formulation process, and the diffusion-based behaviour revealed for the DOX release profile that is shown to be intimately linked to the morphology of the particles

Différences de connectivité effective entre des enfants dyslexiques et des enfants lecteurs normaux pendant une tâche de lecture de pseudomots : une étude par IRMf

International audiencePurpose.—This fMRI study investigated phonological and lexicosemantic processing in dyslexic and in chronological age- and reading level-matched children in a pseudoword reading task.Materials and methods.—The effective connectivity network was compared between the three groups using a structural model including the supramarginal cortex (BA 40; BA: Brodmann area), fusiform cortex (BA 37) and inferior frontal cortex (BA 44/45) areas of the left hemisphere.Results.—The results revealed differences in connectivity patterns. In dyslexic patients, in contrast with chronological age- and reading level-matched groups, no causal relationship was demonstrated between BA 40 and BA 44/45. However, a significant causal relationship was demonstrated between BA 37 and BA 44/45 both in dyslexic children and in the reading levelmatchedgroup.Conclusions.—These findings were interpreted as evidence for a phonological deficit in developmental dyslexiaBut.—Explorer par imagerie fonctionnelle d’activation cérébrale chez l’enfant les aires corticales et les circuits cérébraux impliqués dans le traitement phonologique et lexico sémantique d’une tâche de lecture.Matériel et methods.—Un réseau d’aires cérébrales interconnectées est examiné sur la base d’un modèle structural incluant les cortex supramarginal (aire 40 de Brodmann), fusiforme (aire 37de Brodmann) et frontal inférieur (aires 44/45 de Brodmann) de l’hémisphère gauche. La méthode de modélisation proposée permet d’évaluer une différence de connectivité effective des circuits engagés au cours d’une tâche de lecture de pseudomots entre des enfants dyslexiques et des enfants normaux lecteurs appariés en âge chronologique et lexical.Résultats.—Chez les patients dyslexiques, contrairement aux groupes témoins appariés par l’âge ou le niveau de lecture, aucune interaction causale n’a été démontrée entre les aires 40 et 44/45 de Brodmann qui constituent les noeuds du circuit d’assemblage phonologique. En revanche, une interaction significative a été retrouvée au niveau du circuit d’adressage lexico sémantique, entre les aires 37 et 44/45 de Brodmann, chez les enfants dyslexiques et les enfants appariés par le niveau de lecture.Conclusions.—Ces résultats confirment l’existence d’un déficit des processus phonologiques dans la dyslexie développementale

Anxiety, emotional processing and depression in people with multiple sclerosis.

BACKGROUND: Despite the high comorbidity of anxiety and depression in people with multiple sclerosis (MS), little is known about their inter-relationships. Both involve emotional perturbations and the way in which emotions are processed is likely central to both. The aim of the current study was to explore relationships between the domains of mood, emotional processing and coping and to analyse how anxiety affects coping, emotional processing, emotional balance and depression in people with MS. METHODS: A cross-sectional questionnaire study involving 189 people with MS with a confirmed diagnosis of MS recruited from three French hospitals. Study participants completed a battery of questionnaires encompassing the following domains: i. anxiety and depression (Hospital Anxiety and Depression Scale (HADS)); ii. emotional processing (Emotional Processing Scale (EPS-25)); iii. positive and negative emotions (Positive and Negative Emotionality Scale (EPN-31)); iv. alexithymia (Bermond-Vorst Alexithymia Questionnaire) and v. coping (Coping with Health Injuries and Problems-Neuro (CHIP-Neuro) questionnaire. Relationships between these domains were explored using path analysis. RESULTS: Anxiety was a strong predictor of depression, in both a direct and indirect way, and our model explained 48% of the variance of depression. Gender and functional status (measured by the Expanded Disability Status Scale) played a modest role. Non-depressed people with MS reported high levels of negative emotions and low levels of positive emotions. Anxiety also had an indirect impact on depression via one of the subscales of the Emotional Processing Scale ("Unregulated Emotion") and via negative emotions (EPN-31). CONCLUSIONS: This research confirms that anxiety is a vulnerability factor for depression via both direct and indirect pathways. Anxiety symptoms should therefore be assessed systematically and treated in order to lessen the likelihood of depression symptoms

Cross-cultural validation of a French version of the Emotional Processing Scale (EPS-25)

Introduction: The Emotional Processing Scale (EPS) is a self-report questionnaire consisting of 25 items designed to identify emotional processing styles and impairments. The aim was to develop a French version of the scale and to test its preliminary validity and reliability in French community and clinical samples. Method: After translation and back-translation, a validation study was conducted with 1176 adults [215 from a community sample, 251 undergraduate psychology students, 686 people with a range of physical health conditions (HIV, multiple sclerosis, chronic pain, leukaemia) and 24 people with bipolar disorder hospitalised for depression]. Results: The internal reliability of the French EPS was good, with a Cronbach's alpha of.91. The five-factor structure of the original English version of the scale was closely reproduced. Conclusions: The French EPS demonstrated good reliability and validity. Correlations with other conceptually similar scales (e.g., TAS-20, CERQ, STAXI) were as predicted. EPS scores distinguished between groups (clinical samples vs. a community sample) that would be expected to differ