Safety and immunogenicity of a synthetic nanoparticle-based, T cell priming peptide vaccine against dengue in healthy adults in Switzerland: a double-blind, randomized, vehicle-controlled, phase 1 study.

BACKGROUND: Vaccines that minimize the risk of vaccine-induced antibody-dependent enhancement and severe dengue are needed to address the global health threat posed by dengue. This study assessed the safety and immunogenicity of a gold nanoparticle (GNP)-based, multi-valent, synthetic peptide dengue vaccine candidate (PepGNP-Dengue), designed to provide protective CD8+ T cell immunity, without inducing antibodies. METHODS: In this randomized, double-blind, vehicle-controlled, phase 1 trial (NCT04935801), healthy naïve individuals aged 18-45 years recruited at the Centre for primary care and public health, Lausanne, Switzerland, were randomly assigned to receive PepGNP-Dengue or comparator (GNP without peptides [vehicle-GNP]). Randomization was stratified into four groups (low dose [LD] and high dose [HD]), allocation was double-blind from participants and investigators. Two doses were administered by intradermal microneedle injection 21 days apart. Primary outcome was safety, secondary outcome immunogenicity. Analysis was by intention-to-treat for safety, intention-to-treat and per protocol for immunogenicity. FINDINGS: 26 participants were enrolled (August-September 2021) to receive PepGNP-Dengue (LD or HD, n = 10 each) or vehicle-GNP (LD or HD, n = 3 each). No vaccine-related serious adverse events occurred. Most (90%) related adverse events were mild; injection site pain and transient discoloration were most frequently reported. Injection site erythema occurred in 58% of participants. As expected, PepGNP-Dengue did not elicit anti-DENV antibodies of significance. Significant increases were observed in specific CD8+ T cells and dengue dextramer+ memory cell subsets in the LD PepGNP-Dengue but not in the HD PepGNP-Dengue or vehicle-GNP groups, specifically PepGNP-activated CD137+CD69+CD8+ T cells (day 90, +0.0318%, 95% CI: 0.0088-0.1723, p = 0.046), differentiated effector memory (TemRA) and central memory (Tcm) CD8+ T cells (day 35, +0.8/105 CD8+, 95% CI: 0.19-5.13, p = 0.014 and +1.34/105 CD8+, 95% CI: 0.1-7.34, p = 0.024, respectively). INTERPRETATION: Results provide proof of concept that a synthetic nanoparticle-based peptide vaccine can successfully induce virus-specific CD8+ T cells. The favourable safety profile and cellular responses observed support further development of PepGNP-Dengue. FUNDING: Emergex Vaccines Holding Limited.

A digital health algorithm to guide antibiotic prescription in pediatric outpatient care: a cluster randomized controlled trial.

Excessive antibiotic use and antimicrobial resistance are major global public health threats. We developed ePOCT+, a digital clinical decision support algorithm in combination with C-reactive protein test, hemoglobin test, pulse oximeter and mentorship, to guide health-care providers in managing acutely sick children under 15 years old. To evaluate the impact of ePOCT+ compared to usual care, we conducted a cluster randomized controlled trial in Tanzanian primary care facilities. Over 11 months, 23,593 consultations were included from 20 ePOCT+ health facilities and 20,713 from 20 usual care facilities. The use of ePOCT+ in intervention facilities resulted in a reduction in the coprimary outcome of antibiotic prescription compared to usual care (23.2% versus 70.1%, adjusted difference -46.4%, 95% confidence interval (CI) -57.6 to -35.2). The coprimary outcome of day 7 clinical failure was noninferior in ePOCT+ facilities compared to usual care facilities (adjusted relative risk 0.97, 95% CI 0.85 to 1.10). There was no difference in the secondary safety outcomes of death and nonreferred secondary hospitalizations by day 7. Using ePOCT+ could help address the urgent problem of antimicrobial resistance by safely reducing antibiotic prescribing. Clinicaltrials.gov Identifier: NCT05144763.

Towards a Swiss health study with human biomonitoring: Learnings from the pilot phase about participation and design.

BACKGROUND: A large-scale national cohort aiming at investigating the health status and determinants in the general population is essential for high-quality public health research and regulatory decision-making. We present the protocol and first results of the pilot phase to a Swiss national cohort aiming at establishing the study procedures, evaluating feasibility, and assessing participation and willingness to participate. METHODS: The pilot phase 2020/21 included 3 components recruited via different channels: a population-based cross-sectional study targeting the adult population (20-69 years) of the Vaud and Bern cantons via personal invitation, a sub-study on selenium in a convenience sample of vegans and vegetarians via non-personal invitation in vegan/vegetarian networks, and a self-selected sample via news promotion (restricted protocol). Along with a participatory approach and participation, we tested the study procedures including online questionnaires, onsite health examination, food intake, physical activity assessments and biosample collection following high-quality standards. RESULTS: The population-based study and the selenium sub-study had 638 (participation rate: 14%) and 109 participants, respectively, both with an over-representation of women. Of altogether 1349 recruited participants over 90% expressed interest in participating to a national health study, over 75% to contribute to medicine progress and help improving others' health, whereas about one third expressed concerns over data protection and data misuse. CONCLUSIONS: Publicly accessible high-quality public health data and human biomonitoring samples were collected. There is high interest of the general population in taking part in a national cohort on health. Challenges reside in achieving a higher participation rate and external validity. For project management clear governance is key.

Carbapenemase-producing Enterobacteriaceae and vancomycin-resistant Enterococcus faecium: The value of a computerized monitoring system to limit their spread.

OBJECTIVE: To quickly implement Infection Prevention and Control measures ("search and isolate" strategy), a computerized monitoring system for carbapenemase-producing Enterobacteriaceae (CPE) and Vancomycin-resistant Enterococcus faecium (VRE) carrier and contact patients has been developed in our hospital since 2014. The objectives were to assess the value of a computerized monitoring system in CPE and VRE management and to evaluate the relevance of extended monitoring of all contact patients. METHODS: Using the data extracted from the computerized system, we conducted a descriptive analysis of CPE and VRE carriers detected from 2004 to 2019 and CPE and VRE extensive contact patients (when hospital stay overlapped with the stay of a carrier in the same unit) from 2014 to 2019. RESULTS: Between 2015 and 2019 (microbiological data only available during this period), 113 CPE and 558 VRE carriers were registered in the database (DB). Among them, 33.9% CPE and 12.8% VRE carriers were infected (p = 0.02). The most frequent infections were urinary tract infections (52.0%), bloodstream infections (20.0%) and pneumonia (16.0%). Close to 8000 (7679) extended contact patients were exposed. Only 26.2% of them were removed from the DB because of appropriate negative post-exposure rectal screenings. No rectal screening was performed in 33.5% of contact patients. Between 2014 and 2019, 16 outbreaks occurred. The proportion of infected carriers differed significantly between outbreaks (index cases) and non-epidemic episodes (50.0% and 20.5% respectively, p = 0.03). The detection system was able to control diffusion in 99.7% of readmissions of known carriers. Among the 360 readmissions detected by the system, only one was involved in an outbreak due to non-compliance with infection control measures. CONCLUSION: Given the low screening completion rate (26.2%) and the low detection rate (1.3%), extended monitoring of contact patients does not seem relevant. After five years of use, the computerized monitoring system has demonstrated its effectiveness in terms of responsiveness and limitation of the spread of multidrug-resistant organisms.

ePOCT+ and the medAL-suite: Development of an electronic clinical decision support algorithm and digital platform for pediatric outpatients in low- and middle-income countries.

Electronic clinical decision support algorithms (CDSAs) have been developed to address high childhood mortality and inappropriate antibiotic prescription by helping clinicians adhere to guidelines. Previously identified challenges of CDSAs include their limited scope, usability, and outdated clinical content. To address these challenges we developed ePOCT+, a CDSA for the care of pediatric outpatients in low- and middle-income settings, and the medical algorithm suite (medAL-suite), a software for the creation and execution of CDSAs. Following the principles of digital development, we aim to describe the process and lessons learnt from the development of ePOCT+ and the medAL-suite. In particular, this work outlines the systematic integrative development process in the design and implementation of these tools required to meet the needs of clinicians to improve uptake and quality of care. We considered the feasibility, acceptability and reliability of clinical signs and symptoms, as well as the diagnostic and prognostic performance of predictors. To assure clinical validity, and appropriateness for the country of implementation the algorithm underwent numerous reviews by clinical experts and health authorities from the implementing countries. The digitalization process involved the creation of medAL-creator, a digital platform which allows clinicians without IT programming skills to easily create the algorithms, and medAL-reader the mobile health (mHealth) application used by clinicians during the consultation. Extensive feasibility tests were done with feedback from end-users of multiple countries to improve the clinical algorithm and medAL-reader software. We hope that the development framework used for developing ePOCT+ will help support the development of other CDSAs, and that the open-source medAL-suite will enable others to easily and independently implement them. Further clinical validation studies are underway in Tanzania, Rwanda, Kenya, Senegal, and India.

[New puff-like disposable electronic cigarettes: expert consensus on their regulation]. / Nouvelles cigarettes électroniques jetables « puffs ¼ : consensus d'expert-e-s sur leur réglementation.

New disposable electronic cigarettes have arrived on the Swiss market since 2020. Our study, conducted according to the three steps of the Delphi fast-track approach developed at Unisanté, obtained a consensual agreement among French-speaking Switzerland experts on the regulation of these products. Ideally, the panel of experts recommends a sales ban of the product. If this is not possible, a number of aspects should be strictly regulated: taxation, product composition and marketing, and sales and consumption restrictions. These regulations should go further than the current European directive and the future Swiss law. The conclusions will be useful to support and guide political decision making from a public health and environmental perspective.

De nouvelles cigarettes électroniques jetables sont arrivées sur le marché suisse depuis 2020. Notre étude, conduite selon les trois étapes de la démarche Delphi fast-track développée à Unisanté, a obtenu un accord consensuel entre expert-e-s suisses romand-e-s sur la réglementation de ces produits. Dans l'idéal, le panel d'expert-e-s recommande une interdiction de vente du produit. Si cela n'est pas possible, certains aspects doivent être strictement réglementés : taxation, composition des produits et marketing, restrictions de vente et de consommation. Ces réglementations devraient aller plus loin que l'actuelle directive européenne et la future loi suisse. Les conclusions seront utiles pour soutenir et orienter la prise de décision politique dans une perspective de santé publique et environnementale.

Determinants of COVID-19 Vaccine Hesitancy During the Pandemic: A Cross-Sectional Survey in the Canton of Vaud, Switzerland.

Objectives: COVID-19 vaccine hesitancy is a major obstacle in the fight against the pandemic. This study aimed to identify the local determinants of vaccine hesitancy in the context of COVID-19 to better inform future immunization campaigns. Methods: The study, conducted in February 2021, included 1,189 randomly selected inhabitants of the canton of Vaud, Switzerland. Online questionnaires investigated determinants of the intention to vaccinate. Previously validated scores (Cronbach's alphas >0.70) were applied to our data for inclusion in the ordinal logistic regression model. Results: Individuals were more likely to vaccinate if they were 40 years or older, wealthy, reported a high educational attainment, or reported comorbidities. Doubts regarding vaccine safety and efficacy, mistrust in authorities and a propensity for natural immunity were identified as the main local hindrances to the COVID-19 vaccination. Conclusion: Outreach to people at risk of severe COVID-19 is particularly relevant in the pandemic context to help mitigate vaccine hesitancy in the canton of Vaud, and should take into consideration the level of education. Further investigation is needed to better understand reasons for mistrust in authorities.

Adherence to Coronavirus Disease 2019 Preventive Measures in a Representative Sample of the Population of the Canton of Vaud, Switzerland.

Objectives: We quantified adherence to COVID-19 preventive measures and explored associated factors, after the first and during the second Swiss epidemic waves. Methods: With an observational cohort study in a representative sample of individuals aged 15 years and more, we analysed the association between self-reported adherence to COVID-19 preventive measures (respect of simple hygiene rules; respect of social distancing rules; wearing a mask) and socio-demographic factors, the existence of a chronic disease, and the existence of a previous confirmed COVID-19 episode. Results: Highest adherence was to simple hygiene rules, followed by social distancing rules and mask wearing, with a slight decrease for simple hygiene rules and a strong increase for mask wearing between visits. Men were significantly less likely to respect simple hygiene rules and wear a mask in public. Participants aged 65 years and more (versus 25-64 years) and those with at least one chronic disease (versus none) were two times more likely to respect social distancing rules and wear a mask. Conclusion: Adherence to social distancing rules and mask wearing was rather poor, especially compared to other countries.

Prevalence of SARS-CoV-2 in Household Members and Other Close Contacts of COVID-19 Cases: A Serologic Study in Canton of Vaud, Switzerland.

BACKGROUND: Research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission within households and other close settings using serological testing is scarce. METHODS: We invited coronavirus disease 2019 (COVID-19) cases diagnosed between February 27 and April 1, 2020, in Canton of Vaud, Switzerland, to participate, along with household members and other close contacts. Anti-SARS-CoV-2 immunoglobulin G antibodies were measured using a Luminex immunoassay. We estimated factors associated with serological status using generalized estimating equations. RESULTS: Overall, 219 cases, 302 household members, and 69 other close contacts participated between May 4 and June 27, 2020. More than half of household members (57.2%; 95% CI, 49.7%-64.3%) had developed a serologic response to SARS-CoV-2, while 19.0% (95% CI, 10.0%-33.2%) of other close contacts were seropositive. After adjusting for individual and household characteristics, infection risk was higher in household members aged ≥65 years than in younger adults (adjusted odds ratio [aOR], 3.63; 95% CI, 1.05-12.60) and in those not strictly adhering to simple hygiene rules like hand washing (aOR, 1.80; 95% CI, 1.02-3.17). The risk was lower when more than 5 people outside home were met during semiconfinement, compared with none (aOR, 0.35; 95% CI, 0.16-0.74). Individual risk of household members to be seropositive was lower in large households (22% less per each additional person). CONCLUSIONS: During semiconfinement, household members of a COVID-19 case were at very high risk of getting infected, 3 times more than close contacts outside home. This highlights the need to provide clear messages on protective measures applicable at home. For elderly couples, who were especially at risk, providing external support for daily basic activities is essential.

Cochleate formulations of Amphotericin b designed for oral administration using a naturally occurring phospholipid.

The purpose of this work was to formulate the poor soluble antifungal and antiparasitic agent Amphotericin B (AmB) in cost-effective lipid-based formulations suitable for oral use in developing countries, overcoming the limitations of poor water solubility, nephrotoxicity and low oral bioavailability. The antifungal agent was formulated, at different molar proportions, in cochleate nanocarriers prepared using an accessible naturally occurring phospholipid rich in phosphatidylserine (Lipoid PSP70). These nanoassemblies were prepared by condensation of negatively charged phospholipid membrane vesicles with divalent cations (Ca2+). Small-angle X-ray scattering studies revealed the Ca2+-triggered condensation of loosely packed multilamellar vesicles into tightly packed bilayers of strongly dehydrated multilamellar organization characterized by narrow Bragg peaks. Transmission electron microscopy and quasi-elastic light scattering studies demonstrated the formation of nanosized particles. AmB drug loading was above 55% in all formulations. Circular dichroism demonstrated the prevalence of monomeric and complexed forms of AmB over toxic aggregates. The stability of AmB in gastric medium was improved by loading in cochleates and its release in gastrointestinal media was retarded. Confocal microscopy studies revealed the in-vitro interactions of Lipoid PSP70-based cochleates with Caco2 intestinal cell monolayers. The results suggest that the low-cost AmB-loaded cochleates may increase the therapeutic range of this drug.

Targeted drug delivery therapies inspired by natural taxes.

A taxis is the movement responding to a stimulus of an organism. This behavior helps organisms to migrate, to find food or to avoid dangers. By mimicking and using natural taxes, many bio-inspired and bio-hybrid drug delivery systems have been synthesized. Under the guidance of physical and chemical stimuli, drug-loaded carriers are led to a target, for example tumors, then locally release the drug, inducing a therapeutic effect without influencing other parts of the body. On the other hand, for moving targets, for example metastasis cancer cells or bacteria, taking advantage of their taxes behavior is a solution to capture and to eliminate them. For instance, several traps and ecological niches have been fabricated to attract cancer cells by releasing chemokines. Cancer cells are then eliminated by drug loaded inside the trap, by radiotherapy focusing on the trap location or by simply removing the trap. Further research is needed to deeply understand the taxis behavior of organisms, which is essential to ameliorate the performance of taxes-inspired drug delivery application.

Nanoscale investigation of human skin and study of skin penetration of Janus nanoparticles.

Janus nanoparticles (JNP) are innovative nanocarriers with an interesting pharmaceutical and cosmetic potential. They are characterized by the presence of a lipid compartment associated with an aqueous compartment delimited by a phospholipid bilayer containing phospholipids and non-ionic surfactants. The hydrodynamic diameter of JNP varies between 150 and 300 nm. The purpose of this study was to answer the following questions: after cutaneous application, are JNP penetrating? If so, how deep? And in which state, intact or degraded? It was essential to understand these phenomena in order to control the rate and kinetics of diffusion of active ingredients, which can be encapsulated in this vehicle for pharmaceutical or cosmetic purposes. An innovative technique called AFM-IR, was used to elucidate the behavior of JNP after cutaneous application. This instrument, coupling atomic force microscopy and IR spectroscopy, allowing to perform chemical analysis at the nanometer scale thanks to local absorption measurements. The identification of organic molecules at the nanoscale is possible without any labelling. Before cutaneous application of JNP, the nano-structure of untreated human skin was investigated with AFM-IR. Then, in vitro human skin penetration of JNP was studied using Franz cells, and AFM-IR allowed us to perform ultra-local information investigations.

ATR-FTIR Characterization of Janus Nanoparticles-Part II: Follow-Up Skin Application.

Attenuated total reflection by Fourier transform infrared (ATR-FTIR) was used to implement reliable infrared descriptors over time of Janus nanoparticles (JNP), to follow their behavior before and after cutaneous application. In the last study, ATR-FTIR spectroscopic analysis allowed us to identify the evolution of intensity ratio of ν(C=O) at 1739 cm-1 and δ(H-O-H) at 1639 cm-1 as a spectroscopic descriptor, for JNP before cutaneous application (on the CaF2 window). This descriptor can be used to follow the physical stability (presence) of nanoparticles over time. The purpose of this study was to understand the behavior of JNP on the surface of the human skin. Therefore, a comparative study with the untreated skin and the skin after cutaneous application of lipophilic phase (Labrafil) of JNP was conducted using Franz cells. The suitability of the ATR-FTIR descriptor of JNP was evaluated, and a research of other descriptors was performed to understand the interaction that may exist between nanoparticles and the skin.

ATR-FTIR Characterization of Janus Nanoparticles. Part I: Implementation of Spectroscopic Descriptors.

The present work deals with original bicompartmental lipid Janus nanoparticles (JNPs), which are characterized by the presence of an oily compartment associated with an aqueous compartment delimited by a phospholipid-based bilayer. The size of JNP varies between 150 and 300 nm. As JNP are promising candidates for cutaneous application, the purpose of this study was to implement reliable infrared descriptors over time of JNP, to follow the physical stability of JNP in open air and over time. Therefore, a comparative study with the nanoemulsion and the physical mixture formulations was conducted by attenuated total reflection by FTIR spectroscopy. We defined herein spectroscopic descriptor reflecting the integrity of the JNP. Principal component analysis and orthogonal partial least square-discriminant analysis were used to validate the relevant descriptor and permitted to extract relevant and useful information from the spectral data. Dynamic light scattering measurements were also carried and gave supporting data for our conclusion on the fate of JNP over time.

A scalable process to produce lipid-based compartmented Janus nanoparticles with pharmaceutically approved excipients.

In the field of nanotechnologies, theranostic approaches and fixed-dose combination products require the development of innovative carriers able to co-encapsulate several entities of interest. This communication describes the preparation and characterization of lipid-based Janus compartmented nanoparticles. They were successfully prepared using a scalable process with pharmaceutically approved excipients. The analysis of the microscopic structure and supramolecular organization demonstrated the formation of two physico-chemically different compartments enabling the co-administration at once of both liposoluble and hydrosoluble active pharmaceutical ingredients.

Effect of high pressure homogenization on the structure and the interfacial and emulsifying properties of ß-lactoglobulin.

The effect of high pressure homogenization (HPH) on the structure of ß-lactoglobulin (ß-lg) was studied by combining spectroscopic, chromatographic, and electrophoretic methods. The consequences of the resulting structure modifications on oil/water (O/W) interfacial properties were also assessed. Moderated HPH treatment (100 MPa/4 cycles) showed no significant modification of protein structure and interfacial properties. However, a harsher HPH treatment (300 MPa/5 cycles) induced structural transformation, mainly from ß-sheets to random coils, wide loss in lipocalin core, and protein aggregation via intermolecular disulfide bridges. HPH-modified ß-lg displayed higher surface hydrophobicity leading to a faster adsorption rate at the interface and an earlier formation of an elastic interfacial film at Cß-lg = 0.1 wt%. However, no modification of the interfacial properties was observed at Cß-lg = 1 wt%. At this protein concentration, the prior denaturation of ß-lg by HPH did not modify the droplet size of nanoemulsions prepared with these ß-lg solutions as the aqueous phases. A slightly increased creaming rate was however observed. The effects of HPH and heat denaturations appeared qualitatively similar, but with differences in their extent.

Erythromycin encapsulation in nanoemulsion-based delivery systems for treatment of Helicobacter pylori infection: Protection and synergy.

Poorly water-soluble and unstable compounds are difficult to develop as drug products using conventional formulation techniques. The aim of the present study was to develop and evaluate a nanoformulation prepared by a hot high-pressure homogenization method, which was a scalable and solvent-free process. We successfully prepared stable nanodispersions to protect a labile antibiotic, erythromycin. The mean diameter of the dispersed droplets was approximately 150 nm, and size distribution was unimodal. Dispersion was physically stable at room temperature for over six months. Using erythromycin as a model compound, we studied its antimicrobial activity in vitro on Helicobacter pylori. Results showed that drug encapsulation improves API stability in an acidic environment and is conducive to a synergistic effect between the drug and the formulation.

Polymorphism of glyceryl behenates: from the individual compounds to the pharmaceutical excipient.

The present paper deals with the crystallization behavior of glyceryl behenate mixtures that are extensively used in the field of drug delivery. The aim of the study was to understand the structural and thermal behaviors of Compritol(®) by considering first the individual polymorphism of the main components constituting this excipient and then their mixtures. This excipient mainly contains dibehenin (∼50%), tribehenin (∼30%) and monobehenin (20%). It appeared clearly that the mixture polymorphism did not result from a simple addition of the individual behavior. Indeed, the solid state organization of this excipient strongly depended on the presence of the third main component, monobehenin, into the mixture. Furthermore, a threshold ratio of monobehenin, at least 10%, must be reach in order to obtain the typical structural organization (co-existence of α/sub-α subcells) and thermal behavior (solid-solid transition and melting) of Compritol(®). This underlines that special attention is required when mixing Compritol(®) with other pharmaceutical ingredients that could trap monoglycerides and modify the equilibrium present in the pure excipient.

Janus nanoparticles: materials, preparation and recent advances in drug delivery.

INTRODUCTION: The term Janus particles was used to describe particles that are the combination of two distinct sides with differences in chemical nature and/or polarity on each face. Due to the exponential growth of interest on multifunctional nanotechnologies, such anisotropic nanoparticles are promising tools in the field of drug delivery. AREAS COVERED: The main preparation processes and the materials used have been described first. Then a specific focus has been done on therapeutic and/or diagnostic applications of Janus particles. EXPERT OPINION: Janus particles are demonstrated as interesting objects with advanced properties that combine features and functionalities of different materials in one single unit. Due to their dual structure, Janus particles are promising candidates for a variety of high-quality applications dealing with drug delivery purposes. Still, the main challenges for the future lie in the development of the preparation of shape-controlled and nano-sized particles with large-scale production processes and approved pharmaceutical excipients.

Controlled release of a highly hydrophilic API from lipid microspheres obtained by prilling: analysis of drug and water diffusion processes with X-ray-based methods.

This study deals with the development of an oral controlled-release dosage form of a highly water-soluble antiepileptic drug. In this respect, drug-loaded spheroid particles close to 380 µm in diameter and composed of lipid binders were prepared by prilling. The purpose here was to thoroughly characterize the controlled-release mechanism of the drug in aqueous pH-6.8 buffered dissolution medium. Water and drug diffusion pathways as well as related kinetic parameters were determined by theoretical analysis of experimental data. Conventional in-vitro experiments performed by analytical high performance liquid chromatography showed that the released fraction reaches 90 wt.% only after a 24-hour immersion in the dissolution medium, pointing out an effective sustained release mechanism. Interpretation of these data was strengthened by the implementation of an innovative methodology involving X-ray diffraction and microtomography to follow the structural evolution of the drug-loaded microspheres at molecular and microscopic scales. This approach allowed to explicit that water and drug transports obey to Fickian diffusion behaviours in good agreement with Crank's and non-simplified Higuchi's equations, respectively. In the latter case, independent modelling of drug release assimilating the microspheres to a variable-geometry reservoir was considered to refine the kinetic analysis of the diffusion process. The water diffusion coefficient D(w) was found equal to 6.3 × 10(-9) cm(2)/s and the API apparent diffusion coefficient reduced to the tortuosity of the matrix D(API)/τ equal to 2 × 10(-9) cm(2)/s. This study ranks among the rare examples of monolithic dispersion device constituted by a highly soluble drug incorporated inside a perfectly inert lipid matrix. The dissolution liquid penetrates the particles through channels progressively created by the solubilization of the drug itself which occurs instantaneously at the inner front of the liquid.