Systematic Review of Chemical Compounds with Immunomodulatory Action Isolated from African Medicinal Plants.

A robust, well-functioning immune system is the cornerstone of good health. Various factors may influence the immune system's effectiveness, potentially leading to immune system failure. This review aims to provide an overview of the structure and action of immunomodulators isolated from African medicinal plants. The research was conducted according to PRISMA guidelines. Full-text access research articles published in English up to December 2023, including plant characteristics, isolated phytochemicals, and immuno-modulatory activities, were screened. The chemical structures of the isolated compounds were generated using ChemDraw® (version 12.0.1076), and convergent and distinctive signaling pathways were highlighted. These phytochemicals with demonstrated immunostimulatory activity include alkaloids (berberine, piperine, magnoflorine), polysaccharides (pectin, glucan, acemannan, CALB-4, GMP90-1), glycosides (syringin, cordifolioside, tinocordiside, aucubin), phenolic compounds (ferulic acid, vanillic acid, eupalitin), flavonoids (curcumin, centaurein, kaempferin, luteolin, guajaverin, etc.), terpenoids (oleanolic acid, ursolic acid, betulinic acid, boswellic acids, corosolic acid, nimbidin, andrographolides). These discussed compounds exert their effects through various mechanisms, targeting the modulation of MAPKs, PI3K-Akt, and NF-kB. These mechanisms can support the traditional use of medicinal plants to treat immune-related diseases. The outcomes of this overview are to provoke structural action optimization, to orient research on particular natural chemicals for managing inflammatory, infectious diseases and cancers, or to boost vaccine immunogenicity.

Sex-dependent vulnerability for Wistar rats model following intranasal instillation with Klebsiella pneumoniae ATCC 43816 causing lobar pneumonia.

BACKGROUND: Klebsiella pneumoniae has become one of the major threats to public health as it causes nosocomial and community-acquired infections like lobar pneumonia. This infection causes acute inflammation in the lung, characterized by the recruitment of polymorphonuclear cells, generating free radicals, and decreasing the endogenous antioxidant balance system. Many experimental studies have focused on the induction, progression and resolution of infection up to its peak, but these documented processes remain highly random and their sex dependence un-elicited. These fluctuations of physiopathological parameters would impact disease progression depending on the animal's model and bacterial strain used. The present study investigated the sex-dependent vulnerability of Wistar rats to K. pneumoniae ATCC 43816 lobar pneumonia induced by the intranasal instillation method. METHODS: Experimental pneumonia was induced by K. pneumoniae ATCC 43816 in male and female Wistar rats following intranasal instillation. The physiopathogenesis of the disease was studied by bacteriological and histopathological exams, histomorphometric analysis of the blood and/or lung tissue, and body weight loss in infected animals. In addition, the overall severity of lesions was determined by the total score obtained by averaging the individual scores from the same group of animals. RESULTS: The K. pneumoniae ATCC 43816 strain showed inoculation dose-, incubation time of the disease- and sex-dependent- differences in its ability to induce lobar pneumonia. Evaluation of different parameters showed that the disease peaked on day 15 post-inoculation, with more pathogenic effects on female rats. This observed sex-dependence difference in Wistar rats was mainly highlighted by the determined lethal dose 50 (LD50), bacterial load count in whole blood and lung tissues, body weight loss, inflammatory granulomas forming and diffuse alveolar damages. The pathogenicity was confirmed by scoring the severity of pathologic lesions of lung tissues. CONCLUSIONS: The results obtained highlighted the gender-dependency in the physiopathogenesis processes of K. pneumoniae ATCC 43816 induced-lobar pneumonia, in Wistar rats. Female Wistar rats' susceptibility is useful in studying pathology and in preclinical trial investigations of new treatments for infectious pneumonia.

Development and optimization of a one step process for the production and sterilization of liposomes using supercritical CO2.

Liposomes are very interesting drug delivery systems for pharmaceutical and therapeutic purposes. However, liposome sterilization as well as their industrial manufacturing remain challenging. Supercritical carbon dioxide is an innovative technology that can potentially overcome these limitations. The aim of this study was to optimize a one-step process for producing and sterilizing liposomes using supercritical CO2. For this purpose, a design of experiment was conducted. The analysis of the experimental design showed that the temperature is the most influential parameter to achieve the sterility assurance level (SAL) required for liposomes (≤10-6). Optimal conditions (80 °C, 240 bar, 30 min) were identified to obtain the fixed critical quality attributes of liposomes. The conditions for preparing and sterilizing empty liposomes of various compositions, as well as liposomes containing the poorly water-soluble drug budesonide, were validated. The results indicate that the liposomes have appropriate physicochemical characteristics for drug delivery, with a size of 200 nm or less and a PdI of 0.35 or less. Additionally, all liposome formulations demonstrated the required SAL and sterility at concentrations of 5 and 45 mM, with high encapsulation efficiency.

Entomotherapy as an alternative treatment for diseases due to Gram-negative bacteria in Burkina Faso.

Insects are known for their harmful effects. However, they also benefit humans, animals, plants, and ecosystems. Its beneficial uses include entomophagy and entomotherapy. This study aimed to evaluate the antibacterial activity of insect extracts against Gram-negative bacteria. Antibacterial activities of thirteen crude extracts of medicinal insects were tested against twelve Gram-negative bacteria by diffusion on agar. Imipenem was used as an antibiotic for positive control. The thirteen extracts acted differently against certain Gram-negative bacteria. The largest inhibition diameter was for extracts of Cirina butyrospermi and Mylabris variabilis against Pseudomonas aeruginosa ATCC27853 and Salmonella enteritidis ATCC13076, respectively. The diameters of inhibition obtained using imipenem against these same bacterial strains were 13.0 ± 0.0 mm and 22 ± 1.0 mm, respectively. The lowest inhibition diameter (7.5 ± 0.0 mm) was obtained using Anopheles gambiae extract against Salmonella Typhimurium ATCC14028. Imipenem was active on all strains tested. The highest values of the index multi-resistance to insect's extracts were reported for Pseudomonas aeruginosa ATCC9027 and Serratia odorifera 652411. Overall, the results of this study confirmed the antibacterial activities of insects used by traditional health practitioners to treat different pathologies. Entomotherapy could be an alternative treatment for certain infectious pathologies caused by gram-negative bacteria.

Phytopharmaceutical practices of traditional health practitioners in Burkina Faso: a cross-sectional study.

BACKGROUND: Traditional health practitioners constitute an important part of the health care system in Burkina Faso, particularly in the supply of traditional herbal medicines. Quality and safety of these medicines rely heavily on practices employed during their traditional development. However, traditional phytopharmaceutical practices are poorly described in Burkina Faso. This study aimed to describe the phytopharmaceutical practices of traditional medicine practitioners in Burkina Faso. METHODS: This was a cross-sectional descriptive ethno-pharmaceutical study, conducted from October 1 to November 30, 2020, among traditional practitioners in four randomly selected health districts: Nongr-Massom (Centre region), Tenkodogo (Centre-East region), Diapaga (East region) and Dafra (Hauts-Bassins region). An anonymous semi-structured face-to-face questionnaire was used to collect socio-demographic data and data on raw materials and finished products. RESULTS: Sixty-seven (67) traditional health practitioners, aged 56 years on average, including a majority of men (72%), participated in the study. Gathering of wild medicinal plants was the main source of raw materials acquisition (51.5%), which were usually leaves (32.3%). These raw materials were usually sun-dried (43.9%) and packaged mostly in plastic bags (37.2%). They were derived from 60 plant species belonging to 33 botanical families. Fabaceae was the most represented family (18.7%) and Khaya senegalensis Juss. (Meliaceae) the most cited plant species (5.2%). The finished products had an average shelf life of 17 months and were usually prepared as a decoction (31.7%) and administered most often orally (71.4%). Gastrointestinal disorders were the main predictable adverse events of the finished products (54%). CONCLUSION: This study showed that THPs have important knowledge in the use of medicinal plants, but several shortcomings are observed in their phytopharmaceutical and plant protection practices. Continuous improvement of these practices, through education and training of traditional health practitioners, is essential for the conservation of plant biodiversity and quality assurance of traditional herbal medicines.

Use of traditional medicines among conventional medicine practitioners in Burkina Faso / Utilisation des médicaments traditionnels chez les praticiens de la médecine conventionnelle au Burkina Faso

INTRODUCTION: The integration of traditional medicine into biomedical health care practice is highly dependent on its acceptability by conventional medical practitioners. Its use by conventional practitioners was previously unknown in Burkina Faso. PURPOSE OF RESEARCH: The purpose of this study was to estimate the prevalence of traditional medicine use and the frequency of occurrence of adverse events associated with this use among conventional medical practitioners in Burkina Faso. RESULTS: The majority of the practitioners surveyed were women (56.1%) and the average age was 39.7±7 years. Nurses (56.1%), midwives (31.4%) and physicians (8.2%) were the most represented professions. The prevalence of the use of traditional medicines in the 12 months preceding the survey was 75.6%. Malaria was the main medical reason for using traditional medicines (28%). The frequency of reported adverse events was 10% and mainly concerned gastrointestinal disorders (78.3%). CONCLUSIONS: The majority of conventional medical practitioners in Burkina Faso use traditional medicines for their health problems. This finding suggests the effective integration of traditional medicine into biomedical health care practice which could benefit from good acceptability by these professionals.

Introduction: L'intégration de la médecine traditionnelle dans le système de santé moderne est fortement dépendante de son acceptabilité par les praticiens de ce système. Leur recours à la médecine traditionnelle était jusque-là méconnu au Burkina Faso. But de l'étude: Le but de cette étude était d'estimer la prévalence de l'utilisation des médicaments traditionnels et la fréquence de survenue des événements indésirables parmi les praticiens de santé conventionnels au Burkina Faso. Résultats: La majorité des praticiens enquêtés étaient des femmes (56,1 %) et l'âge moyen s'établissait à 39,7 ±7 ans. Les infirmiers (56,1 %), les sages-femmes (31,4 %) et les médecins (8,2 %) étaient les professions les plus représentées. La prévalence de l'utilisation de médicaments traditionnels durant les douze mois précédant l'enquête était de 75,6 %. Le paludisme apparaissait comme la principale raison médicale du recours aux médicaments traditionnels (28 %). La fréquence des événements indésirables rapportés s'élevait à 10 % et concernaient principalement des troubles gastro-intestinaux (78,3 %). Conclusions: Les praticiens de la médecine conventionnelle ont largement recours aux médicaments traditionnels. Cela suggère l'intégration effective de la médecine traditionnelle dans la pratique biomédicale des soins et la surveillance des risques associés à cette utilisation.

Preformulation study for the selection of a suitable polymer for the development of ellagic acid-based solid dispersion using hot-melt extrusion.

Ellagic acid is one of the most studied polyphenolic compounds due to its numerous promising therapeutic properties. However, this therapeutic potential remains difficult to exploit owing to its low solubility and low permeability, resulting in low oral bioavailability. In order to allow an effective therapeutic application of EA, it is therefore necessary to develop strategies that sufficiently enhance its solubility, dissolution rate and bioavailability. For this purpose, solid dispersions based on pre-selected polymers such as Eudragit® EPO, Soluplus® and Kollidon® VA 64, with 5% w/w ellagic acid loading were prepared by hot extrusion and characterized by X-ray diffraction, FTIR spectroscopy and in vitro dissolution tests in order to select the most suitable polymer for future investigations. The results showed that Eudragit® EPO was the most promising polymer for ellagic acid solid dispersions development because its extrudates allowed to obtain a solution supersaturated in ellagic acid that was stable for at least 90 min. Moreover, the resulting apparent solubility was 20 times higher than the actual solubility of ellagic acid. The extrudates also showed a high dissolution rate of ellagic acid (96.25% in 15 min), compared to the corresponding physical mixture (6.52% in 15 min) or the pure drug (1.56% in 15 min). Furthermore, increasing the loading rate of ellagic acid up to 12% in extrudates based on this polymer did not negatively influence its release profile through dissolution tests.

Current Status and Challenges of Pharmacovigilance of Traditional Medicines in French-Speaking West African (UEMOA) Countries.

BACKGROUND: West African Economic and Monetary Union (UEMOA) countries are characterised by a high prevalence of informal use of medicinal plants and traditional medicines by their population for health care, requiring the establishment of pharmacovigilance, in order to monitor the associated health risks. However, the state of implementation of pharmacovigilance for traditional medicines in UEMOA countries is not known. OBJECTIVE: This study aimed to assess the state of implementation of pharmacovigilance for traditional medicines in the eight UEMOA countries, describing the relevant community provisions, assessing the integration of traditional medicines monitoring into national pharmacovigilance systems and identifying related national challenges. METHODS: This was a cross-sectional study using questionnaires, conducted between 1 May and 31 August 2022. A face-to-face questionnaire was administered to officials responsible for the issue within UEMOA and the West African Health Organisation (WAHO). A second online questionnaire was specifically sent to the pharmacovigilance focal points of the eight UEMOA countries. Questionnaires were designed using the WHO indicators for pharmacovigilance. The face-to-face questionnaire collected two types of data, namely community policies and regulations on pharmacovigilance and technical and financial support from sub-regional organisations to countries. The online questionnaire sent to countries collected four categories of data on the study issue: structural data, process data, impact data and data on national challenges. RESULTS: As a community provision, WAHO has a harmonised regulatory framework for phytovigilance. The monitoring of traditional medicines is not effectively implemented in the pharmacovigilance systems of UEMOA countries. Only two reports of adverse events due to traditional medicines have so far been recorded in the Union. The countries have neither funding nor sufficient human resources for pharmacovigilance in general. Monitoring of traditional medicines in the unregulated market, training of stakeholders, risk communication, and integration of traditional health practitioners in reporting systems are the main challenges of countries for the development of pharmacovigilance for traditional medicines. CONCLUSION: The effective compliance of WAHO's harmonised phytovigilance regulatory framework by UEMOA countries and addressing the challenges identified by the countries constitute the basis for the development of pharmacovigilance for traditional medicines within UEMOA.

Use of supercritical CO2 for the sterilization of liposomes: Study of the influence of sterilization conditions on the chemical and physical stability of phospholipids and liposomes.

The effects of four potential supercritical carbon dioxide (ScCO2) sterilization conditions on the chemical stability of 9 phospholipids and on the physicochemical characteristics of liposomes consisting of stable phospholipids, as well as their sterilization efficiency were evaluated. These conditions were : C1 (ScCO2/70 °C/150 bar/240 min), C2 (ScCO2/0.25 % water/ 0.15% H2O2/ 0.5% acetic anhydride/38° C/85 bar/45 min), C3 (ScCO2/0.08 % peracetic acid/35° C/104 bar/180 min) and C4 (ScCO2/200 ppm H2O2/40 °C/270 bar/90 min). The results showed for phospholipids, a significant increase in hydrolysis products of 3.77 to 14.50 % and an increase in oxidation index of 6.10 to 430.50 % with unsaturated phospholipids for all tested conditions while with saturated phospholipids, no significant degradation was observed. Concerning the liposome formulation, no change in dispersion color and no phospholipid degradation were observed. However, a decrease in liposome size from 126.90 nm to 111.80 nm, 96.27 nm, 99.60 nm and 109.13 nm and an increase in the PdI from 0.208 to 0.271, 0.233, 0.285, and 0.298 were found with conditions C1, C2, C3 and C4 respectively. For the sterilization efficiency, conditions C1, C2 and C3 achieved the required sterility assurance level (SAL) of 10-6 for liposomes.

Hospital preparations of ethanol-free furosemide oral solutions: Formulation and stability study.

Furosemide is a diuretic frequently used in the therapeutic management of edema associated with cardiac, renal, and hepatic failure and hypertension. However, there are a very low number of pharmaceutical dosage forms containing furosemide that are suitable for children under 6- years old. Therefore, there is a real need to develop hospital preparations, especially in the hospital. Four oral pediatric solutions of furosemide (2 mg/Ml) were formulated. Two of those solutions did not contain ethanol. For each formulation, 12 batches of 1600.0 Ml were prepared and packaged in 250.0 Ml brown glass bottles with polypropylene screw caps. The physicochemical properties (visual appearance, pH, osmolarity, drug content) and microbiological quality of the finished product were determined on the freshly prepared solutions and after 90 days of storage at 30°C/65% RH. The physicochemical and microbiological characteristics of the freshly prepared solutions were within the prescribed specifications. After 90 days of storage at 30°C/65% RH, the solutions containing sucrose and those without ethanol showed a slight decrease in pH and furosemide content of about 2.5%-4.5% (w/w). Despite this slight decrease, the characteristics remained within the prescribed specifications. Based on the stability profile of the ethanol-free solution containing sorbitol, it could be implemented in hospitals for the care of pediatric patients.

In Vitro Antioxidant and Anticancer Properties of Various E. senegalensis Extracts.

Although Erythrina senegalensis is a plant widely used in traditional medicine in sub-Saharan Africa, its biological properties have been poorly investigated to date. We first characterized by conventional reactions the composition of several stem bark extracts and evaluated in acellular and cellular assays their pro- or antioxidant properties supported by their high phenolic and flavonoid content, particularly with the methanolic extract. The pro- or antioxidant effects observed did not correlate with their IC50 concentrations against five cancer cell lines determined by MTT assay. Indeed, the CH2Cl2 extract and its ethyl acetate (EtOAc) subfraction appeared more potent although they harbored lower pro- or antioxidant effects. Nevertheless, at equipotent concentration, both extracts induced ER- and mitochondria-derived vacuoles observed by fluorescent microscopy that further led to non-apoptotic cell death. LC coupled to high resolution MS investigations have been performed to identify chemical compounds of the extracts. These investigations highlighted the presence of compounds formerly isolated from E. senegalensis including senegalensein that could be retrieved only in the EtOAc subfraction but also thirteen other compounds, such as 16:3-Glc-stigmasterol and hexadecanoic acid, whose anticancer properties have been previously reported. Nineteen other compounds remain to be identified. In conclusion, E. senegalensis appeared rich in compounds with antioxidant and anticancer properties, supporting its use in traditional practice and its status as a species of interest for further investigations in anticancer drug research.

Design and Implementation of a Computerized Management System for Adverse Drug Reactions at the Sourô SANOU University Hospital (CHUSS) in Bobo-Dioulasso, Burkina Faso.

Pharmacovigilance is the science and activities related to the detection, evaluation, understanding and prevention of adverse drug reactions or any other possible drug-related problems. In our tropics, this discipline is in an embryonic state. The availability of a management system capable of responding to pharmacovigilance activities is the main objective of our study. The coding was done on the DJANGO Framework. Signal detection was done using the ROR method. We designed three modules which are the notification module, the analysis module and the statistics module. This study has allowed us to launch the basis for a computerization of the pharmacovigilance information system and partly meets our objective. However, it could lead to the integration of the dictionary of adverse effects such as MedDRA as well as the International Classification of Medicines (ATC, EphMRA).

Personal protective equipment wearing in the context of COVID-19 in a hospital in Burkina Faso / Port des équipements de protection individuelle dans le contexte de la COVID-19 dans un centre hospitalier du Burkina Faso

INTRODUCTION: Personal protective equipment (PPE) is used by health care workers to protect themselves and patients from various exposures such as infectious agents. However, the wearing of this equipment is not always optimal, especially in an epidemic context of COVID-19 transmission. AIM OF THE STUDY: The aim of this study, in the specific context of COVID-19, is to contribute to the improvement of PPE wearing practices by health workers. METHODS: This is a descriptive cross-sectional study conducted in 2020 at the Charles De Gaulle Pediatric University Hospital in Burkina Faso. All health workers in the care units and the laboratory were included. Data were collected using an observation grid during the first situation indicating the wearing of PPE. The assessment of the indications for wearing PPE was based on the recommendations of the French Society of Hospital Hygiene and on the technical guide for the prevention and control of healthcare-associated infections in Burkina Faso. RESULTS: Out of 350 targeted agents, 296 were observed. Gowns, masks and gloves were worn in 95.60%, 96.58% and 97.63% of cases respectively. However, PPE such as goggles (1.56%), apron (11.54%), and tunic and pants (46.28%) were poorly used during medical care. CONCLUSION: The practices of health workers with regard to the wearing of certain PPE are still insufficient. A training and awareness program on PPE should be considered to improve patient and staff safety.

Introduction: Les équipements de protection individuelle (EPI) sont utilisés par le personnel de santé dans le cadre des soins pour se protéger et protéger les patients contre les expositions diverses telles que les agents infectieux. Toutefois, le port de ces équipements n'est pas toujours optimal, surtout dans un contexte épidémique de transmission de la COVID-19. But de l'étude: La présente étude vise, dans le contexte spécifique de la COVID-19, à contribuer à l'amélioration des pratiques de port des EPI des agents de santé. Méthodes: Il s'agit d'une étude transversale descriptive conduite en 2020 au centre hospitalier universitaire pédiatrique Charles-de-Gaulle du Burkina Faso. Tous les agents de santé des unités de soins et du laboratoire ont été inclus. Les données ont été recueillies au moyen d'une grille d'observation lors de la première situation indiquant le port d'un EPI. L'appréciation des indications de port des EPI s'est basée sur les recommandations de la Société française d'hygiène hospitalière et sur le Guide technique de prévention et contrôle des infections associées aux soins au Burkina Faso. Résultats: Sur 350 agents ciblés, 296 ont été observés. Le port de la blouse, du masque et des gants était observé respectivement dans 95,60 %, 96,58 % et 97,63 % des cas. Cependant, les EPI tels que les lunettes de protection (1,56 %), le tablier (11,54 %) et la tenue professionnelle composée d'une tunique et d'un pantalon (46,28 %) étaient faiblement utilisés lors des soins médicaux. Conclusion: Les pratiques des agents de santé vis-à-vis du port de certains EPI restent insuffisantes. Un programme de formation et de sensibilisation sur les EPI doit être envisagé afin de renforcer la sécurité des patients et du personnel.

[State of play of the regulation of clinical trials in Mali]. / Etat des lieux de la reglementation des essais cliniques au Mali.

OBJECTIVE: The objective was to take stock of the regulation of clinical trials in Mali. MATERIAL AND METHODS: This was a descriptive cross-sectional study carried out of the September 1 to December 15, 2019. It consisted of a literature search and a survey in research centers, ethics committees and regulatory structures in Mali. RESULTS: In 2019, there were 15 clinical trials authorized and conducted by three research centers, including 12 vaccines and 3 drugs trials all approved by an ethics committee. The legal framework for clinical trials is governed in Mali by two texts, one legislative and the other regulatory. They provide for the authorization, suspension or prohibition of biomedical research by the minister in charge of Health. The shortcomings identified relate to the low recovery and lack of evaluation of pharmacovigilance data, the scarcity of site inspections and especially the absence of a technical committee for regulatory evaluation of files at the Pharmacy and Medicines Department (DPM). CONCLUSION: The strengthening of the legal framework is, more than ever, necessary to ensure the protection of the rights, safety and well-being of research subjects in a context of increasing relocation of clinical trials to our countries.

OBJECTIF: L'objectif était de réaliser l'état des lieux de la réglementation des essais cliniques au Mali. MATÉRIEL ET MÉTHODES: Il s'agissait d'une étude transversale descriptive réalisée du 1er septembre au 15 décembre 2019. Elle a consisté en une recherche documentaire et une enquête de terrain dans les centres de recherche, les comités d'éthique et les structures règlementaires du Mali. RÉSULTATS: En 2019, il y a eu 15 essais cliniques autorisés et réalisés par trois centres de recherche, dont 12 vaccinaux et 3 médicamenteux tous approuvés par un comité d'éthique. Le cadre juridique des essais cliniques est régi au Mali par deux textes dont l'un législatif et l'autre réglementaire. Ils prévoient l'autorisation, la suspension ou l'interdiction de la recherche biomédicale par le ministre en charge de la santé. Les insuffisances recensées sont relatives à la faible remontée et au manque d'évaluation des données de pharmacovigilance, la rareté des inspections des sites et surtout l'absence de comité technique d'évaluation règlementaire des dossiers à la Direction de la Pharmacie et du Médicament (DPM). CONCLUSION: Le renforcement du cadre juridique est, plus que jamais, nécessaire pour assurer la protection des droits, la sécurité et le bien-être des sujets de recherche dans un contexte de délocalisation croissante des essais cliniques vers nos pays.

Etat des lieux de la règlementation des essais cliniques au Mali / State of play of the regulation of clinical trials in Mali

Objectif: L'objectif était de réaliser l'état des lieux de la réglementation des essais cliniques au Mali. Matériel et Méthodes: Il s'agissait d'une étude transversale descriptive réalisée du 1er septembre au 15 décembre 2019. Elle a consisté en une recherche documentaire et une enquête de terrain dans les centres de recherche, les comités d'éthique et les structures règlementaires du Mali. Résultats: En 2019, il y a eu 15 essais cliniques autorisés et réalisés par trois centres de recherche, dont 12 vaccinaux et 3 médicamenteux tous approuvés par un comité d'éthique. Le cadre juridique des essais cliniques est régi au Mali par deux textes dont l'un législatif et l'autre réglementaire. Ils prévoient l'autorisation, la suspension ou l'interdiction de la recherche biomédicale par le ministre en charge de la santé. Les insuffisances recensées sont relatives à la faible remontée et au manque d'évaluation des données de pharmacovigilance, la rareté des inspections des sites et surtout l'absence de comité technique d'évaluation règlementaire des dossiers à la Direction de la Pharmacie et du Médicament (DPM). Conclusion: Le renforcement du cadre juridique est, plus que jamais, nécessaire pour assurer la protection des droits, la sécurité et le bien-être des sujets de recherche dans un contexte de délocalisation croissante des essais cliniques vers nos pays

Objective: The objective was to take stockof the regulation of clinical trials in Mali. Material and Methods: This was a descriptive cross-sectional study carried out of the September 1 to December 15, 2019. It consisted of a literature search and a survey in research centers, ethics committees and regulatory structures in Mali. Results: In 2019, there were 15 clinical trials authorized and conducted by three research centers, including 12 vaccines and 3 drugs trials all approved by an ethics committee. The legal framework for clinical trials is governed in Mali by two texts, one legislative and the other regulatory. They provide for the authorization, suspension or prohibition of biomedical research by the minister in charge of Health. The shortcomings identified relate to the low recovery and lack of evaluation of pharmacovigilance data, the scarcity of site inspections and especially the absence of a technical committee for regulatory evaluation of files at the Pharmacy and Medicines Department (DPM). Conclusion: The strengthening of the legal framework is, more than ever, necessary to ensure the protection of the rights, safety and well-being of research subjects in a context of increasing relocation of clinical trials to our countries

Sterilization methods of liposomes: Drawbacks of conventional methods and perspectives.

Liposomes are targeted drug delivery systems that are of great pharmaceutical and therapeutic interest. Parenteral route is the main way used for liposome administration. In this case, their sterility is a requirement. However, due to the particular sensitivity of liposomes and their tendency to physicochemical alterations, their sterilization remains a real challenge. Conventional sterilization methods such as heat, ethylene oxide, ultraviolet and gamma irradiations are considered as unsuitable for liposome sterilization and the recommended methods for obtaining sterility of liposomes are filtration and aseptic manufacturing. Unfortunately, these recommended methods are not without limitations. This review outlines the difficulties associated with the use of these different classical methods for obtaining liposome sterility. The effects on liposome physicochemical and biopharmaceutical characteristics as well as efficacy, toxicity and practical problems of these sterilization techniques have been discussed. The search for an alternative method being therefore necessary, the applicability of supercritical carbon dioxide (ScCO2) technology, which is nowadays a promising strategy for the sterilization of sensitive products such as liposomes, is also examined. It appears from this analysis that ScCO2 could effectively be an interesting alternative to achieve sterility of liposomes, but for this, sterilization assays including challenge tests and optimization studies are needed.

Physical formulation approaches for improving aqueous solubility and bioavailability of ellagic acid: A review.

Ellagic acid (EA) is a polyphenolic active compound with antimalarial and other promising therapeutic activities. However, its solubility and its permeability are both low (BCS IV). These properties greatly compromise its oral bioavailability and clinical utilizations. To overcome these limitations of the physicochemical parameters, several formulation approaches, including particle size reduction, amorphization and lipid-based formulations, have been used. Although these strategies have not yet led to a clinical application, some of them have resulted in significant improvements in the solubility and bioavailability of EA. This critical review reports and analyses the different formulation approaches used by scientists to improve both the biopharmaceutical properties and the clinical use of EA.

Pharmacokinetic study of intravenously administered artemisinin-loaded surface-decorated amphiphilic γ-cyclodextrin nanoparticles.

Artemisinin and its derivatives are currently recommended by World Health Organization for the treatment of malaria. Severe malaria requires a parenteral administration of artemisinin-based formulations. However, the effective use of artemisinin is limited by the pharmacokinetic characteristics of the drug (low water solubility, poor bioavailability and short half-life). To overcome some of these drawbacks, artemisinin-loaded surface-decorated nanoparticles were prepared by co-nanoprecipitation of γ-cyclodextrin bioesterified with C10 alkyl chains and polyethylene glycol (PEG) derivatives (polysorbate 80 and DMPE-mPEG2000). Using a single dose (1.5 mg kg-1 or 2 mg kg-1) by intravenous administration, we investigated the in vivo pharmacokinetic properties in healthy rats of two types of artemisinin-loaded nanoparticle formulations, namely, nanosphere and nanoreservoir systems versus an ethanolic-aqueous solution of artemisinin as reference. Significantly enhanced pharmacokinetic parameters were obtained with artemisinin-loaded nanoparticles. In comparison to reference formulation, the geometric mean exposures in plasma (AUC0-t) exhibited 2.35 and 3.26-fold increases when artemisinin was loaded in nanoreservoir and nanosphere systems, respectively. Its plasma half-life increased 4.00 and 6.25-fold and its clearance decreased up to 2.5 and 4.72-fold. Artemisinin was successfully administered intravenously by means of surface-decorated amphiphilic γ-cyclodextrin nanostructures and showed a longer elimination half-life with respect to an artemisinin solution in ethanol. Therefore, these systems are likely to provide significant advantages for the intravenous treatment of severe malaria.

Plaidoyer pour un renforcement du système de pharmacovigilance au Burkina Faso.

Large-scale deployment of new medicines has been observed over the last two decades in many Sub-Saharan Africa countries faced with major public health issues such as malaria and HIV/AIDS. However, some of these medicines may be responsible for varying degrees of toxicity, with adverse drug reactions leading to decreased compliance or even discontinuation of treatment. Pharmacovigilance systems therefore had to be set up in these countries, such as in Burkina Faso, West Africa, which initiated the organization of pharmacovigilance activities in 2008. Despite this progress, the systems in place have not yet achieved a sufficient level of performance to deal with drug-related health issues, highlighting the need for further actions. Pharmacovigilance in Burkina Faso can be strengthened at multiple levels: pre-service and in-service training of health workers; the establishment of active surveillance based on sentinel sites; informing the public and raising awareness; and strengthening national coordination.