Research Articles (School of Pharmacy)

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Ferrocene-bisphosphonates hybrid drug molecules: In vitro antibacterial and antifungal, in silico adme, drug-likeness, and molecular docking studies
(Elsevier, 2024) Egieyeh, Samuel; Anusionwu, Chioma; Fonkui, Thierry Youmbi
The design of hybrid molecules is a promising drug development strategy to prepare effective antimicrobial drugs that employ the concept of combination therapy. This strategy combines two therapeutic agents covalently to target different cellular pathways for synergistic effects. Ferrocene-bisphosphonate hybrid compounds, 1–8 were evaluated in vitro for their antibacterial and antifungal activities against selected fungal strains, gram-positive, and gram-negative bacteria. Hybrid compounds, 5, 6, and 8 exhibited significant antibacterial activity against all the bacterial strains than the control, fosfomycin with the lowest MIC value of ≤ 3 against Proteus mirabilis and Klebsiella aerogenes. The antifungal activity of hybrids, 2, 4, 5, and 6 against Penicillum Citrinum and Aspergillus ochraceus was high when compared to the control, nystatin. The lowest MIC values were 107 and 214 µM against Penicillum Citrinum and Aspergillus ochraceus for hybrid 5. The molecular docking studies revealed the inhibition of urease enzymes in Klebsiella aerogenes with a high binding energy of − 3.973 and − 4.645 Kcal/mol, respectively for hybrids 5 and 6. The in silico toxicity revealed the non-toxic effects of the hybrid compounds. The SwissADME parameters of the hybrid molecules further predicted good permeability, water solubility, and oral bioavailability, inability to cross the blood–brain barrier (BBB) and non-inhibition effects on some CYP isoenzymes, suggesting that their biotransformation will not be via the cytochrome isoenzymes. Most of the hybrids, 4–8 were predicted to be P-glycoprotein substrates. The hybrids obeyed Lipinski’s rules with one violation, the Ghose rule, and the Egan rule. These findings indicate that the efficacy of hybrid compounds as promising antimicrobials and future studies are needed.A
Synthesis, characterization, and biological evaluation of coumarin-nitric oxide donor hybrids as anti-tubercular agents
(Elsevier, 2024) Kareem, Afeez I.; Malan, Sarel F.; Kapp, Erika; Shamido, Sean; Joubert, Jacques
This study presents a series of coumarin nitric oxide donor hybrids that were synthesized, and characterized using FT-IR, H NMR, C NMR, and HR-MS techniques. Initial screening for anti-tubercular activity was conducted against Mycolicibacterium smegmatis MC2 155 (M.smeg) under both nutrient-rich and nutrient-poor conditions. Under nutrient-rich conditions, little inhibition was observed. However, four compounds (1e, 2o, 3f, and 5e) demonstrated notable antiproliferative activity under nutrient-poor conditions, with inhibition rates exceeding 95 % at a 50 μM concentration. Subsequent testing of these compounds on Mycobacterium tuberculosis (M.tb) under nutrient-rich conditions showed inhibition rates ranging from 11 % to 37 % at 50 μM. These results indicate that the coumarin nitric oxide donor hybrids are potentially effective in nutrient-limited environments, similar to the intracellular conditions faced by M.tb. In silico cytotoxicity predictions, compared with rifampicin, indicated potentially low toxicity for these compounds. Further optimization and studies are needed to enhance their efficacy under normal conditions, which could lead to the development of new therapeutic strategies against tuberculosis.
Population pharmacokinetics of amodiaquine and piperaquine in African pregnant women with uncomplicated plasmodium falciparum infections
(John Wiley & Sons, 2024) Ding, Junjie; Ravinetto, Raffaella; Hoglund, Richard
Artemisinin-based combination therapy (ACT) is the first-line recommended treatment for uncomplicated malaria. Pharmacokinetic (PK) properties in pregnant women are often based on small studies and need to be confirmed and validated in larger pregnant patient populations. This study aimed to evaluate the PK properties of amodiaquine and its active metabolite, desethylamodiaquine, and piperaquine in women in their second and third trimester of pregnancy with uncomplicated P. falciparum infections. Eligible pregnant women received either artesunate-amodiaquine (200/540 mg daily, n = 771) or dihydroartemisinin-piperaquine (40/960 mg daily, n = 755) for 3 days (NCT00852423). Population PK properties were evaluated using nonlinear mixed-effects modeling, and effect of gestational age and trimester was evaluated as covariates. 1071 amodiaquine and 1087 desethylamodiaquine plasma concentrations, and 976 piperaquine plasma concentrations, were included in the population PK analysis. Amodiaquine concentrations were described accurately with a one-compartment disposition model followed by a two-compartment disposition model of desethylamodiaquine. The relative bioavailability of amodiaquine increased with gestational age (1.25% per week). The predicted exposure to desethylamodiaquine was 2.8%–32.2% higher in pregnant women than that reported in non-pregnant women, while day 7 concentrations were comparable. Piperaquine concentrations were adequately described by a three-compartment disposition model. Neither gestational age nor trimester had significant impact on the PK of piperaquine. The predicted exposure and day 7 concentrations of piperaquine were similar to that reported in non-pregnant women. In conclusion, the exposure to desethylamodiaquine and piperaquine was similar to that in non-pregnant women. Dose adjustment is not warranted for women in their second and their trimester of pregnancy.
Inhalational delivery of β-glucan-chitosan-poly(lactic co-glycolic) acid nanoparticles enhance alveolar macrophage rifampin concentrations for the treatment of tuberculosis
(John Wiley and Sons Inc, 2024) Dube, Admire; Kutscher, Hilliard L.; Chaves, Lee
Despite multiple treatments for tuberculosis (TB), there are ≈10 million new cases and 1.5 million deaths annually, warranting the need for new therapeutics. Major clinical treatment issues include the length of treatment which is associated with patient non-compliance; and poor cellular drug penetration leading to the generation of drug-resistant strains. This study underscores the potential of β-glucan-chitosan (CS) poly(lactic co-glycolic) acid (PLGA) nanoparticles as a promising immunostimulatory adjunct for TB treatment. To facilitate drug delivery to alveolar macrophage, a CS-PLGA nanoparticle is developed containing rifampin in the core with β-glucan as a surface ligand, to stimulate the immune system. Mice are administered a single dose of nanoparticles or free rifampin by oropharyngeal aspiration. Pharmacokinetic investigations reveal sustained release properties of rifampin in vivo, extending over a week. Furthermore, comprehensive analysis indicates stimulation of the innate immune system, as evidenced by cytokine profiling, while concurrently revealing no detrimental effects on the alveolar epithelium, as indicated by histological examination and albumin lung leak assessment. These findings collectively establish a strong foundation for the development of a novel adjuvant immunotherapy approach for TB.
Towards integrated mental health services in low-income and middle-income countries: organisation of primary healthcare providers – a scoping review protocol
(BMJ Publishing Group, 2024) Ward, Kim; Marimwe, Chipiwa; Tanyaradzwa Dube, Lorraine; Parker, Mariam B.
Introduction Mental health conditions constitute a significant percentage of the global burden of disease. A shortfall of mental health specialists and a lack of integration of services in primary care in low-income and middle-income countries (LMICs) contribute towards a mental health treatment gap in excess of 70%. Organising and equipping non-specialist healthcare workers is, therefore, an important strategy for improving access to mental health services in LMICs. This scoping review aims to map literature that addresses the organisation of and support provided to health teams in primary care settings within the context of integrated mental healthcare and as it relates to detection, treatment and referral of mental health conditions. The review will be guided by the ‘Innovative Care for Chronic Conditions’ framework. Methods and analysis This review protocol will employ the methodological framework first developed by Arksey and O’Malley and later advanced by others and will follow the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews guidelines. This process will entail identifying the research questions, locating relevant literature, choosing eligible reports and studies, extracting the data and summarising the results in English-language studies and reports from 2008 to 2023 will be sourced from PubMed, CINAHL, Cochrane Library, PsycARTICLES, Scopus, Web of Science, Academic Search Complete and the WHO website.
Exploring antimycobacterial potential: safety evaluation and active compound isolation from gymnopilus junonius
(Multidisciplinary Digital Publishing Institute (MDPI), 2025) Beukes, Denzil; Lerata, Mookho; Didloff, Jenske
Background/Objectives: Tuberculosis remains a major public health crisis, and it is imperative to search for new antimycobacterial drugs. Natural products, including medicinal macrofungi, have been used as sources for the discovery of pharmaceuticals; however, research on their antimycobacterial activity remains limited. This study aimed to isolate and identify the bioactive compound responsible for antimycobacterial activity, thereby expanding on the limited knowledge regarding the antimicrobial activity and bioactive compounds present in Gymnopilus junonius. Methods: Bioassay-guided fractionation using column chromatography and preparative thin-layer chromatography were employed to isolate the active compound. Antimycobacterial activity against Mycobacterium tuberculosis H37 was assessed using a resazurin microplate assay (REMA). The chemical structure was determined by 1H nuclear magnetic resonance (NMR) spectroscopy, heteronuclear single quantum coherence (HSQC) spectroscopy, heteronuclear multiple bond correlation (HMBC) spectroscopy, and high-resolution electrospray ionization mass (HR-ESI-MS) spectrometry. Transmission electron microscopy (TEM) was used to observe the ultrastructural changes in M. tuberculosis induced by the compound. Cytotoxicity was evaluated in African green monkey kidney cells (Vero), human liver cells (C3A), and zebrafish embryos/larvae. Results: Bioassay-guided fractionation led to the isolation of gymnopilene, which showed inhibitory activity against M. tuberculosis (MIC: 31.25 µg/mL). TEM analysis revealed that treatment with gymnopilene caused ultrastructural damage observed as the disruption and disintegration of the cell wall. While gymnopilene demonstrated cytotoxicity in Vero and C3A cells, no toxicity was observed in zebrafish embryos/larvae for the crude extract. Conclusions: This study highlights that macrofungi, such as G. junonius, could be a valuable resource of bioactive compounds.
Synthesis of immunomodulatory biomimetic lipid polymer hybrid nanoparticles and application of zebrafish larvae in immunomodulation screening
(Elsevier B.V., 2025) Irabin, Aime; Ahmed, Rami; Dube, Admire
Since the antibiotic golden era of the mid-20th century, there have been limited antibiotics approved, while antibiotic resistance continues to escalate disproportionately, outpacing the rate of novel antibiotic discovery. This imbalance poses a serious global health concern, with an estimated annual death toll of 10 million due to antibiotic resistance by 2050. There is a growing interest in immunotherapy as an alternative approach to conventional antibiotics due to its ability to target and stimulate immune system, leveraging its innate ability to self-eradicate pathogens. This study synthesized lipid polymer hybrid nanoparticles (LPHNPs) conjugated with two immunomodulatory agents, namely, curdlan and mycolic acid (MA), as a potential immunotherapy for bacterial infections. LPHNPs were synthesized using lecithin and polycaprolactone (PCL) at a 15 % lipid-to-polymer (w/w) ratio. Additionally, PCL-curdlan copolymer, comprising 15 % w/w curdlan, was successfully synthesized and used to conjugate the LPHNPs with various curdlan concentrations. Furthermore, The LPHNPs were conjugated with varying MA concentrations, with or without curdlan. In-vivo assessment of the immunomodulatory effect of the LPHNPs was conducted using a larval zebrafish model assessing behaviour and immunofluorescence, as indicators of immune stimulation. The data suggests that curdlan exhibits a more complex immunoregulatory role as demonstrated by the countered stimulated behavioural effect while inflammation remained heightened. This work also provides new insights that zebrafish larvae are a valuable screening tool in the development of nanoparticle immunotherapies.
Development, implementation, and evaluation of an innovative clinical trial operations training program for Africa (clinops)
(BioMed Central Ltd, 2025) Whitty, Jeremy; Ejigu, Dawit Asmamaw; Fekadu, Abebaw
Background: Africa’s involvement in clinical trials remains very low. Although the crucial role of training initiatives in building clinical trial capacity in Africa has been documented, current efforts fall short as they lack alignment with local contexts. This study aimed to design, develop, implement, and evaluate an innovative clinical trial operations training program for Africa. Methods: We developed ClinOps, a novel 10-week clinical trial operations training program for study coordinators in Africa to enhance their expertise in four fundamental areas: designing, conducting, managing, and reporting clinical trials. To streamline the learning process, we used cloud-based applications that minimize the need for software installations while maximizing student engagement. VoiceThread facilitated interactive content that could be accessed offline. Moodle, an open-source learning management system, offered a platform for sharing learning tools, mentorship, and rubric-driven competency assessments, including quizzes, forums, tutorials, and group assignments. We utilized Zoom for live tutorials and mentoring as required. Effectiveness of the program was evaluated through quantitative pre- and post-surveys, qualitative end-course evaluations, and a comprehensive monitoring and evaluation framework. The pre- and post-surveys measured changes in trainees’ confidence in clinical trial domains and leadership and coordination skills. End-course evaluations gathered feedback on the course content, organization, technology, and instructional methods. We used Wilcoxon rank test to analyze pre- and post-survey scores and thematic analysis to analyze the qualitative data. Results: In the initial cohort, 88 study coordinators from 19 countries participated, including 56 (64%) females, with 57 (65%) actively employed as study coordinators during the training, and 85 (97%) possessing prior experience in clinical trial roles. Among these, 71 (81%) successfully completed the course, with 69 (97%) also completing the post-course assessment. Post-training scores demonstrated substantial improvement compared to pre-training scores in each competency area, including in designing (pre-post training median score = 3.6 vs. 4.6, median difference = 1.0, 95% CI 0.8–1.1, p < 0.001), managing (pre-posttest median score = 3.4 vs. 4.2, median difference = 0.6, 95% CI 0.4–0.8, p < 0.001), conducting (pre-post training median score = 3.9 vs. 4.7, median difference = 0.9, 95% CI 0.6-1.0, p < 0.001), and reporting (pre-posttest median score = 3.0 vs. 4.5, median difference = 1.0, 95% CI 0.9–1.5, p < 0.001) clinical trials. The monitoring and evaluation data confirm the program’s adherence to training best practices, including alignment with local priorities, country ownership, pedagogic innovation, institutional capacity building, sustainability, and ongoing partnerships. The end-course evaluation reflects participants’ positive feedback on the program’s structure, content, relevance to their current roles, and overall delivery methods. Conclusion: The ClinOps program, designed by experts from academia and product development partners, enhanced participants’ clinical trial competencies. To effectively build clinical trials capacity on the continent, training programs should provide thorough competency development in designing, conducting, managing, and reporting trials.
Immunomodulatory nanoparticles induce autophagy in macrophages and reduce mycobacterium tuberculosis burden in the lungs of mice
(American Chemical Society, 2025) Bekale, Raymonde Bamboukou; Maphasa, Retsepile Ephraim; D’Souza, Sarah
Tuberculosis (TB) is the leading cause of death frominfectious disease. Macrophages are the primary immune respondersand become the primary host cells for the causative agentMycobacterium tuberculosis. Following the uptake of M. tuberculosis,the inherent antimicrobial action of macrophages is dampened,enabling the bacterium to reside within these cells and multiply.Rising resistance of M. tuberculosis to antibiotics has led to theinvestigation of novel approaches for the treatment of TB. Here, wereport a host-directed approach, employing biomimetic Curdlanpoly(lactic-co-glycolic acid) (C-PLGA) nanoparticles (NPs), andexamine autophagy induction in infected macrophages, eradication ofM. tuberculosis and immune modulation in a mouse model. Wedemonstrate that the NPs induce autophagy in M. tuberculosis-infectedmacrophages. Treatment of H37Rv infected C57BL/6 mice with these NPs reduced M. tuberculosis burden in the lungs of mice andmodulated cytokines and chemokines and this work demonstrates that these immunomodulatory NPs are a potential treatmentapproach for TB
Research ethics preparedness during outbreaks and public health emergencies: Focus on community engagement
(SAGE Publications Ltd, 2024) Ravinetto, Raffaella; Adhiambo, Joyce; Kimani, Joshua
Research represents an essential component of the response to infectious disease outbreaks and to other public health emergencies, whether they are localised, of international concern, or global. Research conducted in such contexts also comes with particular ethics challenges, the awareness of which has significantly grown following the Ebola outbreak in West Africa, the Zika outbreak in Latin America and the COVID-19 pandemic. These challenges include the need for implementing meaningful community engagement with the researched communities, not just to build unidirectional trust towards the research team, but to achieve a genuine and mutually respectful partnership before, during and after the research. Here, we describe the real-life experience of 10 well-established research clinics in Nairobi, where a successful experience of community engagement linking prevention and care to research was interrupted during the COVID19 pandemic. We contrast this experience with the concept and processes of community engagement as described in selected scientific manuscripts and guidelines, to formulate some conclusions and recommendations. We contend that more action is needed, from research ethics committees and other key-research stakeholders, to align policies and practices with ethics guidance and with evidence-based recommendations from the academic literature, to achieve meaningful community engagement during emergency research, irrespective of the scale and location of an outbreak or public health crisis. Failure to do so, will aggravate the (postcolonial) asymmetries of power in global health and local systems.
Selenium nanoparticle activity against s. mutans biofilms as a potential treatment alternative for periodontitis
(Multidisciplinary Digital Publishing Institute (MDPI), 2024) Hamman, Naasika; Ramburrun, Poornima; Dube, Admire
The disruption of periodontal biofilms and prevailing antimicrobial resistance issues continue to pose a great challenge to the treatment of periodontitis. Here, we report on selenium nanoparticles (SeNPs) as a treatment alternative for periodontitis by determining their antibiofilm activity against S. mutans biofilms and the potential role of particle size in disrupting biofilms. SeNPs were synthesised via a reduction reaction. Various physicochemical characterisations were conducted on the NPs, including size and shape. The microbroth dilution method was used to conduct the biofilm and antibiofilm assay against S. mutans, which was analysed by absorbance. SeNPs displayed hydrodynamic sizes as low as 46 ± 4 nm at a volume ratio of 1:5 (sodium selenite/ascorbic acid) with good monodispersity and stability. Hydrodynamic sizes of SeNPs after resuspension in tryptic soy broth supplemented with 2.5% sucrose (TSB + 2.5% suc.) and incubated at 37 °C for 24 h, ranged from 112 to 263 nm, while the zeta potential values increased to greater than −11 mV. The biofilm assay indicated that S. mutans are weakly adherent, bordering on moderately adherent biofilm producers. The minimum biofilm inhibitory concentration (MBIC) was identified at 500 µg/mL. At a 1000 µg/mL concentration, SeNPs were able to inhibit S. mutan biofilms up to 99.87 ± 2.41% at a volume ratio of 1:1. No correlation was found between antibiofilm activity and particle size; however, antibiofilm activity was proven to be concentration-dependant.
Microencapsulation techniques in HIV pediatric formulations: advances and future outlook
(John Wiley and Sons Ltd, 2024) Okafor, Nnamdi Ikemefuna
The treatment of human immunodeficiency virus (HIV) in children has persistently been complex and tedious on a global scale. This is because adult and pediatric HIV treatments follow a similar therapeutic approach. Due to the dearth of clinically licensed pediatric antiretroviral drug (ARVD) therapy, children with HIV worldwide are prescribed unlicensed drugs each year. This has triggered likelihood of poor drug adherence, therapeutic failure, and even adverse reactions brought on by a variety of factors, including pill size and quantity, which is the main cause of swallowing difficulties, repeated administration of these various ARVDs, many of which have poor solubility and cause severe side effects in children, and unpalatability of the drug, which is one of the criteria for pediatric formulations. Thus, there is a necessity for investigation into several advanced microencapsulation techniques that could curb these challenges. Microencapsulation techniques have explored in drug delivery for encapsulation and manufacture of different nanoparticles that have shown significant potential in mitigating and surmounting different constraints, such as taste masking, enhanced drug solubility and bioavailability, and production of micronized fine powders for treatment of varying diseases. Nevertheless, the usage of these technologies in HIV pediatric formulations has garnered relatively little attention.
Green synthesis of reduced graphene oxide using persea americana mill. extract: characterization, oxygen reduction reaction and antibacterial application
(Elsevier Ltd, 2024) Zikalala, Nkosingiphile E.; Rami, Ahmed; Azizi, Shohreh
Reduced graphene oxide (rGO) has garnered tremendous attention due to its salient properties that make it applicable in various electrochemical and environmental remediation fields. However, the commonly used chemical method to obtain rGO from graphene oxide (GO) involves toxic chemicals making both the process and product toxic and expensive. In the present work, the suitability of Avocado (Persea americana Mill) seed extract to reduce as-synthesized GO to rGO was investigated fully by optimising the reducing parameters such as the pH, temperature, amount of extract and reduction time. The formation of rGO from GO was confirmed with UV–Vis spectrophotometry (UV–Vis), Fourier Transform Infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), Transmission Electron Microscopy (TEM) and the thermogravimetric analysis (TGA). The optimal conditions for reducing GO with avocado seed extract are pH 8, 100 °C, and 12 h. The average thickness and width for the rGO was 5.55 nm and 11.39 nm accordingly. While GO exhibited a ζ of −29.9.3 mV, the reduced GO possessed a − 38.2 mV. Calculations from the Kotouckey-Levich's equation demonstrated that the obtained rGO can potentially be applied as an oxygen reduction reaction (ORR) catalyst for the generation of hydrogen peroxide since it follows a 2e− pathway mechanism where hydrogen peroxide is generated as an intermediate. Additionally, the avocado seed extract reduced GO demonstrated a slight growth inhibition of methicillin resistant S. aureus (MRSA)
South African actinobacteria: a treasure trove of novel bioactive metabolites for drug discovery
(Academy of Science of South Africa, 2024) Acquah, Kojo Sekyi; Beukes, Denzil Ronwynne
Although South Africa is known as one of the most biodiverse countries in the world, based on its unique plants and animals, microorganisms have received much less attention. Microorganisms in general and actinobacteria in particular are an underexplored source of new medicines. Recent studies have demonstrated the presence of diverse cultivable actinobacteria from various biomes. However, investigations of the natural product diversity associated with these microorganisms are lacking. We hereby present a review of natural products isolated from South African actinobacteria together with their biological activities. Many of these natural products are structurally novel and include compounds belonging to the following classes: anthraquinones, isoflavonoids, ketolides, macrolides, macrolactams, tripeptides and depsipeptides. They show a wide range of biological activities including antibacterial, antifungal, cytotoxic and antitumour activities.
Progress in Pharmacometrics Implementation and Regulatory Integration in Africa: A Systematic Review
(2024) Ndzamba Bonginkosi S’fiso; Egieyehand Samuel; Fasinu Pius
The availability of clinical trial data, advocacy, and increased funding has facilitated the implementation of pharmacometrics in Africa, resulting in the establishment of additional training programs for pharmacometricians. This study conducted a systematic review to evaluate the progress made from the implementation of pharmacometrics in clinical drug development and its adoption into drug approval by regulatory authorities in Africa. We performed a comprehensive literature search using major databases such as PubMed and Google Scholar. The study included articles published until 2024, with no lower cutoff. Articles were excluded if not addressing the research question or of pharmacometrics studies done outside Africa with no collaboration with African researchers (study setting). For the review, a total of 121 articles were included for analysis. Among the reported pharmacometrics approaches, Population pharmacokinetics modeling approaches are the most used (95 (78.5%)). South Africa and Uganda researchers have the most research output in pharmacometrics in Africa (82 (89.1%) and 7 (7.61%), respectively), with the University of Cape Town (South Africa) producing the highest (71 (78.8%)) of all article in Africa. The most studied conditions are TB (43 (35.5%)), HIV (33 (27.3%), TB and HIV (22 (18.2%)), and malaria (12 (9.92%). Pharmacometrics is gaining momentum in Africa, and the progress made since inception will significantly improve the safety and efficacy of therapeutic agents used to treat HIV, TB, and other emerging conditions.
Clinically relevant metallic nanoparticles in tuberculosis diagnosis and therapy
(John Wiley and Sons Inc, 2024) Akinnawo, Christianah Aarinola; Dube, Admire
Globally a significant burden of tuberculosis (TB) is faced, which is difficult to eradicate due to patients' non-adherence, and drug-resistant strains that are spreading at an alarming rate. Novel approaches are required to improve diagnosis and treatment. Metallic nanoparticles (MNPs) have demonstrated potential as sensor probes and in combination therapy, which combines MNPs with antimycobacterial drugs to develop new treatment and theranostic approaches. To strengthen the theoretical foundation toward the clinical application of TB nanomedicine, this review focuses on the properties and effectiveness of therapeutically relevant MNPs. It also elaborates on their antimycobacterial mechanisms. This review aims to analyze the body of literature on the topic, pinpoint important empirical findings, and identify knowledge gaps that can provide a basis for future research endeavors and translation of the technologies. Current data suggest that MNPs are potential systems for efficient diagnosis and treatment although additional pre-clinical and clinical research is needed to bring these technologies to the clinic.
Progress in pharmacometrics implementation and regulatory integration in Africa: A systematic review
(John Wiley and Sons Inc, 2024) Ndzamba, Bonginkosi S'fiso; Egieyeh, Samuel; Fasinu, Pius
The availability of clinical trial data, advocacy, and increased funding has facilitated the implementation of pharmacometrics in Africa, resulting in the establishment of additional training programs for pharmacometricians. This study conducted a systematic review to evaluate the progress made from the implementation of pharmacometrics in clinical drug development and its adoption into drug approval by regulatory authorities in Africa. We performed a comprehensive literature search using major databases such as PubMed and Google Scholar. The study included articles published until 2024, with no lower cutoff. Articles were excluded if not addressing the research question or of pharmacometrics studies done outside Africa with no collaboration with African researchers (study setting). For the review, a total of 121 articles were included for analysis. Among the reported pharmacometrics approaches, Population pharmacokinetics modeling approaches are the most used (95 (78.5%)). South Africa and Uganda researchers have the most research output in pharmacometrics in Africa (82 (89.1%) and 7 (7.61%), respectively), with the University of Cape Town (South Africa) producing the highest (71 (78.8%)) of all article in Africa. The most studied conditions are TB (43 (35.5%)), HIV (33 (27.3%), TB and HIV (22 (18.2%)), and malaria (12 (9.92%). Pharmacometrics is gaining momentum in Africa, and the progress made since inception will significantly improve the safety and efficacy of therapeutic agents used to treat HIV, TB, and other emerging conditions.
Perspectives on systematic capacity building in pharmaceutical regulation for regulators of medical products
(Frontiers Media, 2024) Dube, Admire; Gwaza, Luther; Chemwolo, Andrew
Having a robust, integrated regulatory system is important for ensuring the availability of safe and efficacious medical products of good quality and for protecting public health. However, less than 30% of countries globally have reached the required regulatory maturity level three, with low- and middle-income countries facing challenges in attracting and retaining qualified staff. World Health Organization (WHO) advocates for systematic workforce development, including competency-based education, to address these gaps. We provide perspectives on a systematic approach to capacity building of medicine regulators based on the experience and lessons learnt in developing and piloting the WHO global competency framework for medicine regulators through three scenarios. A systematic approach to capacity building, such as the human performance technology model, can be used to implement the WHO competency framework as part of organizational performance improvement while ensuring that initiatives are well-defined, targeted, and aligned with organizational goals. The competency framework can be used in different contexts, such as improving organization performance for individual regulatory authorities, strengthening regional collaborations, harmonization and reliance on medical products assessment and joint good manufacturing practices inspections of pharmaceutical manufacturers, and developing learning programs for medicine regulators. A competency-based learning approach for regulatory professionals ensures the transfer of learning to the workplace by integrating real-world practices in learning activities and assessments. Further work is required to develop and validate the assessment instruments, apply the competency framework in other contexts, expanding the learning programmes while continuously providing feedback for further refinement of the competency framework and implementation support tools.
Comparative study on the topical and transdermal delivery of diclofenac incorporated in nano-emulsions, nano-emulgels, and a colloidal suspension
(Springer, 2022) Dube, Admire; Louw, Estelle-Vionè; Liebenberg, Wilna
Transdermal delivery of active pharmaceutical ingredients (APIs) can be challenging, since the skin possesses a rate-limiting barrier, which may be overcome when APIs possess certain ideal physicochemical properties. The lack thereof would require that APIs be included in drug delivery vehicles to enhance skin permeation. Hence, diclofenac was incorporated into various drug delivery vehicles (i.e., nano-emulsions, nano-emulgels, and a colloidal suspension containing drug-loaded nanoparticles) to investigate the transdermal delivery thereof, while nano-emulsions and nano-emulgels had varying concentrations of evening primrose oil (EPO). The aim of the study was to compare the topical and transdermal diclofenac delivery from the different types of vehicles and to investigate the influence the different EPO concentrations had on diclofenac delivery. After characterization, membrane release studies were performed (to determine whether the API was successfully released from the vehicle) followed by in vitro skin diffusion studies and tape stripping (to establish whether the vehicles assisted the API in reaching the target site (transdermal delivery)). Lastly, cytotoxicity studies were conducted via methyl thiazolyl tetrazolium (MTT) and neutral red (NR) assays on human keratinocyte (HaCaT) cells. Results showed minimal cytotoxic effects at concentrations equivalent to that which had permeated through the skin, while the membrane release and in vitro skin diffusion studies indicated that the nano-emulsions and the 10% EPO vehicles increased API release and diffusion when compared to the other vehicles. However, the colloidal suspension had the highest concentrations of API within the skin. Hence, all the vehicles were non-toxic and effectively delivered diclofenac through the transdermal route.
The In vitro biological activity of biosynthesized silver nanoparticles produced using mangifera indica stem bark extract and properties of Its pharmaceutical gel formulation
(Springer, 2023) Omoteso, Omobolanle A; Adeyemi, Oluwatosin E; Ajala, Tolulope O
This study reports the production of silver nanoparticles using Mangifera indica stem bark (aqueous and methanol) extracts as capping agents and formulation of pharmaceutical gel loaded with the nanoparticles. The extracts were prepared using standard procedures and utilized in biosynthesizing silver nanoparticles. Biosynthesis was ascertained through colour changes, UV–Visible and FTIR spectroscopy. Antioxidant activity of the extracts and biosynthesized nanoparticles were examined by DPPH method. The antimicrobial evaluation was carried out on Pseudomonas aeruginosa and Staphylococcus aureus. Pharmaceutical gels were produced (F1–F5), and loaded with the nanoparticles. Nanoparticles exhibited maximum absorption under UV–visible spectroscopy between 315 and 320 nm. FTIR spectrum showed that alkene and ester functional groups were conferred on the silver nanoparticles by the extracts used. The nanoparticles demonstrated antimicrobial activity against the organisms, which was significantly higher (p < 0.05) than for extracts and reference drug. The antioxidant capacity was in a concentration-dependent manner but significantly lower (p < 0.05) than that of the reference drug. Formulated gels had acceptable organoleptic profiles, pH range of 6.8–7.1, high viscosity, and pseudoplastic flow patterns. The in vitro release profiles of the gels showed was gradual, with t90 higher than 2 h. The release seemed to be influenced by the viscosity of the gel systems. In addition, the release kinetics of the nanoparticle-loaded gel systems followed Higuchi model with r2 ranging from 0.9958 to 0.9980. Mangifera indica extracts were successfully used as bio-reducing agents in the synthesis of silver nanoparticles. The gel formulations had acceptable physical properties and release profiles.

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