A call to action: securing an uninterrupted supply of Africa's medical products and technologies post COVID-19.

The COVID-19 pandemic unveiled the vulnerability of many African healthcare systems, amplifying inadequacies and constraints in the supply chain for medical products and technologies on the continent. Disruptions in the global supply chain due to the pandemic resulted in the continent's population of over one billion people grappling with shortages in the supply of essential medicines. The shortages and their consequences set back achievement of Sustainable Development Goals and progress towards universal health coverage. A virtual meeting of global experts in medical products and supply chain identified as urgent the need for Africa to build capacity for a self-reliant public health system. Discussants challenged the governments of African countries to turn the continent from its current import driven economy to a continent of indigenous research and development, local production, and an exporter of its medical products and innovations.

A hybrid computational framework for intelligent inter-continent SARS-CoV-2 sub-strains characterization and prediction.

Whereas accelerated attention beclouded early stages of the coronavirus spread, knowledge of actual pathogenicity and origin of possible sub-strains remained unclear. By harvesting the Global initiative on Sharing All Influenza Data (GISAID) database ( https://www.gisaid.org/ ), between December 2019 and January 15, 2021, a total of 8864 human SARS-CoV-2 complete genome sequences processed by gender, across 6 continents (88 countries) of the world, Antarctica exempt, were analyzed. We hypothesized that data speak for itself and can discern true and explainable patterns of the disease. Identical genome diversity and pattern correlates analysis performed using a hybrid of biotechnology and machine learning methods corroborate the emergence of inter- and intra- SARS-CoV-2 sub-strains transmission and sustain an increase in sub-strains within the various continents, with nucleotide mutations dynamically varying between individuals in close association with the virus as it adapts to its host/environment. Interestingly, some viral sub-strain patterns progressively transformed into new sub-strain clusters indicating varying amino acid, and strong nucleotide association derived from same lineage. A novel cognitive approach to knowledge mining helped the discovery of transmission routes and seamless contact tracing protocol. Our classification results were better than state-of-the-art methods, indicating a more robust system for predicting emerging or new viral sub-strain(s). The results therefore offer explanations for the growing concerns about the virus and its next wave(s). A future direction of this work is a defuzzification of confusable pattern clusters for precise intra-country SARS-CoV-2 sub-strains analytics.

Green Preparation of Citric Acid Crosslinked Starch for Improvement of Physicochemical Properties of Cyperus Starch.

OBJECTIVES: This study was undertaken to assess the properties of Cyperus esculentus tuber starch crosslinked with citric acid from liquid substrates of orange peel derived via the natural solid-state fermentation process; a green approach. MATERIALS AND METHODS: The flow properties of the prepared starches were evaluated using standard methods. Water-holding capacity, swelling capacity, moisture sorption capacity, gelatinization temperature using differential scanning calorimetry, morphology, fourier infrared spectroscopy, and pH of the starches were evaluated. RESULTS: Results showed that the pH of the crosslinked starches were lower (3.39-4.07) than that of the native starch (5.25) and the flow profile was found to improve. The crosslinked starches' water-holding capacity (90.67%-96.69%) were higher, whereas its emulsion capacity (15.33) was similar to that of the native starch (15.33). No change was observed in the morphology of the crosslinked starches' granules. The infrared spectra of the native and crosslinked starches showed identical peaks; however, the enthalpy of gelatinization (ΔHgel) of the crosslinked products were found to differ from that of the native starch. Modified starches show propensity of being exploited as binding agents in food and pharmaceutical industries. CONCLUSION: The green modification process proved to be a valuable addition to the available starch modification processes.

Lophira alata Suppresses Phorbol Ester-Mediated Increase in Cell Growth via Inhibition of Protein Kinase C-α/Akt in Glioblastoma Cells.

BACKGROUND: Medicinal plants serve as sources of compounds used to treat other types of cancers. The root of the plant Lophira alata (Ochnaceae) has been used as a component of traditional herbal decoctions administered to cancer patients in southwestern Nigeria. However, the mechanism of the cytotoxic effects of Lophira alata alone or in the presence of phorbol ester has not been investigated in brain tumor cells. OBJECTIVE: This study aimed to examine the cytotoxic potential of the methanolic fraction of Lophira alata root on malignant glioma invasive cellular growth and survival. METHODS: The methanolic fraction of Lophira alata (LAM) was subjected to high-performance liquid chromatography to determine the fingerprints of the active molecules. The antiproliferative effects of Lophira alata were assessed using the MTT and LDH assays. Protein immunoblots were carried out to test the effects of Lophira alata, alone or in the presence of phorbol ester, on survival signaling pathways, such as Akt, mTOR, and apoptotic markers such as PARP and caspases. RESULTS: The methanolic fraction of Lophira alata (LAM) induced a concentration-dependent and time-dependent decrease in glioma cell proliferation. In addition, LAM attenuated phorbol ester-mediated signaling of downstream targets such as Akt/mTOR. Gene silencing using siRNA targeting PKC-alpha attenuated LAM-mediated downregulation of Akt. In addition, LAM induced both PARP and caspase cleavages. The HPLC fingerprint of the fraction indicates the presence of flavonoids. CONCLUSION: LAM decreases cell proliferation and induces apoptosis in glioma cell lines and thus could serve as a therapeutic molecule in the management of gliomas.

Analgesic, anti-inflammatory, and heme biomineralization inhibitory properties of Entada africana ethanol leaf extract with antiplasmodial activity against Plasmodium falciparum.

BACKGROUND: Entada africana (EA) is a medicinal plant used in West Africa for the treatment of malaria fever, but its efficacy against malaria is yet to be scientifically validated. Our study explores the antimalarial potential of the ethanol leaf extract of EA. METHODS: The antiplasmodial activity of EA against chloroquine-sensitive (HB3) and chloroquine-resistant (FcM29) Plasmodium falciparum was determined as well as its peripheral antinociceptive and anti-inflammatory properties. The effect of the extract on human monocytic (THP-1) cells was recorded as a measure of cytotoxicity, whereas the inhibitory effect on heme detoxification was evaluated as a possible mechanism of antiplasmodial activity. RESULTS: At a concentration of 100 µg/mL, EA was noncytotoxic and displayed moderate antiplasmodial activity against HB3 and FcM29 (IC50=26.36 and 28.86 µg/mL, respectively). It also exhibited concentration-dependent inhibition of synthetic heme (IC50=16 mg/mL). The extract (200 mg/kg body weight) showed significant (p<0.05) inhibition of paw inflammation, and significantly (p<0.01, 0.05) reduced the number of abdominal writhes induced by acetic acid (58.62%-65.51%), which was higher compared to that of diclofenac (50%, p<0.05). CONCLUSIONS: These findings suggest that peripheral antinociceptive effects and parasiticidal activity of EA contribute to its antimalarial properties and it can be further explored as effective therapy against malaria infection.

Identification of sitosteryl glucoside palmitate in a chloroform-derived fraction of Phyllanthus niruri with antiplasmodial and peripheral antinociceptive properties

Objective: To evaluate the antiplasmodial properties of fractions of chloroform portion of Phyllanthus niruri (P. niruri) methanol extract and identify a suitable chemical marker present therein. Methods: Chloroform portion of P. niruri methanol extract was separated from silica gel using gradient systems of hexane, ethylacetate and methanol. The fractions were screened for antiplasmodial activity against Plasmodium falciparum HB3 and FcM29. Fractions with IC

Eudraginated polymer blends: a potential oral controlled drug delivery system for theophylline.

Sustained release (SR) dosage forms enable prolonged and continuous deposition of the drug in the gastrointestinal (GI) tract and improve the bioavailability of medications characterized by a narrow absorption window. In this study, a new strategy is proposed for the development of SR dosage forms for theophylline (TPH). Design of the delivery system was based on a sustained release formulation, with a modified coating technique and swelling features aimed to extend the release time of the drug. Different polymers, such as Carbopol 71G (CP), sodium carboxymethylcellulose (SCMC), ethylcellulose (EC) and their combinations were tried. Prepared matrix tablets were coated with a 5 % (m/m) dispersion of Eudragit (EUD) in order to get the desired sustained release profile over a period of 24 h. Various formulations were evaluated for micromeritic properties, drug concentration and in vitro drug release. It was found that the in vitro drug release rate decreased with increasing the amount of polymer. Coating with EUD resulted in a significant lag phase in the first two hours of dissolution in the acidic pH of simulated gastric fluid (SGF) due to decreased water uptake, and hence decreased driving force for drug release. Release became faster in the alkaline pH of simulated intestinal fluid (SIF) owing to increased solubility of both the coating and matrixing agents. The optimized formulation was subjected to in vivo studies in rabbits and the pharmacokinetic parameters of developed formulations were compared with the commercial (Asmanyl(®)) formulation. Asmanyl(®) tablets showed faster absorption (t(max) 4.0 h) compared to the TPH formulation showing a t(max) value of 8.0 h. The C(max) and AUC values of TPH formulation were significantly (p < 0.05) higher than those for Asmanyl(®), revealing relative bioavailability of about 136.93 %. Our study demonstrated the potential usefulness of eudraginated polymers for the oral delivery of the sparingly soluble drug theophylline.

Physicochemical and binder properties of starch obtained from Cyperus esculentus.

The purpose of this study was to isolate starch from the tubers of Cyperus esculentus L. and evaluate its physicochemical and binder properties. Extraction of starch using sodium metabisulfite yielded 37 g of starch per 100 g of the tubers. Scanning electron microscopy indicated that Cyperus starch consists of oval to elliptical particles with a smooth surface. Cyperus starch demonstrates a narrow particle size distribution with a mean of 8.25 µm. Cyperus starch conforms well to United States Pharmacopeia standards established for widely used starches like maize and potato. The X-ray powder diffraction pattern and moisture sorption profile of Cyperus starch were comparable to that of maize starch. Cyperus starch had lower swelling power than maize and potato starch, indicative of stronger associative forces within the granules. Carr's index and Hausner ratio indicate that Cyperus starch should have comparable flow properties with respect to maize and potato starch. Cyperus starch was employed as binder for the formulation of metronidazole tablets. Formulations containing 5%, 7.5%, and 10% Cyperus starch were compared with those containing 10% potato starch. At 10% binder concentration, the tablets containing Cyperus starch exhibited better hardness and negligible friability as compared with those with potato starch. Although the binder concentration had a significant effect on the disintegration time of the tablets, it did not seem to affect the dissolution profile. These results indicate that Cyperus starch provides excellent binding properties without compromising drug release characteristics and should be explored in pharmaceutical formulations.

Natural antidiabetic compound for the therapeutic management of diabetes mellitus and its drug delivery system.

A single tablet dosage form containing the freeze-dried aqueous leaf extract of Vernonia amygdalina (AD1), suitable for use in the therapeutic management of diabetes mellitus, has been developed. The compaction characteristics of the extract were studied using the Heckel equation. The mechanical properties as well as disintegration and dissolution profile of the compacts were also assessed. The results showed that AD1 exhibited very low densification due to dye filling and addition of filler-binders contributed significantly to their subsequent densification. The tablets produced had good mechanical properties. Of the three filler-binders tested, tablets containing Avicel had the shortest disintegration time of about 5 min, while tablets without any filler-binder had the longest disintegration time of 50 min. Dissolution results (T(90%)) showed that tablets containing Avicel released 100% of the extract in less than 15 min proving to be the most suitable in acute diabetes. The order of dissolution is Avicel > maize starch > lactose > extract. It is concluded that incorporation of Avicel as a filler-binder in AD1 preparation produced tablets of suitable compaction properties and ensured adequate drug release for the therapeutic management of diabetes mellitus.

Extraction and physicochemical characterization of a new polysaccharide obtained from the fresh fruits of abelmoschus esculentus.

This paper is the first multi-scale characterization of the fluidize-dried gum extracted from the fresh fruits of the plant Abelmoschus esculentus. It describes the physical, thermal, sorptional and functional properties of this natural gum. Elemental analysis, scanning electron microscopy (SEM), particle size analysis, X-ray powder diffraction (XPRD), thermo-gravimetric analysis (TGA), differential scanning calorimetry (DSC), fourier transmittance infra red (FT-IR), and nuclear magnetic resonance (NMR) spectroscopy were used to characterize the gum sample. Abelmoschus Esculentus Gum (AEG) had a glass transition temperature (Tg) of 70°C and no melting peak. It showed a 14.91% loss in weight at 195°C. X-ray diffractogram showed numerous broad halos for AEG. Elemental analysis showed that AEG contains 39.5, 7.3, 51.8, and 1.4% carbon, hydrogen, oxygen and nitrogen respectively. The results obtained in this study established the fundamental characteristics of AEG and suggests its potential application in the food, cosmetic and pharmaceutical sectors.

Preparation and standardization of a herbal agent for the therapeutic management of asthma.

This study aims to develop a suitable single tablet dosage form containing a mixture of hot water stem back extracts of Anogeissus leiocarpus and Prosopis africana (AA1), suitable for use in the therapeutic management of asthma. The compaction characteristics of the oven-dried hot water extract (HWE) were studied using the Heckel equation. The mechanical properties as well as disintegration and dissolution profile of the compacts were also assessed. The results showed that AA1 exhibited high densification due to dye filling while the subsequent rearrangement of the granules did not contribute, significantly, to their densification. The granules had enhanced plasticity as shown by the low yield point, Py. The tablets produced from the extract had good mechanical properties, with hardness increasing with compression pressure while the friability decreased. Of the four disintegrants tested, tablets containing Explotab had the shortest disintegration time of 11 min while tablets containing Prosolv had the longest disintegration time of 40 min. The order of disintegrant property is Explotab > Cellactose > Emcocel > Maize starch > Prosolv. Dissolution results (t(90%)) show that tablets containing Explotab released 100% of the drug in 20 min proving to be the most suitable in acute asthma attack. The order of dissolution is Explotab > Cellactose > Maize starch > Prosolv > Emcocel. It is concluded that incorporation of Explotab (10%w/w) as a disintegrant in AA1 preparation produced tablets of suitable compressional properties and ensured adequate drug release for the management of acute asthma.

Oral sustained release tablets of zidovudine using binary blends of natural and synthetic polymers.

Oral sustained release matrix tablets of zidovudine (ZDV) were prepared using different types, proportions and blends of carbopol 71G (C71) and a plant gum obtained from Abelmoschus esculentus (AEG). The effect of various formulation factors like polymer proportion, polymer type and pH of the dissolution medium on the in vitro release of the drug was studied, using the half change technique, in 900 ml of dissolution medium, at 100 rpm. Release kinetics were analyzed using Zero-order, Higuchi's square-root and Ritger-Peppas' empirical equations. In vitro release performance as revealed by the time taken for 70% of the drug to be released (t70%), showed that the release rate decreased with increase in polymer proportion. Matrix tablets containing 10 and 20% AEG were found to exhibit immediate-release characteristics. Matrix tablets containing 30% AEG showed t70% value of 204 min and extended the release up to 5 h, while matrix tablets containing 30% carbopol showed t70% value of 234 min and extended the release up to 6 h. Three blends of AEG and C71 at the ratio of 1:2, 2:1 and 1:3 showed t70% values of 132, 312 and 102 min respectively and extended the release up to 8 h. Mathematical analysis of the release kinetics indicated that the nature of drug release from the matrix tablets followed Fickian and anomalous release. Drug release from matrix tablets of zidovudine containing blends of AEG and C71 demonstrates the advantage of blending a natural and synthetic polymer over single polymer use.

Preparation and evaluation of colon targeted drug delivery systems for albendazole using kneading, extrusion and compaction technology.

Albendazole is an orally administered broad-spectrum benzimidazole anthelmintic used against helminthiasis, hydatid cyst disease and neurocysticercosis. The objectives of this investigation are to develop a sustained release drug delivery system for albendazole, and to target its delivery to colon. Albendazole matrix tablets containing varying proportions of single and binary blends of four polymers; polyacrylic acid (carbopol 971), ethylcellulose (Etcell), eudragit L100-55 (EUD), and sodium carboxymethyl cellulose (CMC) were prepared by a modified wet granulation technique of kneading, extrusion and compaction. In vitro release profiles of albendazole was sequentially determined in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) without enzymes and in rat caecal content medium (RCCM) at 37 degrees C. The in vitro drug release from matrix tablets containing CMC and Etcell as single polymers showed initial burst effect in the first 2 h (>20% and 50% respectively), followed by a slow release in SIF. However, matrix tablets containing polymer blends showed that no appreciable drug release occurred up to 5 h. Drug release from tablets containing polymer blends in the dissolution medium containing rat caecal material suddenly increased to > or =30% after 5 h (RCCM), and reaching up to 90% in 24 h. Albendazole matrix tablets containing carbopol 971, Etcell, EUD, and CMC as single polymers and as blends were formulated for oral use. Drug release from the tablet matrices containing carbopol alone, binary blends of carbopol/Etcell, and CMC/EUD were found to be very slow and dependent on polymer concentration. Matrix tablets containing blends of these polymers formulated using kneading, extrusion and compaction technique could provide sustained drug release and can be utilized in the colonic delivery of albendazole.

Effect of the molecular size of carboxymethylcellulose and some polymers on the sustained release of theophylline from a hydrophilic matrix.

The objective of this study was to investigate the influence of the molecular size of carboxymethylcellulose (cmc) and some hydrophobic polymer additives on the release properties of theophylline from tablet matrices. The cmc matrices were prepared by the conventional wet granulation method. The granules were evaluated for angles of repose, bulk density, compressibility index, and porosity, while the tablets were subjected to hardness, friability and compression tests. All tablet formulations showed acceptable pharmacotechnical properties. Low molecular size cmc (cmc-L) showed the shortest drug release t50% of 27 min, for medium size cmc (cmc-M) it was 55 min and for high molecular size cmc (cmc-H) 200 min. In general, the results showed that the drug release rate decreases with an increase in the molecular size of cmc. All polymer additives, ethylcellulose, cellulose acetate phthalate and Eudragit 1-100 retarded theophylline release from cmc-L and cmc-H, with ethylcellulose having the most pronounced effect on cmc-L. Kinetic studies using Hixson-Crowell and Peppas-Ritger equations showed that different drug release mechanisms were involved in controlling drug dissolution from the tablets. The drug release mechanism was influenced by both the molecular size of cmc and the presence of polymer additives.

Behavioural effects in rodents of methyl angolensate: a triterpenoid isolated from Entandrophragma angolense.

Behavioral effects of methyl angolensate were investigated in mice and rats. Spontaneous motor activity, pentobarbital sleeping time, amphetamine-stereotyped behaviour, exploratory activity and apomorphine-induced climbing studies in mice were evaluated. The results revealed that methyl angolensate reduced spontaneous motor activity in mice, prolonged the duration of pentobarbital sleeping time in rats and attenuated amphetamine-induced stereotype behaviour in rats. Methyl angolensate also decreased exploratory activity in mice and reduced the rate of apomorphine-induced climbing in mice at the doses tested. It is suggested that methyl angolensate possesses some biologically active principles that are sedative in nature.