A review of efficacy and safety of Ugandan anti-malarial plants with application of RITAM score.

BACKGROUND: Malaria, a treatable disease mainly caused by Plasmodium falciparum has remained a health challenge in Africa, a continent that accounted for 96% of total global cases and deaths in 2021. Uganda, a malaria endemic country is experiencing malaria parasite resistance to some of the drugs used in the artemisinin-based combination therapy (ACT). In an effort to prioritize herbal medicines for new product development, this review synthesized the available safety and efficacy literature on the Ugandan anti-malarial plants to suggest most effective herbal plants. METHODS: Literature was exhaustively searched using engines and databases, such as Google scholar, Pubmed, and Scopus-indexed journals during the period of June 2020-December 2021. In the first phase, information on ethnobotanical uses of anti-malarial plants in Uganda was gathered and synthetized to generate a list of plants, followed by data on anti-malarial efficacy (both in vitro and in vivo) on each listed plant. Minimum inhibitory concentrations (µg/ml), and % parasite suppression for every plant were scored using The Research Initiative on Traditional and Antimalarial Methods (RITAM) scoring system. The best twenty (20) plants were evaluated for acute safety (LD50) data in rat model, plant parts used, ease of cultivation, presence of clinical studies and other relevant factors for suggesting the best three (3) plants for future anti-malarial product development. RESULTS: Over one hundred twenty-six (126) plant species are used in Uganda for treatment of malaria in local communities. Out of these, about 33% (41) have been studied for efficacy and safety, with Artemisia annua and Vernonia amygdalina being the most extensively studied and among the best twenty (20) anti-malarial plants in Uganda. Both are limited by parasite recrudescence in clinical studies. Microglossa pyrifolia, a very potent plant (IC50 = 0.03 - 0.05 µg/ml has potential to penetrate the liver and could ameliorate the challenge of recrudescence if combined with A. annua and V. amygdalina in a polyherbal formulation. CONCLUSION: There are many plants with promising potential for malaria treatment in Uganda and a herbal combination of A. annua, V. amydalina and M. pyrifolia could offer the next herbal ACT if carefully studied and developed.

Effects of Autoclaving and Freeze-Drying on Physicochemical Properties of Plectranthus esculentus Starch Derivatives.

The goal of this research was to assess the effects of autoclaving followed by freeze-drying on acetylated xerogel (AXS) and carboxymethylated (CMS) derivatives of Plectranthus esculentus starch as potential vaccine stabilizers. Starch extracted from tubers of P. esculentus were modified by single (carboxymethylation) and dual (acetylation followed by xerogel formation) methods. The derivatives were formulated into vaccine stabilizer suspensions, autoclaved, and freeze-dried without additives or antigen. The derivatives and freeze-dried products were assessed by physical appearance, titration, moisture content (MC), TGA, DSC, XRD, SEM, and FTIR analyses. The degrees of substitution (DS) of the CMS and AXS derivatives were 0.345 and 0.033, respectively. Modification significantly reduced the MC of the derivatives. Freeze-dried AXS (FAXS) had lower MC than freeze-dried CMS (FCMS). The lower degree of hydrophilicity/MC of AXS and FAXS was confirmed by TGA and FTIR band intensities and shifts. Reduction in DSC water desorption/evaporation enthalpies (ΔH) from - 1168.8 mJ (NaS) to - 407.48 mJ (AXS) confirmed the influence of modification on moisture. FTIR confirmed acetylation and carboxymethylation of the derivatives by the presence of 1702.9 cm-1 and 1593 cm-1 bands, respectively (FTIR). Increasing concentrations of the derivatives yielded uncollapsed/unshrunken lyophilisates. SEM and XRD showed that modification, autoclaving, and freeze-drying yielded beehive-like microstructures of FCMS and FAXS that were completely amorphous. Processing (autoclaving and freeze-drying), therefore, enhanced the amorphousness of the starch derivatives which is required in vaccine stability during processing and storage. These findings indicate that these starch derivatives have potential as novel vaccine stabilizers.

Design and Characterization of Metformin-Loaded Solid Lipid Nanoparticles for Colon Cancer.

Colorectal cancer is a global concern, and its treatment is fraught with non-selective effects including adverse side effects requiring hospital visits and palliative care. A relatively safe drug formulated in a bioavailability enhancing and targeting delivery platform will be of significance. Metformin-loaded solid lipid nanoparticles (SLN) were designed, optimized, and characterized for particle size, zeta potential, drug entrapment, structure, crystallinity, thermal behavior, morphology, and drug release. Optimized SLN were 195.01 ± 6.03 nm in size, -17.08 ± 0.95 mV with regard to surface charge, fibrous in shape, largely amorphous, and release of metformin was controlled. The optimized size, charge, and shape suggest the solid lipid nanoparticles will migrate and accumulate in the colon tumor preventing its proliferation and subsequently leading to tumor shrinkage and cell death.

A Co-blended Locust Bean Gum and Polymethacrylate-NaCMC Matrix to Achieve Zero-Order Release via Hydro-Erosive Modulation.

Locust bean gum (LBG) was blended with a cellulose/methacrylate-based interpolyelectrolyte complex (IPEC) to assess the hydro-erosive influence of addition of a polysaccharide on the disposition and drug delivery properties inherent to IPEC matrix. The addition of LBG modulated the drug (levodopa) release characteristics of the IPEC by reducing excessive swelling and preventing bulk erosion. After 8 h in pH 4.5 dissolution medium, gravimetric analysis established that IPEC tablet matrix eroded by 30% of the initial weight due to bulk erosion while LBG-blended IPEC (LBG-b-IPEC) demonstrated surface erosion accounting to 62% of initial weight (596→226.8 mg). Mathematical modeling of the drug release data depicted a transformation from non-Fickian mechanism (IPEC matrices) to zero-order drug release pattern (LBG-b-IPEC matrices) with the linearity of release profile being close to 1 (R (2) = 0.99). Physicochemical characterizations employing Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) explicated that LBG interacted with IPEC by its hydrophilic groups associating with the existing water-holding bodies of IPEC to produce compact matrices. The lattice atomistic modeling elucidated that LBG acted as a linker with the formation of intra- and intermolecular hydrogen bonds generating a highly stabilized polysaccharide-polyelectrolytic structure which influenced the improved properties observed.

Design of an interpolyelectrolyte gastroretentive matrix for the site-specific zero-order delivery of levodopa in Parkinson's disease.

This study focused on developing a gastroretentive drug delivery system employing a triple-mechanism interpolyelectrolyte complex (IPEC) matrix comprising high density, swelling, and bioadhesiveness for the enhanced site-specific zero-order delivery of levodopa in Parkinson's disease. An IPEC was synthesized and directly compressed into a levodopa-loaded matrix employing pharmaceutical technology and evaluated with respect to its physicochemical and physicomechanical properties and in vitro drug release. The IPEC-based matrix displayed superior mechanical properties in terms of matrix hardness (34-39 N/mm) and matrix resilience (44-47%) when different normality's of solvent and blending ratios were employed. Fourier transform infrared spectroscopy confirmed the formation of the IPEC. The formulations exhibited pH and density dependence with desirable gastro-adhesion with Peak Force of Adhesion ranging between 0.15 and 0.21 N/mm, densities from 1.43 to 1.54 g/cm(3) and swellability values of 177-234%. The IPEC-based gastroretentive matrix was capable of providing site-specific levodopa release with zero-order kinetics corroborated by detailed mathematical and molecular modeling studies. Overall, results from this study have shown that the IPEC-based matrix has the potential to improve the absorption and subsequent bioavailability of narrow absorption window drugs, such as levodopa with constant and sustained drug delivery.

Are Bombax buonopozense and Bombax malabaricum possible nutraceuticals for age management?

Human longevity and healthy ageing though controversial require extended investigations. Some studies have shown that ageing can be managed by reducing the amounts of free radicals the cells are exposed to. Oxidative stress has been shown to be combated by antioxidants and plant sources are known to generate antioxidants that are efficacious and low in toxicity. This review aims to enlighten on antioxidants from Bombax buonopozense and Bombax malabaricum for prevention, reversal or delay of age-related diseases. Furthermore, it advocates for more studies to enable the shift from research to commercial applications of the antioxidants as nutraceuticals in age management.

Fabrication, modeling and characterization of multi-crosslinked methacrylate copolymeric nanoparticles for oral drug delivery.

Nanotechnology remains the field to explore in the quest to enhance therapeutic efficacies of existing drugs. Fabrication of a methacrylate copolymer-lipid nanoparticulate (MCN) system was explored in this study for oral drug delivery of levodopa. The nanoparticles were fabricated employing multicrosslinking technology and characterized for particle size, zeta potential, morphology, structural modification, drug entrapment efficiency and in vitro drug release. Chemometric Computational (CC) modeling was conducted to deduce the mechanism of nanoparticle synthesis as well as to corroborate the experimental findings. The CC modeling deduced that the nanoparticles synthesis may have followed the mixed triangular formations or the mixed patterns. They were found to be hollow nanocapsules with a size ranging from 152 nm (methacrylate copolymer) to 321 nm (methacrylate copolymer blend) and a zeta potential range of 15.8-43.3 mV. The nanoparticles were directly compressible and it was found that the desired rate of drug release could be achieved by formulating the nanoparticles as a nanosuspension, and then directly compressing them into tablet matrices or incorporating the nanoparticles directly into polymer tablet matrices. However, sustained release of MCNs was achieved only when it was incorporated into a polymer matrix. The experimental results were well corroborated by the CC modeling. The developed technology may be potentially useful for the fabrication of multi-crosslinked polymer blend nanoparticles for oral drug delivery.

Starch-based xerogels: Effect of acetylation on Physicochemical and rheological properties.

This study was aimed at evaluating the physicochemical and rheological properties of starch-based xerogels. The starch from the shoots of Borassus aethiopium was physically modified by xerogelization, and chemically by acetylation, and combination of acetylation and xerogelization. The solubility, swelling and syneresis of the starches were determined by gravimetric techniques. Evaluation of the native starch and derivatives was done using microscopy, Fourier transform infra-red (FTIR), x-ray diffractometry (XRD), and 1H NMR spectroscopy. Rheological evaluation was done on 10%w/v dispersions using a Bohlin Gemini rheometer (fitted with a 55mm and 2° cone and plate geometry with gap of 70). The diffractograms displayed three peaks, centered on 2θ=15.3, 17.2 and 23.1° for the native and the starch acetate while the xerogel and the starch acetate xerogel were amorphous. The 1H NMR and FTIR confirmed the presence of acetyl groups at about 2.05ppm and 1720cm-1, respectively. Acetylation of the native starch resulted in improvement of solubility. The starch acetate-xerogel sample formed viscoelastic gels without the need for heating. Acetylation and/or xerogelization of the native starch inhibited syneresis. Starch acetate-xerogels, may find application as stabilizer or suspending agent in liquid food and pharmaceutical formulations.

Ex Vivo and In Vivo Characterization of Interpolymeric Blend/Nanoenabled Gastroretentive Levodopa Delivery Systems.

One approach for delivery of narrow absorption window drugs is to formulate gastroretentive drug delivery systems. This study was undertaken to provide insight into in vivo performances of two gastroretentive systems (PXLNET and IPB matrices) in comparison to Madopar® HBS capsules. The pig model was used to assess gastric residence time and pharmacokinetic parameters using blood, cerebrospinal fluid (CSF), and urine samples. Histopathology and cytotoxicity testing were also undertaken. The pharmacokinetic parameters indicated that levodopa was liberated from the drug delivery systems, absorbed, widely distributed, metabolized, and excreted. Cmax were 372.37, 257.02, and 461.28 ng/mL and MRT were 15.36, 14.98, and 13.30 for Madopar HBS capsules, PXLNET, and IPB, respectively. In addition, X-ray imaging indicated that the gastroretentive systems have the potential to reside in the stomach for 7 hours. There was strong in vitro-in vivo correlation for all formulations with r2 values of 0.906, 0.935, and 0.945 for Madopar HBS capsules, PXLNET, and IPB, respectively. Consequently, PXLNET and IPB matrices have pertinent potential as gastroretentive systems for narrow absorption window drugs (e.g., L-dopa) and, in this application specifically, enhanced the central nervous system and/or systemic bioavailability of such drugs.

An optimized gastroretentive nanosystem for the delivery of levodopa.

Characterization of the physicochemical and physicomechanical properties as well as biopharmaceutical suitability of a drug delivery system is needful in optimization of the formulation and manufacturing processes in order to achieve the desired responses. Interpolymeric blend (IPB) nano-enabled gastroretentive levodopa-loaded drug delivery systems were formulated, optimized and characterized using techniques such as spectroscopy, calorimetry, density, textural analysis, morphological analysis, porosity analysis and magnetic resonance imaging. The in vitro drug release of the delivery systems was compared to those of the conventional dosage forms and in vivo absorption was predicted. The average densities were 1.41 mg/mm(3) and 1.56 mg/mm(3) for the two formulations; rigidities were 75.05 N/mm and 84.93 N/mm; and 92% of the pores of the IPB drug delivery system were mesoporous. MR imaging displayed the swollen front at pH 1.5 and the eroded front at pH 4.5. In comparisons to the conventional dosage forms, the IPB nano-enabled gastroretentive levodopa-loaded drug delivery systems exhibited drug release over a prolonged period of time and levodopa-loaded IPB matrices were the best fit for zero-order release. Indeed the analyses of IPB nano-enabled gastroretentive levodopa-loaded drug delivery systems indicate that they hold promise as sustained delivery system for management of Parkinson's disease.

A novel pH-responsive interpolyelectrolyte hydrogel complex for the oral delivery of levodopa. Part II: characterization and formulation of an IPEC-based tablet matrix.

This study was undertaken in order to apply a synthesized interpolyelectrolyte complex (IPEC) of polymethacrylate and carboxymethylcellulose as a controlled release oral tablet matrix for the delivery of the model neuroactive drug levodopa. The IPEC (synthesized in Part I of this work) was characterized by techniques such as Fourier Transform Infra-Red (FTIR) spectroscopy, Differential Scanning Calorimetry (DSC), Advanced DSC (ADSC), and Scanning Electron Microscopy (SEM). The tablet matrices were formulated and characterized for their drug delivery properties and in vitro drug release. FTIR confirmed the interaction between the two polymers. The IPEC composite generated tablet matrices with a hardness ranging from 19.152-27.590 N/mm and a matrix resilience ranging between 42 and 46%. An IPEC of polymethacrylate and carboxymethylcellulose was indeed an improvement on the inherent properties of the native polymers providing a biomaterial with the ability to release poorly soluble drugs such as levodopa at a constant rate over a prolonged period of time.

A novel pH-responsive interpolyelectrolyte hydrogel complex for the oral delivery of levodopa. Part I. IPEC modeling and synthesis.

This study was undertaken to synthesize an interpolyelectrolyte complex (IPEC) of polymethacrylate (E100) and sodium carboxymethylcellulose (NaCMC) to form a polymeric hydrogel material for application in specialized oral drug delivery of sensitive levodopa. Computational modeling was employed to proffer insight into the interactions between the polymers. In addition, the reactional profile of NaCMC and polymethacrylate was elucidated using molecular mechanics energy relationships (MMER) and molecular dynamics simulations (MDS) by exploring the spatial disposition of NaCMC and E100 with respect to each other. Computational modeling revealed that the formation of the IPEC was due to strong ionic associations, hydrogen bonding, and hydrophilic interactions. The computational results corroborated well with the experimental and the analytical data.

Application and Characterization of Gum from Bombax buonopozense Calyxes as an Excipient in Tablet Formulation.

This study was undertaken to explore gum from Bombax buonopozense calyxes as a binding agent in formulation of immediate release dosage forms using wet granulation method. The granules were characterized to assess the flow and compression properties and when compressed, non-compendial and compendial tests were undertaken to assess the tablet properties for tablets prepared with bombax gum in comparison with those prepared with tragacanth and acacia gums. Granules prepared with bombax exhibited good flow and compressible properties with angle of repose 28.60°, Carr's compressibility of 21.30% and Hausner's quotient of 1.27. The tablets were hard, but did not disintegrate after one hour. Furthermore, only 52.5% of paracetamol was released after one hour. The drug release profile followed zero order kinetics. Tablets prepared with bombax gum have the potential to deliver drugs in a controlled manner over a prolonged period at a constant rate.