Chemical Analysis, Antibacterial Activities and Uses of Leaves and Calyces of Hibiscus sabdariffa Grown in Dodoma, Tanzania

Preliminary phytochemical screening of aqueous and ethanolic extracts of Hibiscus sabdariffa grown in Tanzania revealed the presence of secondary metabolites like steroids, tannins, saponins, glycosides, terpenoids, flavonoids along with L-ascorbic acid (vitamin C) and iron(II). Furthermore, both leaves and calyces showed antibacterial activities (agar well diffusion method) against selected bacterial species (Escherichia coli, Staphylococcus aureus, Salmonella typhi and Shigella sonnei), but calyces possessed potent antibacterial activities compared to leaves. The results also supported the claimed traditional uses of this plant. When interrogated during the cross-sectional study in Dodoma region, 54% of the respondents claimed the plant is used to treat anaemia (supposedly as it increases haemoglobin levels), 23% claimed it is used in the preparation of local wine and the remaining respondents stated use in both areas. Furthermore, the intake of H. sabdariffa leaves and calyces on regular basis can boost the immunity system and helps in preventing bacterial and viral infections as the plant is loaded with flavonoids and vitamin C. Thus, the results observed for the plant H. sabdariffa that is grown in Dodoma in small scale for traditional uses, paves a way for consideration of future large scale production of pharmaceutical and neutraceutical products in Tanzania. Keywords: Phytochemical screening, Hibiscus sabdariffa, antibacterial activity, L-ascorbic acid and iron(II

A novel controlled release intravaginal bioadhesive polymeric device

PhD Faculty of Health Sciences, University of the Witwatersrand, 2009.HIV/AIDS was discovered almost a quarter of a century ago and has so far claimed the lives of more than 25 million people worldwide. Developing countries remain disproportionately affected, with sub-Saharan Africa contributing more than two-thirds of infections globally. Sexual transmission is the primary route of HIV/AIDS acquisition, and women bear the greatest burden of this pandemic. We are now at a stage where biotechnological advances are needed that can either cure HIV/AIDS, stimulate the immune system to produce anti-HIV-antibodies by vaccination, or prevent HIV infections. One of these advances has been the development of various microbicides. However, a lack of effective drug delivery systems for these agents has remained as a rate-limiting step towards successful HIV prevention. In an attempt to overcome this problem, this study aimed at designing and developing a novel intravaginal bioadhesive polymeric device (IBPD) as a delivery system to effectively deliver a microbicide {polystyrene sulfonate (PSS)} and antiretroviral (ARV) {3'-azido-3'-deoxythymidine (AZT)} combination to the vagina. The development of a successful intravaginal microbicidal drug delivery system requires the design of a formulation to deliver the microbicide-ARV combination in a safe, effective, and consistent manner. The first step therefore was to undertake extensive preliminary screening studies on various polymeric materials using a one variable at a time (OVAT) approach to find suitable polymers for developing an IBPD. Initially 18 biodegradable and biocompatible polymers were employed to produce 62 formulations that were further screened through the OVAT approach to result in 15 lead formulations. Two major concerns of this study were the attainment of satisfactory residence time of the IBPD in the vagina as well as the ability of the IBPD to contain and release the microbicide-ARV in a controlled manner. Therefore, optimization of the IBPD was based on these two requirements for which proper matrix integrity was a pre-requisite. Artificial neural networks (ANNs), a computational technique that is able to simulate the neurological processing ability of the human brain through mathematical modeling, was employed for optimization. The ANN approach confirmed that 5 of the 18 studied polymers could be suitable for the development of an optimized IBPD. To finally attain good vaginal retention for the developed delivery system, extensive bioadhesivity testing was undertaken on the optimized device. Thorough in vitro and ex vivo bioadhesivity analysis was conducted using physicomechanics and computational structural modeling. Allyl penta erythritolcrosslinked poly acrylic acid (APE-PAA) appeared to contribute most to the bioadhesivity. Apart from being employed as a matrix component, PAA was further used as a coating agent to achieve extended bioadhesivity within the posterior fornix of the vagina. Since prolonged release and suitable permeation of the microbicide-ARV across the vaginal tissue was a critical requirement of this study, the device was designed to provide a controlled and prolonged drug release. Prolonged release for up to 72 days was achieved. Furthermore, the design was constructed to ensure that the released drug could permeate into the vaginal tissue and be retained substantially. This was determined by measuring drug flux through ex-vivo permeation studies using freshly excised pig vaginal tissue in a Franz Diffusion Cell (FDC) apparatus. The ultimate aim of the study was to have the IBPD well accommodated in the vagina for successful prevention of STIs and HIV infection. Achievement of this aim was ensured by undertaking extensive in vivo studies in Large White pig model. The IBPDs were inserted under anaesthesia into the posterior fornix of the vagina, using a novel applicator. To detect the retention of the IBPDs and determine their sequential biodegradation pattern in the vagina, X-ray imaging was employed, using radio-opaque Barium Sulphate (BaSO4). To demonstrate that the developed drug delivery system acted locally and was only minimally absorbed systemically, blood samples were taken from the jugular vein of each pig at pre-determined time intervals and subjected to UPLC analysis. The drug content in the vaginal tissue at the end of the study was also determined. Histopathological evaluation was carried out on vaginal epithelium to access the potential for toxicity of the IBPDs. The drug content analysis revealed that greater amounts of AZT and PSS were retained in the vaginal tissue with relatively small quantities (AZT:17%; PSS:13%) crossing into the systemic circulation. The results from the toxicity studies showed that the IBPDs were safe for use. This suggests that the developed drug delivery system (the IBPD) may be suitable for application in the prevention of STIs and HIV infections

A Review on Composite Liposomal Technologies for Specialized Drug Delivery

The combination of liposomes with polymeric scaffolds could revolutionize the current state of drug delivery technology. Although liposomes have been extensively studied as a promising drug delivery model for bioactive compounds, there still remain major drawbacks for widespread pharmaceutical application. Two approaches for overcoming the factors related to the suboptimal efficacy of liposomes in drug delivery have been suggested. The first entails modifying the liposome surface with functional moieties, while the second involves integration of pre-encapsulated drug-loaded liposomes within depot polymeric scaffolds. This attempts to provide ingenious solutions to the limitations of conventional liposomes such as short plasma half-lives, toxicity, stability, and poor control of drug release over prolonged periods. This review delineates the key advances in composite technologies that merge the concepts of depot polymeric scaffolds with liposome technology to overcome the limitations of conventional liposomes for pharmaceutical applications

Trends in the Molecular Pathogenesis and Clinical Therapeutics of Common Neurodegenerative Disorders

The term neurodegenerative disorders, encompasses a variety of underlying conditions, sporadic and/or familial and are characterized by the persistent loss of neuronal subtypes. These disorders can disrupt molecular pathways, synapses, neuronal subpopulations and local circuits in specific brain regions, as well as higher-order neural networks. Abnormal network activities may result in a vicious cycle, further impairing the integrity and functions of neurons and synapses, for example, through aberrant excitation or inhibition. The most common neurodegenerative disorders are Alzheimer’s disease, Parkinson’s disease, Amyotrophic Lateral Sclerosis and Huntington’s disease. The molecular features of these disorders have been extensively researched and various unique neurotherapeutic interventions have been developed. However, there is an enormous coercion to integrate the existing knowledge in order to intensify the reliability with which neurodegenerative disorders can be diagnosed and treated. The objective of this review article is therefore to assimilate these disorders’ in terms of their neuropathology, neurogenetics, etiology, trends in pharmacological treatment, clinical management, and the use of innovative neurotherapeutic interventions

A Review of the Effect of Processing Variables on the Fabrication of Electrospun Nanofibers for Drug Delivery Applications

Electrospinning is a fast emerging technique for producing ultrafine fibers by utilizing electrostatic repulsive forces. The technique has gathered much attention due to the emergence of nanotechnology that sparked worldwide research interest in nanomaterials for their preparation and application in biomedicine and drug delivery. Electrospinning is a simple, adaptable, cost-effective, and versatile technique for producing nanofibers. For effective and efficient use of the technique, several processing parameters need to be optimized for fabricating polymeric nanofibers. The nanofiber morphology, size, porosity, surface area, and topography can be refined by varying these parameters. Such flexibility and diversity in nanofiber fabrication by electrospinning has broadened the horizons for widespread application of nanofibers in the areas of drug and gene delivery, wound dressing, and tissue engineering. Drug-loaded electrospun nanofibers have been used in implants, transdermal systems, wound dressings, and as devices for aiding the prevention of postsurgical abdominal adhesions and infection. They show great promise for use in drug delivery provided that one can confidently control the processing variables during fabrication. This paper provides a concise incursion into the application of electrospun nanofibers in drug delivery and cites pertinent processing parameters that may influence the performance of the nanofibers when applied to drug delivery

Designed oligomers of cyanovirin-N show enhanced HIV neutralization

Cyanovirin-N (CV-N) is a small, cyanobacterial lectin that neutralizes many enveloped viruses, including human immunodeficiency virus type I (HIV-1). This antiviral activity is attributed to two homologous carbohydrate binding sites that specifically bind high mannose glycosylation present on envelope glycoproteins such as HIV-1 gp120. We created obligate CV-N oligomers to determine whether increasing the number of binding sites has an effect on viral neutralization. A tandem repeat of two CV-N molecules (CVN_2) increased HIV-1 neutralization activity by up to 18-fold compared to wild-type CV-N. In addition, the CVN_2 variants showed extensive cross-clade reactivity and were often more potent than broadly neutralizing anti-HIV antibodies. The improvement in activity and broad cross-strain HIV neutralization exhibited by these molecules holds promise for the future therapeutic utility of these and other engineered CV-N variants

Oral Drug Delivery Systems Comprising Altered Geometric Configurations for Controlled Drug Delivery

Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments

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

The antiviral protein cyanovirin-N: the current state of its production and applications.

Human immunodeficiency virus (HIV)/AIDS continues to spread worldwide, and most of the HIV-infected people living in developing countries have little or no access to highly active antiretroviral therapy. The development of efficient and low-cost microbicides to prevent sexual transmission of HIV should be given high priority because there is no vaccine available yet. Cyanovirin-N (CVN) is an entry inhibitor of HIV and many other viruses, and it represents a new generation of microbicide that has specific and potent activity, a different mechanism of action, and unusual chemicophysical stability. In vitro and in vivo antiviral tests suggested that the anti-HIV effect of CVN is stronger than a well-known gp120-targeted antibody (2G12) and another microbicide candidate, PRO2000. CVN is a cyanobacteria-derived protein that has special structural features, making the artificial production of this protein very difficult. In order to develop an efficient and relatively low-cost approach for large-scale production of recombinant CVN to satisfy medical use, this protein has been expressed in many systems by trial and error. Here, to summarize the potential and remaining challenges for the development of this protein into an HIV prevention agent, the progress in the structural mechanism determination, heterologous production and pharmacological evaluation of CVN is reviewed

Screening of aflatoxin-producing fungi in maize and groundnuts from three regions in Tanzania

This study screened aflatoxin-producing fungi in maize and groundnuts from Dodoma, Singida and Iringa regions in Tanzania, and assessed the level of peoples’ awareness on aflatoxins health effects. One hundred and twenty samples (20 each crop) were collected and inoculated on Sabouraud dextrose agar and one hundred and eleven samples were observed to have fungal growths that were identified to belong to four genera, namely Aspergillus, Rhizopus, Mucor and Dermatophyte with occurrence frequencies of 75, 2.5, 5 and 10%, respectively. Among the four screened genera of fungi, Aspergillus was observed to be the major aflatoxin-producing fungi. Five species of genus Aspergillus, namely A. flavus, A. parasiticus, A. niger, A. fumigatus, and A. terreus were isolated with frequencies of 39.1, 10, 7.5, 15.8 and 2.5%, respectively. Macromorphology and micromorphology of isolated Aspergillus spp were also observed using a light microscope. Furthermore, it was noted that the prevalence of fungi and aflatoxins contamination is more in groundnuts than in maize. In terms of awareness in individuals concerning aflatoxins, only 34% respondents in Dodoma, 29.9% in Singida and 24% in Iringa were aware of aflatoxins. Therefore, the creation of awareness and sensitization on aflatoxins health effects to the people is an important part of intervention ways to forestall and control aflatoxins in Tanzania. Keywords: Aflatoxins, Maize, Groundnuts, Aspergillus spp, A. flavus, A. parasiticus, A. niger, A. fumigatus and A. terreu