Design of an intravaginal composite polymeric system for the reduction and prevention of STI and HIV transmission

This dissertation discusses anti-HIV-1 microbicide research. In particular, it concentrates on microbicide formulation and delivery. Microbicides are anti-HIV-1 agents that when applied in the human vagina or rectum may prevent sexual HIV-1 transmission. Although most of the anti-HIV-1 agents being developed as microbicides are active in vitro, they have proved to be ineffective in vivo. A review of microbicide development over the last decade expounds the view that unsatisfactory microbicide failures may be a result of inefficient delivery systems employed. Thus, necessitating a thorough scientific qualitative and quantitative investigation of important aspects involved in HIV-1 transmission as a prerequisite for microbicide development. In this dissertation it is postulated that intravaginal targeting of HIV-1 increases the chances of microbicide success, wherein vaginal micro-environmental factors including pH would be maintained at HIV-1 prohibitive acidic levels to ward off other sexually transmitted diseases which compromise vaginal epithelial barrier properties. Furthermore, targeting early stages of the HIV-1 infection accompanied by computation and delivery of appropriate microbicide quantities could result in an effective microbicide formulation. In an effort to address microbicide formulation challenges, an intravaginal delivery system able to deliver anti-HIV-1 agents (zidovudine and BP36) over 28 days was formulated. This delivery system is a caplet-shaped composite system comprising zidovudine (AZT) and BP36-loaded pectin-mucin-polyethylene glycol submicrospheres embedded within a poly(D,L-lactide), magnesium stearate, polyvinyl acetate/polyvinylpyrolidone (Kollidon® SR) and poly(acrylic acid) based polymeric caplet matrix. The delivery system was tested in vitro and in vivo in the pig model. X-ray imaging illustrated the delivery system swelling and its matrix contrast fading over time as vaginal fluid permeated the matrix’s core. Plasma, vaginal fluid and tissue drug was detected and quantified using ultra performance liquid chromatography-tandem photodiode array detector. AZT plasma and vaginal fluid concentrations measured on days; 3, 7, 14, 21 and 28 decreased gradually with time. Vaginal tissue AZT concentrations (after 28 days) were higher than plasma AZT concentrations and were in the same range as vaginal fluid AZT concentrations. The herbal extract, BP36, was detected in plasma, vaginal fluid and tissue but was only qualitatively analysed due to its lack of standardization. Histopathological analysis of excised vaginal tissue revealed different scores of abnormalities comprising mild to moderate epithelial proliferation and exocytosis, subepithelial leukocyte influx, perivascular cell cuffing and isolated epithelial erosion, stromal fibrosis and isolated tissue necrosis

Poly(ethylene glycol) enclatherated pectin-mucin submicron matrices for intravaginal anti-HIV-1 drug delivery

This paper explores the potential of polyethylene glycol enclatherated pectin-mucin (PEGencl- PEC:MUC) submicron matrices (SMMs) as an intravaginal drug delivery system capable of delivering an anti-HIV-1 agent (zidovudine; AZT) over a prolonged duration. A three factor and three level (33) Box-Behnken statistical design was employed to optimize the SMMs. Optimized PEG-encl-PEC:MUC SMMs prepared as a stable W/O emulsion (determined by the degree of reversible colloidal phenomena) were spherical with a mean particle size of 270.6±5.533nm and mean zeta potential of -34.4±0.539mV. The microencapsulation of AZT and the hydrogen bonding mediated shielding of AZT by SMMs was confirmed by Fourier Transform Infrared (FTIR) analysis. The thermochemical (differential scanning calorimetry and thermogravimetric analysis) data proposed that Ca2+- based macromolecular ionic crosslinking as well as the intermolecular interactions may be responsible for the thermal stability of the delivery system. The partially amorphous nature of drug-loaded SMMs, as confirmed by X-ray diffraction patterns, further strengthened the matricization of AZT into the pectin-mucin matrix. In vitro drug release studies from the SMMs showed approximately 91% zidovudine release in simulated vaginal fluid (SVF) and 94% in phosphate buffered saline (PBS) in 24 hours. The mean dissolution time (MDT) of zidovudine from the SMMs was 5.974 hours. The attainment of required dimensional structure and drug release profiles from SMMs highlights the potential of their inclusion into a secondary carrier system for extended and controlled intravaginal stay.National Research Foundation (NRF) of South Africa.http://www.elsevier.com/locate/ijpharm2017-04-30hb2016Chemistr

Critical reflection on knowledge and narratives of conservation agriculture

In the context of contemporary concerns about climate change and food security, Conservation Agriculture (CA) has emerged as a well-supported and central component of the agricultural sector development strategy across sub-Saharan Africa, including in Zambia, which is the focus of this paper. A variety of narratives about the benefits of CA over conventional agricultural systems underpin endeavours towards ‘scaling up’ CA and increasing rates of adoption amongst smallholder farmers nationwide. However, there is a knowledge politics underlying the translation of a weak evidence base around CA into persuasive narratives and financial and political support. In this paper, we trace the evolution of five narratives around CA in Zambia in relation to changing political agendas and the involvement of new public and private sector actors, and review the development of evidence bases and knowledge that support and challenge each of these narratives. We discuss the potential to open up space within this knowledge politics to alternative narratives and the contestation of the pervasive CA scaling up agenda. Critical reflection is essential to ensure that national and local evidence is more effectively used to guide national climate and agricultural policy developments and international donor initiatives

Genetic trends in CIMMYT’s tropical maize breeding pipelines

Fostering a culture of continuous improvement through regular monitoring of genetic trends in breeding pipelines is essential to improve efficiency and increase accountability. This is the first global study to estimate genetic trends across the International Maize and Wheat Improvement Center (CIMMYT) tropical maize breeding pipelines in eastern and southern Africa (ESA), South Asia, and Latin America over the past decade. Data from a total of 4152 advanced breeding trials and 34,813 entries, conducted at 1331 locations in 28 countries globally, were used for this study. Genetic trends for grain yield reached up to 138 kg ha−1 yr−1 in ESA, 118 kg ha−1 yr−1 South Asia and 143 kg ha−1 yr−1 in Latin America. Genetic trend was, in part, related to the extent of deployment of new breeding tools in each pipeline, strength of an extensive phenotyping network, and funding stability. Over the past decade, CIMMYT’s breeding pipelines have significantly evolved, incorporating new tools/technologies to increase selection accuracy and intensity, while reducing cycle time. The first pipeline, Eastern Africa Product Profile 1a (EA-PP1a), to implement marker-assisted forward-breeding for resistance to key diseases, coupled with rapid-cycle genomic selection for drought, recorded a genetic trend of 2.46% per year highlighting the potential for deploying new tools/technologies to increase genetic gain

Submicron matrices embedded in a polymeric caplet for extended intravaginal delivery of Zidovudine

In this study, an intravaginal delivery system able to deliver an anti-HIV-1 agent for the purpose of potentially reducing HIV-1 transmission acting over an extended duration was successfully formulated. This delivery system was a composite polymeric caplet comprising zidovudine-loaded polyethylene glycol enclatherated pectin-mucin submicron matrices embedded within a poly (D,L-lactide), magnesium stearate, Kollidon® SR, and Carbopol® 974P NF-based polymeric caplet matrix. A three-factor and three-level Box-Behnken statistical design was utilized to optimize the polymeric caplet. The optimized directly compressed composite polymeric caplet hardness was 22.1 ± 0.3 N and the matrix resilience was 62.4 ± 0.6%. The swelling- and diffusion-controlled fractional zidovudine (AZT) release from the optimized caplet was 0.74 ± 0.01 in simulated vaginal fluid (SVF), which increased to 0.81 ± 0.21 in phosphate-buffered saline (PBS) simulating seminal fluid, over 30 days. Caplet matrix swelling was directly related to the percentage Carbopol 974P NF composition. An intravaginal system for AZT delivery was tested in the pig model over 28 days. X-ray analysis depicted delivery system swelling with matrix contrast fading over time as vaginal fluid permeated the matrix core. Plasma, vaginal fluid swab eluates, and tissue AZT concentrations were measured by gradient ultra-performance liquid chromatography (UPLC)-tandem photodiode array detection. Vaginal tissue and vaginal fluid swab eluate AZT concentrations remained above effective levels over 28 days and were higher than plasma AZT concentrations, availing a system with reduced systemic toxicity and more effective inhibition of viral replication at the site of entry.This study was derived from the Master’s dissertation of first author, Felix Mashingaidze, submitted 24 March 2014.The Council for Scientific and Industrial Research, South Africa (CSIR SA), the South African National Research Foundation (NRF) and the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.https://link.springer.com/journal/122482018-11-04hj2017Chemistr

Poly(ethylene glycol) enclatherated pectin-mucin submicron matrices for intravaginal anti-HIV-1 drug delivery

This paper explores the potential of polyethylene glycol enclatherated pectin-mucin (PEGencl- PEC:MUC) submicron matrices (SMMs) as an intravaginal drug delivery system capable of delivering an anti-HIV-1 agent (zidovudine; AZT) over a prolonged duration. A three factor and three level (33) Box-Behnken statistical design was employed to optimize the SMMs. Optimized PEG-encl-PEC:MUC SMMs prepared as a stable W/O emulsion (determined by the degree of reversible colloidal phenomena) were spherical with a mean particle size of 270.6±5.533nm and mean zeta potential of -34.4±0.539mV. The microencapsulation of AZT and the hydrogen bonding mediated shielding of AZT by SMMs was confirmed by Fourier Transform Infrared (FTIR) analysis. The thermochemical (differential scanning calorimetry and thermogravimetric analysis) data proposed that Ca2+- based macromolecular ionic crosslinking as well as the intermolecular interactions may be responsible for the thermal stability of the delivery system. The partially amorphous nature of drug-loaded SMMs, as confirmed by X-ray diffraction patterns, further strengthened the matricization of AZT into the pectin-mucin matrix. In vitro drug release studies from the SMMs showed approximately 91% zidovudine release in simulated vaginal fluid (SVF) and 94% in phosphate buffered saline (PBS) in 24 hours. The mean dissolution time (MDT) of zidovudine from the SMMs was 5.974 hours. The attainment of required dimensional structure and drug release profiles from SMMs highlights the potential of their inclusion into a secondary carrier system for extended and controlled intravaginal stay.National Research Foundation (NRF) of South Africa.http://www.elsevier.com/locate/ijpharm2017-04-30hb2016Chemistr

Not Available

Not AvailableFostering a culture of continuous improvement through regular monitoring of genetic trends in breeding pipelines is essential to improve efficiency and increase accountability. This is the first global study to estimate genetic trends across the International Maize and Wheat Improvement Center (CIMMYT) tropical maize breeding pipelines in eastern and southern Africa (ESA), South Asia, and Latin America over the past decade. Data from a total of 4152 advanced breeding trials and 34,813 entries, conducted at 1331 locations in 28 countries globally, were used for this study. Genetic trends for grain yield reached up to 138 kg ha− 1 yr− 1 in ESA, 118 kg ha− 1 yr− 1 South Asia and 143 kg ha− 1 yr− 1 in Latin America. Genetic trend was, in part, related to the extent of deployment of new breeding tools in each pipeline, strength of an extensive phenotyping network, and funding stability. Over the past decade, CIMMYT’s breeding pipelines have significantly evolved, incorporating new tools/technologies to increase selection accuracy and intensity, while reducing cycle time. The first pipeline, Eastern Africa Product Profile 1a (EA-PP1a), to implement marker-assisted forward-breeding for resistance to key diseases, coupled with rapid-cycle genomic selection for drought, recorded a genetic trend of 2.46% per year highlighting the potential for deploying new tools/technologies to increase genetic gainCIMMYT, Hyderabad and ICA