HULDA SWAI PhD
Research Group Leader- Encapsulation & Delivery
Polymers & Composites, Council for Scientific and Industrial Research
PO Box 395 Pretoria 0001 South Africa
Tel: +27 12 841 2366, Fax: +27 12 841 3553, Email: hswai@csir.co.za
THE CSIR NANOMEDICINE PLATFORM
FOR INFECTIOUS DISEASES OF
POVERTY
1. BACKGROUND
Infectious Diseases of Poverty (IDP) are the major
cause and consequence of considerable poverty in
developing countries, particularly those in Sub-Saharan
Africa. The annual global death toll of HIV/Aids, malaria
and tuberculosis (TB) approaches 6 million people.
Fighting these diseases remains one of the most
effective ways to alleviate poverty and promote
economic progress in these countries.
Although effective therapeutic regimens against these
diseases are available, treatment failure due to poor
adherence (which in turn leads to the emergence of drug
resistant strains) remains a challenge. Other shortfalls of
current therapies include high dose and dose frequency
due to poor bioavailability, hence the long treatment
durations and associated negative side effects. These in
turn lead to poorer treatment outcomes and increased
cost of treatment. Accordingly, the drawbacks of
conventional therapy necessitate the development of a
delivery or carrier system which can release the drug in
a slow and steady manner over a period of time to the
affected parts of the body.
2. NANOMEDICINE: A NOVEL APPROACH
TOWARDS IMPROVING IDP THERAPIES
Nanotechnology for drug delivery offers a suitable
means of delivering small molecular weight drugs as
well as macromolecules such as proteins, peptides or
genes to specific tissues and intracellular compartments.
Nanoparticles are submicron-sized (less than 1 micron)
polymeric colloidal particles with a therapeutic agent
encapsulated within their polymeric matrix, or adsorbed
or conjugated onto the surface. The release of the active
agent may be constant over a long period; it may be
cyclical or triggered by the environment or another
external event. These particles in the submicron range
possess very high surface to volume ratios, thus
allowing for an intimate interaction between the surface
of the particles and the mucus of various tissues.
Additionally, carriers in the particulate form reportedly
diffuse further into the mucus layer, enabling them to
reach the cells. The major advantage of nanoparticulate
drug delivery systems is that the release of the active
agent can be controlled and sustained. Thus, the
release may be cyclical or triggered by the environment
or yet, by another external event.
We propose the use of nanomedicine to address the
current shortfalls of IDP therapies. With the use of
nanotechnology, we envisage that our polymeric nanosystems will enable entry and retention of the drugs in
the cells. Nanoparticles also facilitate the subcellular
distribution and activity of the drugs in the infected cells,
thus addressing the major shortfalls of failed HIV/Aids,
malaria and TB therapies. In addition, these carrier
systems will also reduce unwanted systemic side effects
associated with conventional free drugs.
This new approach will increase the availability of the
drug at the target area, therefore enabling reduction of
the currently high dose and dose frequency, treatment
time and toxicity/unpleasant side effects associated with
current IDP therapies. We envisage that
nanotechnology-based drug delivery will improve patient
compliance to treatment, treat drug resistant cases more
effectively and reduce the infection rates. An additional
advantage is that our approach is generic, in that any
drug (i.e. anti-malarial, anti-retroviral, anti-cancer, antiTB drugs, etc.) can be encapsulated and delivered in a
slow-controlled release mode.
Using TB as a model disease and case study, we are
building a platform in South Africa where we will
encapsulate both current and novel therapeutic drugs for
the above-mentioned disease as well as those of other
neglected diseases that affect South Africa and other
developing countries in the world.
3. TB – A PROBLEM WITH PERSISTENCE
Every 20 seconds, a person dies from TB. It is the
leading cause of death in South Africa, with 13% of all
deaths resulting from the disease. There were 460,000
new cases of TB in 2007. South Africa now ranks 5th on
the list of 22 TB High Burden Countries.
The prevalence of TB is exacerbated due to the coinfection with HIV/Aids. The economic implications of TB
are often overlooked, particularly in developing countries
like South Africa. More than two-thirds of TB patients are
in their economically productive years of life. TB
undermines economies in a variety of ways. As
breadwinners, youthful TB sufferers are unable to
provide for their typically large families. These are young
to middle-aged men and women in whom society has
invested heavily; hence, long periods of dilapidation and
eventual death rob the nation of hard-earned skills for
development. Some of the causal economic and social
1
HULDA SWAI PhD
Research Group Leader- Encapsulation & Delivery
Polymers & Composites, Council for Scientific and Industrial Research
PO Box 395 Pretoria 0001 South Africa
Tel: +27 12 841 2366, Fax: +27 12 841 3553, Email: hswai@csir.co.za
repercussions appear long after a TB patient has died,
leaving widows or widowers and orphans with a poor
start in life.
The fixed dose combination has proven to be effective in
curing TB when taken according to prescription.
However, patient non-compliance to treatment, due to
some of the afore-mentioned reasons, has led to the
escalation of TB cases and the emergence of multidrug
resistant (MDR) total drug resistant (TDR) and extreme
drug resistant (XDR) to TB, particularly in Africa, leading
to treatment failure. Furthermore, clinical management
of these diseases is limited because of toxic side effects
of the drugs, degradation of drugs before reaching their
target site, and low permeability.
4. THE CSIR TB NANO DRUG DELIVERY
PROJECT
4.1
Background
The CSIR (Council for Scientific and Industrial
Research) is a leading scientific and technology
research organisation, implementing research projects
throughout Africa and making a difference in people’s
lives.
Our group (Encapsulation & Delivery Research Group)
is developing a nanotechnology-based targeted drug
delivery system (DDS) that will improve the current
inadequate therapeutic management of TB. We
envisage that our DDS will target infected cells, and
enable easier entry; slow release and retention of the
antibiotics in the cells for longer, hence reducing the
current dose frequency from daily to once-a-week intake
of antibiotics, and lessen the total standard treatment
time from six to two months.
4.2
Nano-encapsulation or Anti-TB Drugs
We have successfully nano-encapsulated four first line
anti-TB drugs: Isoniazid (INH), Rifampicin (RIF),
Ethambutol (ETB) and Pyrazinamide (PZA) with an
encapsulation efficiency varying from 50-65% in particle
of 250-400nm, using a novel multiple emulsion spraydrying technique. The polymer used is Poly(lactide-coglycolide), PLGA. We have filed a patent application on
the method of preparing the nanoparticles, and have
received an International Search Report from reviewers
confirming its novelty.
4.3
In vitro assays
We observed through in vitro release assays performed
in phosphate buffer solution (PBS) at various pH ranges,
that the drugs were released in a slow manner over a
period of several days. Furthermore, we have performed
intracellular drug delivery studies in CaCo-2 cells,
human colonic adenocarcinoma cell line and U937 cells,
and a human leukemic monocyte lymphoma cell line.
The results indicate that the particles are taken up by
the cells within 30 minutes and in the case of the U937
cells, these particles are released from the phagosomes
into the cytoplasm. Thus based on these results,
intracellular delivery of the drugs will be feasible. We
have also illustrated that the bacterial growth index in
THP-1 cells treated with encapsulated RIF was reduced
significantly when compared to that of cells treated with
free Rifampicin. Extra cellular bacteria were also killed
by the encapsulated drug over a period of time.
4.4
In vivo assays
We
administered
fluorescently-labelled
PLGA
nanoparticles to Balb/C mice, and performed
fluorescence detection via FACS. The particles were
detected in the macrophages of the peritoneum cell
exudates and all other tissues analysed. These results
indicate that the nanoparticles can go to all tissues of
the body, and even cross the blood brain barrier. We
also conducted histopathology assays on all major
tissues, that is, spleen, lungs, kidney, liver, spleen, heart
and the brain, and observed no lesions, implying that the
nanoparticles are not toxic.
We observed through assays in mice that the drugs
were released over a period of six days and the
minimum inhibitory concentration MIC for RIF and INH
was maintained over this period. An efficacy study was
performed over four weeks, in which equal doses of the
free drugs were administered to HR37V TB-challenged
mice once every day, or the encapsulated drugs once
every seven days. The encapsulated drugs showed
comparative efficacy to the free drugs, against the
TB bacterium, and the cfu counts obtained from of
the treated mice were significantly different to those
of the untreated mice (control). These are important
results because they confirm the feasibility of slow
release, and reduced dose frequency. Further
optimisation of the formulation and more in vivo assays
are underway.
4.5
Targeted drug delivery
4.5.1 Targeting with aptamers
2
HULDA SWAI PhD
Research Group Leader- Encapsulation & Delivery
Polymers & Composites, Council for Scientific and Industrial Research
PO Box 395 Pretoria 0001 South Africa
Tel: +27 12 841 2366, Fax: +27 12 841 3553, Email: hswai@csir.co.za
Our team has embarked on targeted drug delivery, a
project in which we aim to functionalise slow-release
polymeric nanoparticles to target TB drugs to infected
macrophage cells. These cells serve as a reservoir for
Mycobacterium Tuberculosis (M tb), where the bacteria
persist, shielded from the anti-bactericidal effects of the
administered drugs. Since TB primarily targets the
alveolar macrophages, macrophages are a key cell type
to which our drug delivery vehicles will target. Targeting
has been achieved via attaching nucleic acid aptamers
specific for the target protein receptor onto the surface
of aptamers functionalised Poly(lactide-co-glycolide)
nanoparticles. The specific objective of the project is to
develop an active targeted drug delivery system that will
enable localised delivery of the anti-TB drugs to the
infected macrophages via aptamers targeting and also
slowly release the drugs over a number of days as a
function of the nanoparticles delivery. For this specific
phase, our team has focused on selection of aptamers
against the target protein receptor, conjugating the
aptamers to the particles. We will illustrate in cell culture
that there is specific localisation of the particles on cells
that over express the mannose receptor. Pre-clinical
studies will then follow. This aspect of the work is funded
by the Bill & Melinda Gates Foundation, under the
Grand Challenges Programme.
4.5.2 Targeting with mycolic acids
This aspect of our work exploits the unique lipid cell wall
composition of M. tuberculosis and other pathogenic
mycobacteria. The targeting compound could also be
part of the polymer for encapsulating.
4.6
The use of natural polymers for
encapsulating anti-TB drugs
The purpose of the project is to investigate the use of
natural polymers: chitosan and alginate, as potential
nanocarriers as alternatives to the current antituberculosis nano-drug delivery system using PLGA.
Our early studies with natural polymers showed that it
was possible to achieve alginate-chitosan and chitosantripolyphosphate particles on the submicron scale. The
current work focuses on the use of hydrophobically
modified chitosan (HM CS) for drug delivery to address
these challenges of low drug loading and low recovery
of nanoparticles. Chitosan is modified via an n-acylation
process. These N-acylated chitosans offer several
advantages such as the hydrophobicity they introduce to
the matrix. This enhances the network stabilisation
through the hydrophobic interactions that ultimately
leads to the increase of drug release times.
A preliminary study of the hydrophobically modified
chitosan (HM CS) and tripolyphosphate (TPP) as
potential nano-carriers has been investigated. The study
showed promise towards the development of a natural
polymer-based drug delivery system. An optimisation
study of the process of modification to the chitosan is
currently underway.
5. OTHER ACTIVITIES AT THE CSIR
NANOMEDICINE PLATFORM FOR IDP
5.1
Nanomedicine for HIV/Aids
5.1.1 Background
Nowhere in the world is the HIV/Aids epidemic more
prevalent than in sub-Saharan Africa. An estimated 5.2
million people were living with HIV and Aids in South
Africa in 2008, more than in any other country. National
prevalence is around 11%, with some age groups being
particularly affected. Almost one-in-four people aged 15
to 49 years, one-in-three women aged 25 to 29, and
over a quarter of men aged 30 to 34, are living with HIV.
In the same year, over 250,000 South Africans died of
Aids. Currently, it is estimated that in South Africa, there
are 600 000 orphaned children as a result of Aids. A
survey done in 2004 reported that South African citizens
spend more time at funerals than at weddings, hair
salons or grocery shops!
The impact of the HIV/Aids epidemic is proving to be
most catastrophic at household level. Increasing levels
of HIV/Aids morbidity and mortality pose a serious threat
to food security and nutrition in households. Families
lose income earners; household expenditure is
redirected to cover non-food items such as medical
costs and funerals; children are taken out of school for
lack of fees or to care for sick relatives; workers have to
take time-off to provide terminal care; resources may
have to be shared with more dependents; and
productive assets are sold off.
5.1.2 Encapsulation of Anti-Retrovirals (ARVs)
The main goal of this project is to develop a nanoparticle
ARV drug delivery system that will protect the ARVs
from degradation, reduce toxicity, increase bioavailability
and allow sustained drug release. FDA approved
polymers namely, PLGA and poly(caprolactone) (PCL)
3
HULDA SWAI PhD
Research Group Leader- Encapsulation & Delivery
Polymers & Composites, Council for Scientific and Industrial Research
PO Box 395 Pretoria 0001 South Africa
Tel: +27 12 841 2366, Fax: +27 12 841 3553, Email: hswai@csir.co.za
will be investigated because nanoparticles loaded with
ARVs based on the available literature search using
these polymers is limited or lacking. The following ARVs
namely, lamivudine, stavudine, efavirenz and nevirapine
are currently used as first line drugs in South Africa will
be used in the project. Parameters such as toxicity, drug
release, efficacy; short and long term will be evaluated.
We hypothesise that using this system; drug release can
be prolonged, allowing for a single administration of
drugs to last for several days or weeks instead of the
current daily administration. In addition, these will
therefore minimise the side effects and the dose levels,
thus in turn improve patient compliance and contribute
towards one of the aims of national strategic plan for
HIV/AIDS 2007-2011 of South Africa, which is to expand
treatment to 80% of HIV-infected individuals.
antimalarials currently available. Quinine is generally
effective against CQ-resistant falciparum malaria, but its
use is limited by its narrow therapeutic index and
cardiotoxicity effects.
5.2
We plan to nano-encapsulate current drugs used in
malaria prophylaxis/therapy (CQ, artemisin, artesunate)
by applying one of our encapsulation techniques
(multiple emulsion spray/freeze drying or SCF). The
anti-malarial nanoparticles can also be functionalised for
targeted delivery to the cells. After successful
encapsulation, the actives will be study investigated and
evaluated in vitro and in vivo to determine their
biodistribution, efficacy, toxicity, and so forth and further
evaluated
in
other
pharmacokinetic
and
pharmacodynamics studies.
Nanomedicine for Malaria
5.2.1 Background
Malaria is one of the planet's deadliest diseases and one
of the leading causes of sickness and death in the
developing world. About 3.3 billion people – half of the
world's population – are at risk of malaria. Malaria is
especially a serious problem in sub-Saharan Africa
where at least 90% of malaria deaths occur each year,
and primarily among pregnant women and young
children. An African child (usually from 1 to 4 years of
age) has on average between 1.6 and 5.4 episodes of
malaria fever each year, and one in every five (20%)
childhood deaths is due to the effects of the disease.
According to the World Health Organisation (WHO)
reports, a child dies from malaria every 30 seconds,
hence about 3 000 children who are under the age of
five die each day, summing up to over 1 million deaths
per year.
Currently no effective vaccine against malaria is
available but the effort to find one is ongoing.
Chloroquine (CQ) has been the mainstay of malaria
treatment for many decades, but development of drug
resistance by the parasite has led to therapeutic failure.
With the deployment of artemisinin-based combination
therapy (ACT) in 2005/2006 as first-line treatment in
several endemic countries in Africa, the malaria cases
and deaths have been reported to be on the decline.
However, the reported parasites that have low sensitivity
to ACTs in South East Asia threaten this good news. In
the past, parasites that are resistant to CQ and antifolates emerged from this region and spread to the east
coast of Africa and from there to the rest of Africa. If
resistance emerges against ACTs, then, the result will
be catastrophic considering the limited number of
5.2.1 Encapsulation of Anti-Malarials
To overcome the challenge posed by multi-drug
resistance, new strategies for intracellular antimalarial
delivery based on nanotechnology are urgently needed.
We propose the use of nanomedicine to address the
current shortfalls of malaria therapies. Through this
approach, we will be able to increase the availability of
the drug at the target area, therefore enabling reduction
of the currently high dose and dose frequency, treatment
time and less toxicity.
Based on our successes and experiences obtained
through the CSIR TB nanodrug delivery project, we
envisage that this part of the project will go at a faster
pace. We also have a good network of collaborators
whose expertise and infrastructure are available to us to
facilitate our progress.
5.3
Nanomedicine
infectious diseases
for
other
IDP
and
Part of the vision of the CSIR Nanomedicine platform for
IDP is to nano-encapsulate other drugs which suffer the
same treatment shortfalls and outcomes as TB, HIV and
Malaria. We also envisage the encapsulation of
scientifically-validated herbal medicines or lead
traditional active compounds. This work will be done in
close collaboration with bioprospecting research groups
and indigenous knowledge systems.
6. NETWORKS AND COLLABORATIONS
6.1
Background
4
HULDA SWAI PhD
Research Group Leader- Encapsulation & Delivery
Polymers & Composites, Council for Scientific and Industrial Research
PO Box 395 Pretoria 0001 South Africa
Tel: +27 12 841 2366, Fax: +27 12 841 3553, Email: hswai@csir.co.za
Our platform operates in a core consortium which
comprises CSIR Materials Science & Manufacturing
(MSM), CSIR-Biosciences, University of Pretoria and
University of Stellenbosch; and collaborates extensively
with several prestigious academic and research
institutions, as well as private companies, nationally,
regionally and internationally.
Most of the consortium and collaborative agreements
allow for the sharing equipment/facilities, skills/expertise,
laboratory exchange programmes, sabbaticals, joint
projects and project proposals, co-supervision of
students, organising joint workshops and so forth.
Thus far, 11 lab exchange programmes, 4 research
visits, 2 sabbaticals have been completed. All the
graduate students in the programme are co-supervised
with collaborators based at the Universities of Pretoria
and Stellenbosch.
Some of the international training programs have been
completed at the following institutions:







University of London, UK
Cardiff University, UK
University of Nottingham , UK
African Institute of Biomedical Science and
Technology in Zimbabwe
Swiss Institute of Technology – Ecole
Polytechnique federal de Lausanne in Switzerland
Auburn University – Alabama, USA
Colorado State University
Dr Khati is a molecular pathologist specialising in HIV
entry and its interaction with host cells (macrophages
and T cells). He leads the aptamer technology group
which investigates biomedical systems and the
molecular basis of diseases to provide cutting-edge
solutions to major public health problems such as
HIV/Aids and TB. The Biosciences Unit has extensively
equipped research laboratories in the field of
Biotechnology. Our work on targeting with aptamers at
CSIR Biosciences is in collaboration with his group.
Dr D Mancama- specialises in functional genomics and
leads the systems biology area, a newly-established
research group at CSIR Biosciences that incorporates
several leading technology platforms including
transcriptomics, proteomics, metabolomics and
bioinformatics. He also integrates synthetic and
medicinal chemistry capabilities in the CSIR's discovery
chemistry research group to guide the rational design
and synthesis of improved anti-malarial leads based on
synthetic and naturally-derived chemical scaffolds. He is
also working to expedite the development of plantderived pharmaceuticals with the current focus being on
malaria, and adds value to the development of novel
plant-based expression systems for the production of
therapeutic proteins and peptides, by elucidating key
molecular components and interactions in these
systems that can subsequently be modified to undertake
the process more efficiently. We have also submitted
another proposal to Grand Challenge in collaboration
with Dr. Mancama on malaria, and will in future apply
nanomedicine to the traditional medicinal extracts.
6.2.2 University of Pretoria (through Prof Jan Verschoor)
6.2
National Collaborations
Dr Hulda Swai, who leads the consortium, is a Senior
Principal Researcher at the CSIR and is the Research
Group Leader of the Encapsulation and Delivery (E&D)
group within the CSIR-MSM business unit. She has
been working in polymeric drug delivery systems for the
past 10 years. Developing a nano-encapsulation
delivery system for anti-TB drugs is her concept idea.
With support from the E&D team, consortium and
collaborators listed below, she has since grown the
concept to a platform. She oversees the running of all
the projects within the platform.
6.2.1 CSIR Biosciences (through Dr Makobetsa Khati &
Dr Dalu Mancama)
Prof Verschoor, initiated the tuberculosis research
programme in 1994 at the University of Pretoria where
he is the principal investigator. He is the Head of
Department of Biochemistry, which has a wellestablished research laboratory with a good basic
research infrastructure and access to equipment and
expertise within the greater university community and
other local research institutions. We collaborate with
Prof Verschoor on targeting with mycolic acids. This
project is being accomplished by a PhD student, jointly
supervised by Prof Verschoor and Dr Boitumelo Semete
(CSIR-MSM).
6.2.3 The University of Stellenbosch (through Prof Peter
Donald)
Prof Donald has done extensive work on TB drugs
pharmacokinetics, bactericidal activity of TB and is the
leading authority in TB drug and related clinical trials in
5
HULDA SWAI PhD
Research Group Leader- Encapsulation & Delivery
Polymers & Composites, Council for Scientific and Industrial Research
PO Box 395 Pretoria 0001 South Africa
Tel: +27 12 841 2366, Fax: +27 12 841 3553, Email: hswai@csir.co.za
the country. He contributes his expertise towards
planning our experiments in that respect.
6.2.4 Medical Research Council (MRC)
Dr Kobus Venter is an accredited researcher on TBchallenged mice. We collaborate on the pharmacokinetic
tissue distribution, as well as toxicity studies of the
nanoparticle encapsulated TB drugs in mice.
Dr Jurgen Seier assists in preclinical trials in non-human
primates, by analysing how non-human primates react
to nanoparticles, as well as to determine distribution of
the particles the tissues of the animals.
Prof Paul David van Helden is the Director, MRC Centre
for Molecular and Cellular Biology, and Chair of
Department Medical Biochemistry at the University of
Stellenbosch. He is well-equipped and qualified to
coordinate clinical human trials.
investigate the relationship between M tuberculosis
infection and the host immune response with emphasis
on Tumour Necrosis Factors and Pathogen Recognition
Receptors. He contributes to or projects through the
preclinical trial in vivo assays in TB challenged mice.
6.2.7 University of Johannesburg (Prof Rui Krause)
Prof Krause is the Head of Nanomaterials Science
Focus. His research interests include the development
and application of shaped nanomaterials for various
biomaterials applications, including drug delivery and
targeting. Through co-supervision of an MSc student, we
are looking at developing and optimising various
polymeric drug encapsulation techniques that can be
applied to the delivery of IDP therapies.
6.3
International Collaborations
6.3.1 University of London
6.2.5 North-West University – Potchefstroom campus
(through Dr Anne Grobler
Dr Grobler is a Senior Scientist in the School of
Pharmacy, whose research interest revolves around
drug delivery, infectious diseases and bio-agriculture.
The school has a state-of-the-art confocal fluorescent
microscope which will be used to elucidate the mode of
transport of the nanoparticles into the tissues/cells. We
collaborate on the drug analysis assays that will be
performed from tissue homogenates and plasma
samples from preclinical trials in mice. This work is part
of a student’s PhD, jointly supervised by Dr Grobler and
Dr Semete (CSIR).
6.2.6 University of Cape Town (Prof Peter Smith and
Prof Muazzam Jacobs)
Prof Smith is a Principal Specialist Scientist in the
Department of Pharmacology at the University of Cape
Town (UCT), where he runs the analytical laboratory.
This Pharmacology laboratory is one of only three
laboratories worldwide that is recognised by the WHO
as reference centres for TB drug monitoring. He has
extensive experience in drug assay development and in
the pharmacokinetics of anti-TB drugs, and lends this
expertise in our collaboration on Pharmacokinetic
studies of nano-encapsulated anti-TB drugs.
Prof Jacobs is a Specialist Scientist at the Department
of Immunology at UCT. His current research focus is to
Prof Oya Alpar is an Emeritus Professor for drug
delivery research. Her main research focus is on the
formulation and development of active macromolecular
biological entities. Her group specialises in pulmonary
delivery of nano-encapsulated drugs, as well as nanoencapsulation of traditional actives against TB. Three
lab exchange visits have taken place through this
collaboration, during which researchers acquired skills in
nano-encapsulation, BAL technology and assays.
Prof Peter Taylor's major research interest involves
novel approaches to the treatment of infectious disease;
he is particularly interested in opportunities to develop
therapeutics that suppress or abrogate the emergence
of drug resistant variants by modification of the bacterial
phenotype. Our collaboration is on lead anti-TB
compounds, and possibly joint submission of proposals
and lab exchange visits.
6.3.2 University of Nottingham – UK (Prof Alexander
Cameron)
Prof Cameron – Head of Division of Drug Delivery and
Tissue Engineering – focuses on the synthesis of
polymers for biomedical applications, especially drug
and gene delivery. He has expertise in conjugating
molecules onto the surface of polymers for various
modes of delivery. We collaborate through lab exchange
visits; to share skills and techniques for synthesising
polymer-drug conjugates which can be used to target
6
HULDA SWAI PhD
Research Group Leader- Encapsulation & Delivery
Polymers & Composites, Council for Scientific and Industrial Research
PO Box 395 Pretoria 0001 South Africa
Tel: +27 12 841 2366, Fax: +27 12 841 3553, Email: hswai@csir.co.za
and deliver anti-TB drugs to the macrophages. Three
such visits have been completed.
6.3.3 Cardiff University – UK
Professor Ruth Duncan, head of the Pharmacy School’s
Centre for Polymer Therapeutics, has applied the
principles of nanotechnology – engineering at a
molecular level – to the design of a new class of
therapeutics. Her team has led the design and clinical
development of polymer-based therapeutics and were
responsible for the transfer of this first polymer-based
cancer treatment into clinical trials. Our collaboration is
on intracellular drug delivery research.
Dr Arwyn Jones is a cell biologist with major interest in
endocytosis and cellular delivery of therapeutic
macromolecules. We collaborate through lab exchange
visits on the encapsulation of mycolic acids into solid
matrices like PLGA nanoparticles.
6.3.4 Postgraduate Institute of Medical Education
(PGIMER) – India (Prof Gopal Khuller)
Prof Khuller is the Head of the Department of BioChemistry at the Postgraduate Institute of Medical
Education and Research Chandigarh India. He has been
actively engaged in TB research for more than 30 years.
His interests include antigen-based vaccine
development against TB, diagnostic test and polymerbased drug delivery systems. We collaborate through
lab exchange visits on nanoecapsulation of anti-Tb
drugs, drug analytical techniques and in vitro release
studies.
6.3.5 Swiss Institute of Technology – Ecole
Polytechnique federal de Lausanne (EPFL) (Prof Jeffrey
Alan Hubbell)
Prof Hubbell’s research is directed toward tissue
engineering, cell-based therapies, drug delivery, and
medical devices. He is involved in the development of
nanocapsules for sustainable delivery, including the
synthesis of polymersomes, another class of polymeric
drug delivery systems. Through lab exchange, we
collaborate on the use of amphiphilic block copolymers
of PEG and polypropylene sulfate (PPS), to form
micelles with a hydrophobic core and rubbery-core
nanoparticles of PPS, which are referred to as pluronics,
to form solid particles within a nano-size range (30-100
nm).
6.3.6 Colorado State University (Prof Anne Lenearts)
Prof Lanaerts – a molecular biologist seeks to establish
and validate new in vitro and in vivo models to improve
evaluation of novel TB drugs against active and latent
TB. She is at the epicentre of the search for new TB
drugs, in part through a programme supported by the
National Institutes of Health (NIH) and the National
Institute for Allergies and Infectious Diseases. She has
developed a number of laboratory tests and systems to
improve and accelerate the testing of TB drugs. We
collaborate on preclinical trial assays to evaluate our
nano-encapsulated anti-TB drugs in non-human
primates by NIH and NIAID standards.
6.3.6
African Institute of Biomedical Science and
Technology (AiBST) – Zimbabwe (through Dr Collen
Masimirembwa)
Dr Masimirembwa is a Biochemical Pharmacologist. He
is the founding President and Chief Scientific Officer of
the AiBST. His research interests are Industrial Drug
Metabolism and Pharmacokinetics (DMPK) and
Pharmacogenetics of Drug Metabolism, as well as
molecular diagnostics in the treatment of infectious
disease. Our collaboration with AiBST is towards the
sciences and technologies of drug discovery and
development in Africa.
6.3.7 Universidad Federal Grande Rio du Sul – Brazil
(through Prof Adriana Pohlman)
Prof Pohlman’s research interests include the synthesis,
and characterisation therapeutic compounds. We
collaborate on Microdialysis, Good Manufacturing
Practice (GMP) production and formulation of
nanoparticles.
6.3.7 Auburn University – Alabama, USA (through Prof
Gupta)
Prof Gupta is a Chemical Engineer with extensive
research experience in nanomedicine, energy and fuels.
Through lab exchange and joint proposal submissions,
our collaboration focuses on the Supercritical antisolvent technique (SAS) – a "green" technology that
allows production of polymeric nanoparticles with less
organic solvent.
6.4
Other Collaborators
7
HULDA SWAI PhD
Research Group Leader- Encapsulation & Delivery
Polymers & Composites, Council for Scientific and Industrial Research
PO Box 395 Pretoria 0001 South Africa
Tel: +27 12 841 2366, Fax: +27 12 841 3553, Email: hswai@csir.co.za
Regional collaboration is important towards establishing
such a platform as it would be most beneficial to Africa.
We have collaborations in the pipeline with the following
institutions:
6.4.1 University of Nairobi – Kenya
Prof Francis Mulaa is a Biochemist with research
interest in malaria molecular biology. We will collaborate
on targeted delivery of malaria drugs.
Dr Onyari is a Chemist with research interests in
polymers. Our collaboration is towards natural and
synthetic polymers for encapsulation.
6.4.2 University of Mauritius (Prof Dhanjay Jhurry)
Prof Jhurry is an established polymer chemist in the
area of polymeric drug delivery. Together, we seek ways
to use natural and synthetic polymers for drug
encapsulation.
6.4.3 National Institute for Medical Research (NIMR) –
Tanzania (through Dr Hamisi Malebo)
Dr Malebo is a Senior Research Scientist and heads the
Department of Traditional Medicine Research. He
specialises in natural products, traditional medicine and
traditional anti-mosquito agents and health systems. We
are looking at encapsulating the lead traditional actives
for improved bioavailability.
6.4.4 Kenya Medical Research Institute (KEMRI) –
Kenya (through Dr Simon Ndirangu Muchohi)
Dr Muchochi is a research scientist with a strong
background in analytical techniques and procedures. He
is experienced in the development and validation of
analytical methods, chromatographic analysis of
biological samples, pharmacokinetics data analysis and
interpretation. We will work closely to ensure that the
clinical studies are performed in accordance with strict
scientific and regulatory guidelines in a timely and costeffective manner.
and acute immune response to orally administered
Chitosan and PEG coated PLGA nanoparticles.
Toxicology and Applied Pharmacology (In press. IF
3.359)
Boitumelo Semete, Lonji Kalombo, Lebogang Katata
and Hulda Swai. Nano-drug delivery systems: Advances
in TB, HIV and Malaria treatment, 2010. Book Chapter in
Smart Biomolecules in Medicine. VBRI Press (In press)
B Semete, L Booysen, Y Lemmer, L Kalombo, L Katata,
J Verschoor, and H Swai. In vivo evaluation of the
biodistribution and safety of PLGA nanoparticles as drug
delivery systems. Nanomedicine: Nanotechnology,
Biology, and Medicine (IF 5.44)
Lemmer, Y., Thanyani, S.T., Vrey, P.J., Driver, C.H.S.,
Venter, L., van Wyngaardt, S., ten Bokum, A.M.C.,
Ozoemena, K.I., Pilcher, L.A., Fernig, D.G., Stoltz, A.C.,
Swai, H.S. and Verschoor, J.A. 2009. Detection of
Antimycolic Acid Antibodies by Liposomal Biosensors.
Methods Enzymol 464: 80-102.
Swai, H., Semete, B., Kalombo, L., Chelule, P.K.,
Sievers, R. and Kisich, K. 2008. Nanotechnology in the
treatment of respiratory diseases. Journal of
Nanomedicine.
Swai, H., Chelule, P.K., Semete, B. and Kalombo, L.
2008. Nanotechnology in Drug Delivery for Malaria and
TB Treatment. In D.E. Reisner (ed) Bionanotechnology:
Global Prospects. Boca Raton: Taylor and Francis
Publishers.
Agbo, E.C., Agwale, S., Ezeugwu, C.O., Semete, B.,
Swai, H., Ikeme, A. and Somiari, R.I. Biotechnology in
Africa. Science Letters, Science:, 321, 26 September
2008
Semete, B., Kalombo, L., Chelule, P., Benadie, Y.,
Booysen, L., Katata, L., Naidoo, S. and Swai, H.S. 2008.
Novel nanoparticles for tuberculosis chemotherapy,
Science real and relevant: The 2nd CSIR Biennial
Conference, Pretoria, South Africa, 17-18 November
2008.
7. PUBLICATIONS (2008 to Present)
Semete B, Booysen, Kalombo L, Venter J.D, Katata L,
Ramalapa B, Verschoor J.A and Swai H. In vivo uptake
8
HULDA SWAI PhD
Research Group Leader- Encapsulation & Delivery
Polymers & Composites, Council for Scientific and Industrial Research
PO Box 395 Pretoria 0001 South Africa
Tel: +27 12 841 2366, Fax: +27 12 841 3553, Email: hswai@csir.co.za
TB Nanodrug Delivery Project Collaborations
9