Download Ph. D Project Proposal for IGS @ NITHM

NANYANG INSTITUTE OF TECHNOLOGY IN HEALTH & MEDICINE
Ph. D Project Proposal for IGS @ NITHM
Each proposal must satisfy the following requirements:
1) One Supervisor and one Co-Supervisor (Co-Supervisor must be from another School; can be Adjuncts)
2) One clinician collaborator is highly recommended
3) Length of proposal should be capped within 2 pages
Programme:
Diagnostic Medical Devices
X-omics
Therapeutic Medical Devices
Medical Imaging and Signal Analysis
x Nanomedicine
Tissue Engineering
Drug Discovery, Systems Biology and Synthetic Biology
Health Systems Complexity
Project Topic:
Bioactivity and controlled release studies of proteins in nanocarriers
Supervisor:
Subbu Venkatraman
School/College:
MSE
Co-Supervisor:
Peter Preiser
School/College:
SBS
Clinician
Collaborator:
Tina Wong
Institution:
SERI
Is research funding available for the project?
x Yes
No
SCOPE OF THE PROJECT
Present scope of the project that the student will address
For retinal diseases, included macular degeneration, anti -angiogenesis factors are injected
intravitreally to the back of the eye, using a painful inject ion that sometimes also leads to
infections. Our approach is to use nanocarriers encapsulating the anti -angiogenesis factor, as a
sub-conjuctival injection, followed by transport across the sclera to the back of the eye. While
other researchers will focus on trans-scleral transport studies, this student will work on
maximizing the loading of the protein into the nanocarriers, as well as controlling the release of
the protein from the carriers. This is to be accomplished by enhancing the interaction of the
protein with the carrier molecules; such interactions include electrostatic, hydrogen -bonding as
well as hydrophobic interactions. As the carriers are based on liposomes, and polyelectrolyte coated nanoparticles, the composition of the liposomal molecules as well as of the polyelectrolyte
will be varied to maximize the interactions, which could also be influenced by the pH. Active
methods of loading the proteins into the core of the liposome will be explored. For the
nanoparticles, we will attempt to load t he core using double-emulsion methods. Both of these
approaches will have different effects on the protein bioactivity, which will be assessed by
existing methods.
Factors affecting the release of the encapsulated protein will be studied using standard in vitro
methodologies. We will also assess the bioactivity of the released protein. Based on the
compositions and the interactions (assessed via iso -thermal calorimetry) we will formulate a
model to predict the release behaviour.
STATAMENT OF NEED
Describe medical problem that the project will attempt to address
Age-related macular degeneration is characterized by the growth of unwanted blood vessels in the
retina, in the case of the so-called wet version of AMD. This is the predominant version, and is
currently treated with intra-vitreal injections of anti-angiogenesis factors (bevacizumab and
ranibizumab; which are vastly different in molar mass). The intra-vitreal injections are painful
and not patient-friendly, and need to be repeated at 3-month intervals. There is a clear need for a
less-invasive option for the patient, which also needs to be a sustained therapy (not daily
administration). The availability of this option for the patients will in all likelihood increase the
number of patients opting for treatment of the condition, even if it means somewhat more frequent
doctor visits.
PROPOSED SOLUTION
Describe proposed solution to the medical problem
Our proposed solution is a formulation of the anti -angiogenesis factor that may be delivered via the
more friendly, less invasive sub-conjuctival injection. The approach is to encapsulate the protein
into nano-sized carriers for sub-conjuctival injection. The carriers may release some of their payload
in the sub-conjuctival space and the released protein can be transported trans-sclerally into the
posterior segment of the eye. It is also likely that some of the carriers are transported trans-sclerally
with intact payload. For the purposes of the therapeutic benefit, either way of getting the protein to
the back of the eye is acceptable. However, the duration of the therapeutic effect will vary
depending on how the protein is transported across the sclera (ie, as a protein molecule or
encapsulated). This project will study the release kinetics and bioactiv ity of the released protein
from various carriers, and correlate them to trans -scleral transport kinetics.