NANYANG INSTITUTE OF TECHNOLOGY IN HEALTH & MEDICINE
Ph. D Project Proposal for Skin Research Programme
Please choose either Section (A) or (B) as applicable:
(A) For School-based Research Programme
Project Topic:
Supervisor:
Name, (Title)
School:
Name, (Title)
School:
Co-Supervisor:
(if any)
(B) For Future Healthcare Thematic Research Programme at Interdisciplinary Graduate School
Project Topic:
Supervisor:
Co-Supervisor:
2
nd
Topical delivery of systemic therapeutic agents for use in skin inflammatory
disorders.
Prof Subbu Venkatramann
School:
Name, (Title)
School:
Name, (Title)
Institution:
Dr Steven Thng Tien Guan
Institution:
Co-Supervisor:
(if any)
Clinician Collaborator:
(if any)
Is research funding available for the project?
If yes, please specify:
Yes
National Skin Centre
No
Awaiting outcome of skin thematic grant call.
SCOPE OF THE PROJECT
Present scope of the project that the student will address
The student will attempt to formulate a topical version of methotrexate, an oral anti -inflammatory agent,
for topical use for common conditions like eczema, psoriasis and vitiligo. The scope of work would
include:1. Design a delivery system that stays on the skin for a reasonable period (1 day at least), delivers the drug to the dermis
(preferably not into the systemic circulation) and sustains the delivery for at least 1 day. The delivery system can be in
creams form (preferably) or patch form and with a successful development of the cream/patch, the student will proceed to
step 2.
2. Design a set up to study the depth of penetration of the drug over time. For this, the student can use organotypic skin
cultures (developed by NTU researchers at SBS and MSE) rather than cadaver skin, which is in short supply. In order to
minimize skin usage, we have cocnpetualized a in vitro system based on the Boyden chamber (traditionally used for
Aug 2014 Intake
transport studies of cells).
3. Evaluation of creams and patches; localized irritation/sensistization in a suitable animal model before proceeding to
human trial.
STATEMENT OF NEED
Describe medical problem that the project will attempt to address
Inflammatory skin diseases, like psoriasis and eczema, have high prevalence rates in Singapore as well as
globally and skin dermatitis and psoriasis, together constitutes the most common skin disorders seen in the
National Skin Centre with close to 400 patients seeking treatment at the National Skin Centre daily. Treatment
of these conditions remain difficult, needing prolonged therapy with topical immunomodulators.
Currently, there are only 2 families of topical immunomodulators, topical steroids and topical calcineurin
inhibitors, for the management of these common skin inflammatory conditions.
Topical steroids are the mainstay of therapy for these group of disease but not all cases respond to topical
steroids, regardless of their strength. In addition, there are potential side effects of striae, skin thinning,
telangiectasias and even cushings syndrome on prolonged and these, together with steroid phobias of some
patients, limits their use. Topical calcineurin inhibitors like Tacrolimus and Elidel are useful substitutes but they
are expansive and are not as effective as topical steroids.
There is a certainly a need for better and safer topical immunomodulator for patients who do not respond to
topical steroids/calcineurin inhibitors or develop side effects from them. Oral Methotrexate has been used for
many years to treat extensive psoriasis as well as for eczema, with good effectiveness. In fact, oral
Methotrexate is used when patients fail standard topical therapies. However, oral methotrexate does have
significant side effects of bone marrow suppression and liver toxicity requiring clinicians to perform blood tests
frequently to pick up these adverse effects early and stop them early when necessary.
PROPOSED SOLUTION
Describe proposed solution to the medical problem
Aug 2014 Intake
The proposed solution would be to try to formulate methotrexate for topical application. Because of its good
effectiveness and potential toxicity when taken orally, there had been quite a few attempts 10-15 years ago to
formulate Methotrexate in a topical form to be applied. All previous attempts were not successful and there has
not been a trial to formulate topical Methotrexate for the last 10 years 1,2. With the advancement in drug delivery
systems using topical liposomes or nanoemulsions, and coupled with Prof Subbu’s expertise in advanced drug
delivery systems, it is timely now to revisit this idea and to try to solve a challenge in existence for so many
years.
Successful formulation of topical methotrexate with good clinical efficacy for common inflammatory skin
conditions like eczema and psoriasis would provide clinicians another option for the management of these
common but difficult to treat conditions. It will offer patient better chances of control without the accompanying
side effects. If successful, there will be a huge commercial interests for this product and the potential market for
topical methotrexate is immense as these inflammatory skin conditions affect at least 10-15% of population
worldwide.
Aug 2014 Intake