טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentLufton Maayan
SubjectLiving Bacteria in Thermo-Responsive Gel for Treating
Fungal Infections
DepartmentDepartment of Biotechnology and Food Engineering
Supervisor Professor Boaz Mizrahi
Full Thesis textFull thesis text - English Version


Abstract

Fungal infections are a significant and growing public health concern infecting billions of people every year. Most people will suffer from fungal infections during their lifetime. As of today, Candida is the most common fungal infection in the world. The infection can emerge on skin, nail, mucosal tissues such as oral and genital and as a systemic disease.  This research focuses on skin fungal infection. Current pharmacological anti-fungal treatment includes the Azole family. The Azole group of drugs has added greatly to the therapeutic options but they have several drawbacks including intolerance by many patients due to adverse effects (e.g. fever, chills and headaches) and more importantly, they are associated with significant liver and kidney toxicities which limit its use. In addition, these drugs should be applied daily and for over a year until an improvement is noticed. Moreover, Candida strains which are resistant to current treatments have been found, necessitating the need for new therapeutic strategies.

Here we have developed an innovative system based on a live organism based formulation which functions as a small “factory” that continuously produces anti-fungal agents and deliver it in-situ.  The production and in-situ delivery of anti-fungal agents was facilely achieved by incorporating the following: (1)  F-127- a thermoresponsive polymer  with lower critical solution temperature (LCST) at 32°C -35°C and (2) Bacillus subtilis- Gram-positive bacteria, naturally found on human skin and generally regarded as safe (GRAS).  Bacillus subtilis naturally produces and secretes a variety of antifungal agents. The resulting formulation should be easy to administer (e.g., liquid at room temperature or under refrigerating) but quickly solidifies on the skin after administration.

After performing viability assay, we found the polymer to be harmless to the bacteria. In addition, the formulation penetrates into the epidermis layer, without penetrating the inner dermis layer. Finally, an in vivo test performed on mice, showed that the new formulation is able to treat local fungal skin infection and encourage the recovery of the affected area.

In this research, a new delivery system of live food grade bacteria, incorporated in a thermoresponsive polymer, is presented. This system was found to be effective in inhibiting skin fungal infection by naturally releasing anti-fungal agents on top of the treated area.