טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentDavidovich-Pinhas Maya
SubjectToward New Applications of Mucoadhesive Polymers
DepartmentDepartment of Chemical Engineering
Supervisors Professor Havazelet Bianco-Peled
Dr. Offer Harari


Abstract

When the conventional fertilization treatment options failed, women are referred to In Vitro Fertilization (IVF). Unfortunately, the yield of each treatment is still low. Researches suspect that weak interactions of the embryo with the uterus could lead to its expulsion during uterus contractions. Therefore, improving the adhesion between the embryo and the uterus could, potentially, improve the success rate in IVF. We will attempt to establish a novel approach for this proposes by “gluing” embryos to the uterus using mucoadhesive polymers, polymers which are known in their ability to adhere to mucus gel layer. As a model, we have chosen an anionic polymer called alginate, from which tablets for encapsulating the fertilized egg were prepared. We found that alginate gel is a good local environment for fertilized egg which allows cell growth and development by encapsulating fertilized egg of Denis fish in it.

The adhesion properties of alginate were examined using tensimeter assay. In order to mimic the uterus surface we used several synthetic and natural surface models. The results of the adhesion assays involving the synthetic surface model suggested that the adhesion strength is correlated with the calcium concentration in the tablet. In addition, we have found that there is a correlation between the adhesion strength and the polymer concentration. Increasing the polymer and the calcium concentration has led to an increase in the adhesion strength.

Since the adhesion strength of alginate to all surfaces was not high enough, we have modified the alginate by attaching cysteine residence to the polymer backbone, a modification which could potentially create di-sulfide bridges with the mucin groups in the uterus. In order to verify that the synthesis lead to the desirable product, NMR, FTIR and rheology measurments were employed. We have found that the adhesion strength of alginate to both surfaces is larger then that of the modified alginate. Yet, the alginate-thiol had better adhesion to the improved synthetic model, which contain mucin molecules,  which points on a possible sulfide bridge interactions.

The swelling behavior of both materials, alginate and modified alginate, was examined. We found that both materials either swell or shrink depending on the calcium concentration. When comparing the alginate's swelling ratio to a theoretical model, modified to meet the specification of our experiments, we found a good agreement. On the contrary, the swelling of alginate-thiol could not be predicted from the theoretical model.