Analysis of insulin conjugation reactions with carrier polymers

Bioconjugation includes combining different properties of two or more molecules to form a new complex. Recently, materials science has focused on softer materials such as polymers. Since the desired modification on the polymer is controlled and easy, polymers are used in various biological applications. Polymers are used in various medical applications such as drug release, antigen release, tissue engineering and also in many applications of biotechnology. Insulin plays a central role in glucose metabolism in the body. Because the traditional methods for diabetes arising due to inadequacy of insulin activity is inadequate, researchers focus on new methods to improve activity. Since parenteral administration is the only route for insulin treatment, it has been extensively investigated new routes such as oral, nasal, rectal, pulmonary and ocular. Bioconjugation of insulin with anionic polymers or encapsulation of insulin in biodegradable nano and micro structures such as nanocapsules, nanospheres or microspheres is considered the methods to enhances the insulin activity. In scope of this thesis, it was designed controlled drug delivery system forming insulin bioconjugates with different polymers for diabetes treatment. Accordingly, it was used two different polymers: (i) First, a linear anionic polymer, PAA, is the one of the most popular mucoadhesive poymer due to its high mucoadhesive functionality, low toxicity especially with low molecular weight. (ii) Secondly, poly ( lactic -co -glycolic acid) ( PLGA) polymer is used as a controlled and sustained drug delivery system with continous effect from one week to several months. PLGA is preferred to overcome problems such as multiple injections and high toxicity and provide the desired therapeutic effect by protecting the molecules with short in vivo half- life. In this thesis study, it was synthesized covalent bioconjugate of insulin and polyacrylic acid and obtained insulin nanoparticles using poly(lactic-co-glycolyc acid). The obtained bioconjugates were analysed with GPC, UV spectrophotometry, Zetasizer, Fluorescence spectrophotometry. Insulin nanoparticles formed by poly(lactic-co-glycolyc acid) polymers were analysed with Zetasizer and FTIR. Nanoparticle formation was investigated with Atomic Force Microscobe. In this thesis study, it aims to provide an insight for future studies related to insulin controlled drug release systems using insulin-polymer bioconjugates and nanoparticles designed with linear polymer and polymeric nanoparticles.