Synthesis and characterization of targeted mucoadhesive delivery systems in nanobiotechnology

The most important advantages of the mucoadhesive drug delivery systems are to provide increased permeability of drug into the systemic circulation and bioavailability of the drug. Therefore, mucoadhesive polymers, which were extensively used as drug delivery systems via mocasal membranes, besides being non-toxic, biocompatible and economical must possess some molecular characteristics required to develop an effective and safe mucoadhesive drug delivery system. In this thesis study, it was aimed that synthesis and characterization of the novel biocompatible, biodegradable, non-toxic, mucoadhesive drug carrier systems, which have suitable characteristics for drug carrying via mucosal membrane, and preparation of their nanoformulations and investigation of their properties. For this purpose, firstly, Chitosan (Chi), which is a biopolymer frequently used as drug carrier in the pharmaceutical applications, was depolymerized to obtain low molecular weight Chi product (DChi). To obtain the palmitoyl chitosan (DChi-PA), DChi was modified with palmitic acid (PA), which has high interaction with cell membrane, and characterized for the first time. Then, to gain the mucoadhesiveness to DChi-PA product, its conjugate TGA-DChi-PA was synthesized by the reaction with thioglycolic acid (TGA) and characterized, for the first time. Nanoparticle formulations of the products were prepared by ionic gelation method, their in vitro cytotoxicity analysis and mucoadhesion properties were evaluated. Characterization of the molecular structures of the products were realized by Fourier Transform Infrared Spectroscopy (FTIR) and Proton Nuclear Magnetic Resonance Spectroscopy (1H NMR) analyses. The amount of thiol group in the structure of the TGA-DChi-PA product was determined by iodimetric titration method. Characterization of the nanoparticle formulations of the products were realized using Dynamic Light Scattering Analysis (DLS) method by measuring their particle size (nm), polydispersity index (PDI) and zeta potential (mV) values. In vitro cytotoxicity properties were investigated by using MTT assay on human embryonic kidney cell line (HEK293). The mucoadhesion properties of the products were evaluated by Texture analysis method with two separate applications on ex vivo sheep nasal mucosal membrane and in vitro 0.20 µm cellulose acetate membrane filter. The evaluation of nanoparticle formulations was evaluated by the retention/rinse method of nanoparticles on the ex vivo sheep nasal mucosal membrane surface. As a result of the ex vivo and in vitro applications carried out in this thesis study, it was observed that the new DChi-PA(1:0,25) product increased mucoadhesion in addition to its cell penetration enhancing effect and that the new TGA-DChi-PA(1:0,25) conjugate synthesized by adding the thiol group to the structure further improved the mucoadhesiveness property. In conclusion, it is obvious that the nanoparticle formulation based on TGA-DChi-PA(1:0,25) synthesized in this study for the first time, will be great importance as a biocompatible non-toxic mucoadhesive nanocarrier via mucosal membrane in the nanobiotechnology.