Antiretroviral İlaç Baskılanmış Polimerik Nanopartiküllerin Hazırlanması, Karakterizasyonu ve Nazal Salınım Sistemlerde Kullanılması

Abstract

The superior properties of molecularly imprinted polymers, such as stereospecific recognition, have recently brought their use in biomedical applications such as drug release. Nasal controlled release systems are an effective treatment method based on delivering the drug to the target tissue by using the therapeutic effect at the optimum dose, at the right time and at the right place. Drug delivery via the nasal release system is an advantageous method because of its slightly acidic pH and low enzymatic activity in this region. Biomaterials used in the preparation of controlled release systems are polymeric systems that can be obtained naturally or synthetically and their varieties are increasing day by day. One of these systems is nanoparticles. Thanks to their superior properties, nanoparticles are used as biomaterials in many studies. Due to the adhesiveness of the mucosa, hydrophilic nanoparticles play an important role in the nasal release of desired molecules. Mucoadhesive nanoparticle systems improve mucosal absorption as they bind strongly to the mucosa and increase the viscosity of mucin. Thus, they significantly reduce the nasal mucociliary clearance rate and thus prolong the residence time of the formulation in the nasal cavity. In this direction, it is aimed to synthesize RTV-imprinted nanoparticles and use them in nasal release systems within the scope of the thesis. In the first stage of the thesis, MATrp- RTV complex was formed and RTV imprinted poly(HEMA-MATrp) nanoparticles were synthesized by mini-emulsion polymerization. In addition, non-imprinted nanoparticles were synthesized without the template molecule Ritonavir. In the second stage of the thesis, the characterization of the synthesized nanoparticles was carried out with the help of FTIR, SEM, Zeta Size Analysis and surface area calculations. As a result of Zeta size analysis, the average size of Ritonavir (RTV) imprinted nanoparticles was 88.46 nm and its polydispersity was measured as 0.279. The specific surface area of the MIP nanoparticle was found to be 628.34 m2/g. In the third stage of the thesis, studies on the release of Ritonavir under in vitro conditions were carried out and the amount of RTV released was determined using UV spectrophotometer. The effects of pH, temperature and concentration parameters on drug release behavior were observed. The release study was kinetically examined and it was determined that the drug release is a release that complies with the Korsmeyer-Peppas law and is suitable for controlled release. In the last part of the thesis, as a result of the analyzes performed in cytotoxicity studies (MTT test), it was observed that the synthesized nanoparticles did not show any cytotoxicity in living cells. This study demonstrated that RTV imprinted nanoparticles are a fast, sensitive and controlled analysis method for the use of nasal release systems.