Sulu Ortamda Radyasyonla Başlatılan Çapraz Bağlanma ile İnterpolimer Komplekslerden Nanojel Hazırlanması, Karakterizasyonu ve Farmasötik Kullanımı

Abstract

The size, surface charge and functionality of nanogels are the most important properties to be controlled for specific drug delivery applications. The size can be controlled by adjusting the experimental parameters (such as pH, molecular weight, solvent) applied during the formation of nanogels. Surface charge can be controlled by using cationic or anionic monomers or polymers in nanogels. Functionality can be introduced using chemical modification of already formed nanogels or polymers with specific functionalities. Functional groups are used to impart stimulus-responsive properties to nanogels. These structures are extremely important for the controlled release of bioactive species in targeted areas such as pH, temperature, ionic strength, electromagnetic field, light, etc. can be incorporated into the structure of nanogels so that they can respond to differences. It is possible to bring these three important features (size, surface charge and functionality) to the structure of nanogels with the approach of interpolymer complex (IPC) formation.

Poly(acrylic acid) (PAA) is a pH sensitive, biocompatible, hydrophilic and anionic polyelectrolyte. For these reasons, it has a wide range of use in drug delivery systems. Poly(N-vinylimidazole) (PVIm) is a weak polybase, polycation in water, hydrophilic, biocompatible and pH sensitive and it is widely used in drug carriers. Poly(N-vinyl pyrrolidone) (PVP) is one of the synthetic polymers approved by the FDA because it is non-ionic, biocompatible, biodegradable, and non-toxic and it is widely used in pharmaceutical and biomedical applications, as well as in the food industry. Due to these advantageous properties of PAA, PVP and PVIm, the interpolymer complexes formed by two of these polymers such as PAA-PVP and PAA-PVIm are quite promising for future nanogel synthesis. In this thesis study, the synthesis, BSA adsorption and drug carrier properties of biocompatible, functionalized interpolymer complex nanogels by the radiation-initiated cross-linking method were aimed.

Multifunctional PAA-PVP and PAA-PVIm interpolymer complex (IPC) nanogels by radiation-initiated crosslinking method were prepared without the use of any monomers, initiators, cross-linking agents, or other chemical agents. This method was preferred because it allows nanogels to be obtained with a greener chemistry protocol and to control the degree of crosslinking. Controlling the thermodynamics of aqueous solutions of PVP, PAA, and PVIm allows control of IPC coil sizes. Because IPC coils are the precursors of IPC nanogels to be obtained, spherical size control also enables the size control of nanogels. In this study, dilute solutions of PAA, PVP and PVIm in an acetone/water environment were prepared and IPCs prepared under different conditions (concentration, pH, molecular weight, addition order, mixing ratio, ionic strength, temperature, and acetone ratio) were investigated by Dynamic Light Scattering (DLS) technique. Interpolymer complexes were prepared by interacting PVP and PVIm solutions with PAA solution. The size distribution and complex stability of the prepared IPC samples were analyzed by DLS. In the second step, the prepared IPCs were exposed to radiation, yielding cross-linked interpolymer complex nanogels. Nanogel sizes were smaller than their constituent IPC coils as intra-coil crosslinking took place. IPC nanogels were obtained by irradiating the IPC coils at 3, 5, and 10 kGy in a 60Co gamma source with a dose rate of 0.022 kGy/h. After irradiation, shrinkage occurred due to the cross-links formed in the coils, and nanogels with wide size distribution (30-300 nm) and surface charge ranging between -7 and -44 mV were obtained. The effects of pH, temperature and ionic strength were investigated to control swelling and intra-coil crosslinking of synthesized IPC nanogels. After the size control of the irradiated IPC nanogels was achieved, they were characterized using DLS, Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM). The synthesized IPC nanogels were loaded with curcumin to obtain a drug carrier system in the presence and absence of BSA, and their release studies were investigated.