LEE- Yenilikçi Teknik Tekstiller Lisansüstü Programı

Bu topluluk için Kalıcı Uri

http://hdl.handle.net/11527/19497

Gözat

Konu "drug release" ile LEE- Yenilikçi Teknik Tekstiller Lisansüstü Programı'a göz atma
  • Öge
    Fabrication, characterization and drug release behaviors of electrospun PEtOx/Flubendazole nanofibrous webs
    (Graduate School, 2024-07-11) Sürücü, Elif ; Eniş, İpek Yalçın ; 503201827 ; Innovative Technical Textiles
    Filarial infections in humans result in deteriorating health conditions for over a hundred million people, particularly in some low-income countries in Africa and Asia, notably sub-Saharan Africa. They lead to diseases like lymphatic filariasis and onchocerciasis, with 120 million people currently afflicted by this disease. Flubendazole is the most appealing benzimidazole drug for the treatment of filarial parasites. It is also licensed and marketed in Europe as Fluvermal to treat intestinal nematodes in humans. However, it is a benzimidazole methylcarbamate anthelmintic with poor water solubility and is included in the Biopharmaceutics Classification System (BCS) class IV compound. For this reason, it has poor solubility in the aqueous systems formed in the gastrointestinal tract, shows poor absorption in the blood circulation and therefore its bioavailability is extremely low. These drawbacks can be deal with by the use of amorphous solid dispersions (ASD), which is a promising approach to improve the oral bioavailability of poor water-soluble drugs. ASDs prepared with water-soluble polymeric carriers are used to enhance the dissolving ratio and potentially bioavailability of such hydrophobic drugs. Electrospun nanofiber-containing ASDs possess exceptional physical stability due to the molecular distribution of the drug within the fibers, and the polymer chains provide a steric barrier against the recrystallization of the drug. Further, it improves drug dissolving rates in aqueous conditions due of their three-dimensional construction and high interconnected porosities with configurable pore sizes, allowing for effective surface functionalization. The solvent used to prepare polymeric solutions has a crucial impact on achieving extremely high drug loading and electrospinnability. Over the past decades, poly(2-ethyl-2-oxazoline) (PEtOx) has found application as a polymer in biomedical and pharmaceutical fields, particularly for delivering hydrophobic drugs, proteins, and nucleic acids. It has exceptional biocompatibility, lack of toxicity and anti-fouling properties. Furthermore, various researches on PEtOx have stated that PEtOx has great stability in body, and no tissue destruction, being the polymer safe for use for body. In this thesis, ASDs were developed and fabricated by loading PEtOx with 40%, 45%, 50%, or 55% wt. flubendazole using the electrospinning method. The resulting nanofiber membranes were examined in detail in three different surface forms. Physical, morphological, and thermal characterizations of the surfaces were conducted, and the effects of using PEtOx, flubendazole ratio, and surface form on in-vitro drug release behaviors were investigated. Scanning Electron Microscope (SEM) analysis showed that homogeneous and continuous fibers were obtained on the membrane surfaces regardless of the flubendazole ratio. Crimped fibers were observed in the samples with the cut surface form, while flattened fibers were seen in the ground samples. The fiber diameter measurements indicated that the fiber diameter tended to increase with a higher flubendazole ratio, and although no difference was observed in the cut samples, flattening was noted in the grinded samples. When examining the results of Differential Scanning Calorimetry (DSC) analysis, it was found that glass transition temperature (Tg) values were between the Tg of pure flubendazole and PEtOx. This indicates that both components are blended at a molecular level. On the other side, it was found that Tg values increased with the flubendazole ratio, regardless of the surface form. The surface form did not show a significant affect on Tg values. Evaluating the drug release profiles revealed that the release rate was decreased by the increasing flubendazole ratio, whereas the fastest release obtained in the cut surface form. Additionally, while crystalline flubendazole achieved a release rate of 2.12 mg/mL at the 60-minute mark, the ASDs produced with different flubendazole concentrations exhibited drug release in the range of 7.46-14.48 mg/mL which showed that PEtOx loaded with flubendazole exhibited a higher release amount. In this context, it is thought that ASD systems developed within this thesis represent an innovative design with promising potential for the release of poorly soluble drug.