pH güdümlü nano ilaç taşıyıcı bir sistem olarak nanosponge eldesi, karakterizasyonu in vitro ilaç salınım ve toksisite özelliklerinin araştırılması

Thesis aimed to fabricate and investigate usability of ALD-NS as a pH responsive drug delivery agent. For this aim, functionalized β-CD with aldehyde (CHO) groups were fabricated by oxidation process using varying molar ratios of NaIO4 and characterization results confirmed formation of OX-β-CDs with functional CHO groups. OX-β-CDs was crosslinked with PMDA crosslinker to obtain water soluble, solid ALD-NS with the method developed and DOX.HCl due to the presence of NH2 group was integrated by reflux method, aiming to ensure both pH sensitive Schiff base (C=N) bond and hydrophilic part of the ALD-NS. ALD-NS+DOX was characterized, and results showed this formation, encapsulation, and morphological change with PS (372.7±8.21nm), negative ZP (-12.8±1.54), high EE (85.5%). In vitro release behavior of ALD-NS+DOX was evaluated in three buffer conditions at different pH and observed that drug release at pH 5.2 is higher than at pH 7.4 environment occurring, sustain, prolong drug release profile compared to pure DOX due to easy hydrolysis of Schiff base and crosslinker. Time and dose dependent cytotoxicity and cellular uptake of ALD-NS+DOX were determined on A549 cancer cells. Cell viabilities of drug loaded NC decreased with increasing the concentration but have found higher viabilities and displayed the intensive drug accumulation on the surface or inside of the cell compared to free DOX in the all-equivalent concentration at various time range. Drug release kinetics was best expressed by the Krosmeyyer-Peppas model based on the highest correlation coefficient (R2=0.97), revealing that diffusion coefficient "n" was found 0.622 for PBS and 0.71 for NaAcetate at pH 5.2 specifying drug release occurs due to both dissolution (hydrolysis of Schiff base) and non-Fickian diffusion. As a result, the novel kind of functionalized nanostructure has the potential to be a candidate drug carrier in a low pH environment, especially for drugs containing NH2 side group.