Akademik Veri Yönetim Sistemi
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, cilt.77, 2022 (SCI-Expanded)
In the current study, polyethylene glycol-block-poly(epsilon-caprolactone) (PEG-block-PCL) nanocarriers of lonid-amine which is an indazole-3-carboxylic acid derivative anticarcinogenic agent, were designed and optimized through response surface type 32 full factorial design based DoE approach. Optimization process was imple-mented to find out the impact of the experimental factors, Vitamin E TPGS percentage and lonidamine/PEG-block-PCL mass ratio, on two particle features: encapsulation efficiency and particle size. Lonidamine encap-sulated polymeric based nanocarriers were evaluated with regards to polydispersity index, zeta potential, morphological and thermal characteristics, in vitro release profiles, stability performance, cell viability, cell cycle arrest, migration and apoptosis experiments. The encapsulation efficiency values of the nanocarriers were found between 73.72% and 93.50%. The particle size of nanoparticles ranged between 149.3 and 568.1 nm with a wide polydispersity index. The lonidamine encapsulated PEG-block-PCL nanocarriers that had the configuration of 0.030% of Vitamin E TPGS amount and 1/10 mass ratio of Lonidamine/PEG-block-PCL were selected as the optimized PEG-block-PCL nanocarrier system based on the response surface type 32 full factorial design and the desirability function method. The optimized nanoformulation had a spherical shape with 87.52% encapsulation efficiency value and 180.1 nm particle diameter. Cell uptake studies indicated the efficient internalization and high uptake performance of the optimized nanocarriers into the SW480 colon cancer cells. The optimized nanoparticles decreased viable cell amount significantly when compared to lonidamine alone and induced an arrest of cell cycle at G0/G1 phase. The annexin V binding experiments also demonstrated that the optimized nanoparticles induced apoptosis of SW480 cells in accordance with other findings. In conclusion, the results obtained from this research indicated that the vitamin TPGS decorated PEG-block-PCL nanocarriers of lonid-amine can be presented as a promising treatment strategy for colon cancer.