Injectable biodegradable polymeric system for preserving the active form and delayed-release of camptothecin anticancer drugs

Mert, Olcay
Demir, Ayhan Gürbüz
One of the most challenging problems for camptothecin (CPT) family anticancer drugs (i.e. topotecan (TPT)) is the conversion of the active lactone ring into an inactive toxic carboxylate form under physiological conditions (pH = 7.4) in the body. Therefore, a simple platform based on thermosensitive PLLA-mPEG gels was designed to maintain TPT and CPT in lactone form, especially for brain tumor therapies. A high stabilization of the lactone species CPT and TPT within gel (>95%), efficient versatile homogenous drug loadings at 0.015%, 1%, and 10%, and the sustained-release of CPT and TPT over three weeks were all successful. The stabilization mechanism of drugs with gel was elucidated by ATR-FTIR, confocal and light microscopy. The cytotoxic efficacy of TPT in the PLLA-mPEG platform (PLLA-mPEG-TPT) was evaluated on LLC-1 and 4T1 cancer cell lines. In vivo, the administration of PLLA-mPEG-TPT to mice with breast tumors resulted in a significant reduction in tumor size and better survival percentages.


Immobilization of glucose oxidase and urease in hydrogel matrices
Gurel, I; Arica, MY; Hasırcı, Vasıf Nejat (1997-01-01)
Immobilization of glucose oxidase and urease in hydrogels of 2-hydroxyethyl methacrylae, and N-vinyl pyrrolidone (NVP) was achieved by irradiation (using UV kand gamma-rays). The effect of radiation on entrapment efficiencies, retention of activities and swelling rates was obtained. To optimize the system, duration of exposure, reaction temperature, co-monomer concentrations, initiator and cross linker compositions were varied. The repeated reusability of the generated products was also tested. It was found...
Chemoenzymatic synthesis of (1S,2R)-1-amino-2-indanol, a key intermediate of HIV protease inhibitor, indinavir
Demir, AS; Hamamcı, Haluk; Doganel, F; Ozgul, E (2000-04-21)
The synthesis of (1S,2R)-1-amino-2-indanol, a key component of HIV protease inhibitor is accomplished in four steps starting from indanone efficiently and with high levels of diastereo- and enantioselectivity. The starting material is converted into 2-acetoxy-1-indanone involving Manganese (III) acetate oxidation. The 2-acetoxyketone is hydrolyzed to 2-hydroxy-1-indanone enantioselectively using Rhizopus oryzae. Selective reduction of 2-hydroxyoxime derivative, derived from the 2-hydroxyketone, gives the am...
Structural effects of simvastatin on liver rate tissue: Fourier transform infrared and Raman microspectroscopic studies
Garip, Sebnem; Bayari, Sevgi Haman; Severcan, Mete; Abbas, Sherif; Lednev, Igor K.; Severcan, Feride (2016-02-01)
Simvastatin is one of the most frequently prescribed statins because of its efficacy in the treatment of hypercholesterolemia, reducing cardiovascular risk and related mortality. Determination of its side effects on different tissues is mandatory to improve safe use of this drug. In the present study, the effects of simvastatin on molecular composition and structure of healthy rat livers were investigated by Fourier transform infrared and Raman imaging. Simvastatin-treated groups received 50 mg/kg/day simva...
Development of a novel zebrafish xenograft model in ache mutants using liver cancer cell lines
Avci, M. Ender; Keskus, Ayse Gokce; Targen, Seniye; Isilak, M. Efe; Ozturk, Mehmet; Atalay, Rengül; ADAMS, MİCHELLE; KONU KARAKAYALI, ÖZLEN (2018-01-25)
Acetylcholinesterase (AChE), an enzyme responsible for degradation of acetylcholine, has been identified as a prognostic marker in liver cancer. Although in vivo Ache tumorigenicity assays in mouse are present, no established liver cancer xenograft model in zebrafish using an ache mutant background exists. Herein, we developed an embryonic zebrafish xenograft model using epithelial (Hep3B) and mesenchymal (SKHep1) liver cancer cell lines in wild-type and achesb55 sibling mutant larvae after characterization...
Synthesis of Some Substituted 6-Phenyl Purine Analogues and Their Biological Evaluation as Cytotoxic Agents
Kucukdumlu, Asligul; Tuncbilek, Meral; Guven, Ebru Bilget; Atalay, Rengül (2017-01-01)
A series of 6-(4-substituted phenyl)-9-(tetrahydropyran-2-yl) purines 3-9, 6-(4-substituted phenyl) purines 10-16, 9-((4-substituted phenyl) sulfonyl)-6-(4-substituted phenyl) purines 17-32 were prepared and screened initially for their in vitro anticancer activity against selected human cancer cells (liver Huh7, colon HCT116, breast MCF7). 6-(4-Phenoxyphenyl) purine analogues 9, 16, 30-32, had potent cytotoxic activities. The most active purine derivatives 5-9, 14, 16, 18, 28-32 were further screened for t...
Citation Formats
O. Mert, G. ESENDAĞLI, A. DOĞAN, and A. G. Demir, “Injectable biodegradable polymeric system for preserving the active form and delayed-release of camptothecin anticancer drugs,” RSC ADVANCES, pp. 176–185, 2012, Accessed: 00, 2020. [Online]. Available: