Browsing by Author "Li, Weikun"

Now showing 1 - 2 of 2

Pharmacokinetics, biodistribution, and anti-angiogenesis efficacy of diamino propane tetraiodothyroacetic acid-conjugated biodegradable polymeric nanoparticle (Retracted Article)
(Nature, 2019-06-21) Li, Weikun; Bharali, Dhruba J.; Lin, Qishan; Godugu, Kavitha; Fujioka, Kazutoshi; Keating, Kelly A.; Mousa, Shaker A.; Yalçın, Murat; Bursa Uludağ Üniversitesi/Veteriner Fakültesi/Fizyoloji Anabilim Dalı.; 0000-0002-5600-8162; AAG-6956-2021; 57192959734
The anti-angiogenic agent, diamino propane tetraiodothyroacetic acid (DAT), is a thyro-integrin (integrin alpha v beta 3) antagonist anticancer agent that works via genetic and nongenetic actions. Tetraiodothyroacetic acid (tetrac) and DAT as thyroid hormone derivatives influence gene expression after they transport across cellular membranes. To restrict the action of DAT to the integrin alpha v beta 3 receptors on the cell surface, we used DAT-conjugated PLGA nanoparticles (NDAT) in an active targeting mode to bind to these receptors. Preparation and characterization of NDAT is described, and both in vitro and in vivo experiments were done to compare DAT to NDAT. Intracellular uptake and distribution of DAT and NDAT in U87 glioblastoma cells were evaluated using confocal microscopy and showed that DAT reached the nucleus, but NDAT was restricted from the nucleus. Pharmacokinetic studies using LC-MS/MS analysis in male C57BL/6 mice showed that administration of NDAT improved the area under the drug concentration curve AUC(()(0-)(48 h)) by 4-fold at a dose of 3 mg/kg when compared with DAT, and C-max of NDAT (4363 ng/mL) was 8-fold greater than that of DAT (548 ng/ mL). Biodistribution studies in the mice showed that the concentrations of NDAT were higher than DAT/Cremophor EL micelles in heart, lung, liver, spleen, and kidney. In another mouse model using female NCr nude homozygous mice with U87 xenografts, tumor growth was significantly decreased at doses of 1 and 3 mg/kg of NDAT. In the chick chorioallantoic membrane (CAM) assay used to measure angiogenesis, DAT (500 ng/CAM) resulted in 48% inhibition of angiogenesis levels. In comparison, NDAT at low dose (50 ng/CAM) showed 45% inhibition of angiogenesis levels. Our investigation of NDAT bridges the study of polymeric nanoparticles and anti-angiogenic agents and offers new insight for the rational design of anti-angiogenic agents.
Self-assembly of green tea catechin derivatives in nanoparticles for oral lycopene delivery
(Elsevier, 2017-02-28) Li, Weikun; Lin, Qishan; Ardawi, Mohammed-Salleh M.; Mousa, Shaker A.; Yalçın, Murat; Uludağ Üniversitesi/Veteriner Fakültesi/Fizyoloji Anabilim Dalı.; 0000-0002-5600-8162; AAG-6956-2021; 57192959734
Lycopene is a natural anti-oxidant that has attracted much attention due to its varied applications such as protection against loss of bonemass, chronic diseases, skin cancer, prostate cancer, and cardiovascular disease. However, high instability and extremely low oral bioavailability limit its further clinical development. We selected a green tea catechin derivative, oligomerized (-)-epigallocatechin-3-O-gallate (OEGCG) as a carrier for oral lycopene delivery. Lycopene-loaded OEGCG nanoparticles (NPs) were prepared by a nano-precipitation method, followed by coating with chitosan to form a shell. This method not only can easily control the size of the NP to be around 200 nm to improve its bioavailability, but also can effectively protect the lycopene against degradation due to EGCG's anti-oxidant property. OEGCG was carefully characterized with nuclearmagnetic resonance spectroscopy and mass spectrometry. Lycopene-loaded polylactic-co-glycolic acid (PLGA) NPs were prepared by the same method. Chitosan-coated OEGCG/lycopene NPs had a diameter of 152 +/- 32 nmand a.-potential of 58.3 +/- 4.2 mv as characterized with transmission electron microscopy and dynamic light scattering. The loading capacity of lycopene was 9% and encapsulation efficiency was 89%. FT-IR spectral analysis revealed electrostatic interaction between OEGCG and chitosan. Freeze drying of the NPs was also evaluated as a means to improve shelf life. Dynamic light scattering data showed that no aggregation occurred, and the size of the NP increased 1.2 times (S-f/S-i ratio) in the presence of 10% sucrose after freeze drying. The in vitro release study showed slow release of lycopene in simulated gastric fluid at acidic pH and faster release in simulated intestinal fluid. In an in vivo study in mice, lycopene pharmacokinetic parameters were improved by lycopene/OEGCG/chitosan NPs, but not improved by lycopene/PLGA/chitosan NPs. The self-assembled nanostructure of OEGCG combined with lycopene may be a promising application in oral drug delivery in various indications.