tretinoin and triphosphoric-acid

The present study aims to formulate all-trans retinoic acid (ATRA) loaded chitosan/tripolyphosphate lipid hybrid nanoparticles (CTLHNs) for enhancing its solubility and oral delivery. This is to improve ATRA therapeutic effect on diabetic nephropathy (DN). CTLHNs were prepared by o/w homogenization, employing stearic acid, to form lipid nanoparticles coated with chitosan that is stabilized against acidic pH via sodium tripolyphosphate crosslinking. Chitosan coated (F7) and naked lipid nanoparticles (F6) were also prepared for comparison with CTLHNs. In vitro characterization for the prepared formulations was performed comprising entrapment efficiency, particle size, zeta potential, transmission electron microscopy, FT-IR spectroscopy and x-ray diffraction. Stability of chitosan coat in GI fluid revealed that CTLHNs were more stable than F7. In vitro release indicated an enhanced release of ATRA from the developed formulations. In vitro mucoadhesion study proved a notable mucoadhesive property for CTLHNs. In DN rat model, serum levels of creatinine and urea were elevated, over expression of tumor necrosis factor alpha (TNF-α), granulocyte macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1) were observed. In addition, adenosine monophosphate activated protein kinase (AMPK) and liver kinase B1 (LKB1) expressions were decreased in DN rats. Treatment with free ATRA and the selected formulations led to a significant amelioration of DN by reducing of creatinine, urea, TNF-α, ICAM-1, GM-CSF, VEGF levels as well as elevating AMPK and LKB1 levels. The order of activity was: CTLHNs > F7 > F6 > free ATRA, as proved by histopathological examination.

Topics: Animals; Chitosan; Diabetes Mellitus; Diabetic Nephropathies; Drug Carriers; Lipids; Nanoparticles; Particle Size; Polyphosphates; Rats; Spectroscopy, Fourier Transform Infrared; Tretinoin; Vascular Endothelial Growth Factor A

In this paper, it is demonstrated that all-trans, 9-cis and 13-cis retinoic acid (RA) decreased the sensitivity of SK-N-BE(2)c neuroblastoma cells towards the chemotherapeutic agent cyclopentenyl cytosine (CPEC), a potent inhibitor of cytosine-5'-triphosphate synthetase. Retinoic acid attenuated CPEC-induced apoptosis as reflected by a decreased caspase-3 induction. Retinoic acid decreased the accumulation of CPEC, whereas the salvage of cytidine was strongly increased. Metabolic labeling studies using [(3)H]uridine showed a strongly decreased biosynthesis of CTP via CTP synthetase. Retinoic acid likely confers resistance of neuroblastoma cells to CPEC in part by slowing down proliferation, and in part by shifting the synthesis of CTP towards the salvage of cytidine, thereby bypassing CTP synthetase.

Topics: Antineoplastic Agents; Apoptosis; Cell Differentiation; Cell Division; Cytidine; Cytidine Triphosphate; Drug Interactions; Humans; Neuroblastoma; Polyphosphates; Tretinoin; Tumor Cells, Cultured