Title : All-trans retinoic acid loaded chitosan lipid nanocomplex for enhancing its diabetic nephropathy healing effect
Abstract:
The present study aims to formulate all-trans retinoic acid (ATRA) loaded chitosan lipid nanocomplex (CHLNC) for enhancing its solubility and oral delivery. This is to improve ATRA therapeutic effect on diabetic nephropathy (DN). CHLNC was prepared by o/w homogenization, employing stearic acid, to form lipid nanoparticles coated with chitosan that is stabilized against acidic pH through sodium tripolyphosphate (TPP) crosslinking. Chitosan coated (F7) and naked lipid nanoparticles (F6) were also prepared for comparison with CHLNC. In vitro characterization for the prepared formulations were 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 CHLNC was more stable than F7. In vitro release indicated an enhanced release of ATRA. In vitro mucoadhesion study proved a notable mucoadhesive property for CHLNC. In DN rat model, serum levels of creatinine and urea were elevated. 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 and urea levels as well as elevating AMPK and LKB1 levels. The order of activity was: CHLNC > F7 > F6 > free ATRA. This study revealed the positive impacts of crosslinking of chitosan coat with TPP to avoid solubility and hence detachment of the coat in the gastric acidic pH. Thus, CHLNC can be delivered intact to intestine, unlike F7, and make benefit of mucoadhesive properties of chitosan regarding enhancement of oral absorption of the loaded ATRA.
