NOVEL VITAMIN D DELIVERY SYSTEM USING PAMAM G5 DENDRIMER: DEVELOPMENT AND CHARACTERIZATION // GP // Dr. Hanan El-Laithy // A.L. Omar Elkady (2018 - 2019)
- GIZA MSA 2019
- 64 P.
- PharmaciesDISTINGUISHED PROJECTS 2019 .
Pharmacy - Organic Chemistry
Osteoporosis is a globally-prevalent progressive skeleton disease among geriatrics, resulting from bone remodeling imbalance and bone resorption. In Egypt, 28.4% of females and 21.9% of males are osteoporotic with brittle, fragile porous and easily- fractured bones. Unfortunately, according to the National Osteoporosis Foundation, there is no cure for osteoporosis, but oral bisphosphonates are frequently-prescribed for the management of the disease under very strict patient dosing guidelines and difficult tolerance of gastroesophageal side effects. Our research aims to develop a novel inhaled Risedronate Sodium (RS) marketed as ActonelŽ in combination with vitamin D using PAMAM G5 dendrimer, with less oral adverse effects and better bioavailability. PAMAM G5-RS- Vitamin D complexes were prepared and characterized for different in vitro aspects [mean size, zeta potential, entrapment efficiency (EE) %, Fourier Transform Infrared spectroscopy (FTIR) and morphological shape by Transmission Electron Microscopy (TEM)]. Preliminary aerodynamic particle size characterization on the developed complex was performed using Anderson Cascade Impactor to determine regional lung deposition. The developed PAMAM inhaled complex was compared in vivo to the oral commercial product ActonelŽ in induced osteoporotic female Wistar albino rats after IP daily injection of dexamethasone phosphate for 2 weeks. The developed complex revealed spherical-shaped nanoparticles with an average size of 180 nm, +0.2 mV zeta potential value which entrapped both drugs successfully. Hydrogen bonding was confirmed by the FTIR spectra between the aliphatic RS OH group as well as Vitamin D alcoholic OH group and PAMAM G5 NH2 group. The HPLC results revealed that most of the nebulized dose got deposited on the collection plate of stage 7 (0.4 - 0.7 micron) of the Anderson Cascade Impactor and the in vivo results inferred that the inhaled complex offered a more efficient therapeutic response than that of the oral one as it promoted bone mineralization and inhibited bone density loss within a short treatment period.
NOVEL VITAMIN D DELIVERY SYSTEM--PAMAM G5 DENDRIMER: DEVELOPMENT