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 Actonel® 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 Actonel® 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.