Background: Bendamustine HCl, an antineoplastic drug, has a very short life of about 40
minutes which necessitates administration of large doses which leads to increased side effects as well as
Objective: The present work describes the fabrication, optimization, and evaluation of bioactive hydroxyapatite
nanoparticles to achieve sustained delivery of bendamustine HCl.
Methods: Hydroxyapatite nanoparticles (NPs) were prepared by the wet chemical precipitation method
by reacting a calcium and phosphate precursor and the reaction was optimized via Box-Behnken DOE.
The drug was loaded on particles by physical adsorption. Various analytical studies were performed on
the fabricated nanoparticles in addition to biodistribution studies to establish the physicochemical and
biological characteristics of the designed formulation.
Results: pH of the reactant solution was found to have a more profound effect on the particle size and
size distribution in comparison to reactant concentration. The particles were found to have a spherical
morphology by SEM. Size of the blank and drug-loaded nanoparticles was found to be 130±20 nm by
TEM. Energy Dispersive X-ray Spectroscopy (EDS) studies confirmed the presence of hydroxyapatite
as the dominant phase while DSC studies indicated the presence of the drug in its amorphous form after
its adsorption on NPs. Tissue distribution studies further suggested that the majority of drug concentration
was released in blood rather than the other organs implying low organ toxicity.
Conclusion: Bendamustine loaded hydroxyapatite nanoparticles were successfully optimized and fabricated.
Favorable results were obtained in in vitro, in vivo, and analytical studies.