Galactosylated Albumin nanoparticles bearing Cimetidine for effective management of Acetaminophen induced hepatotoxicity

In the present study, an attempt was made to develop galactosylated albumin nanoparticles of Cimetidine for treatment of Acetaminophen induced hepatotoxicity. By developing the galactosylated nanoparticulated delivery of Cimetidine the required action of drug at the target site i.e at liver can be provided. The advantage of targeting helps to reduce the systemic side effects which may be occur due to the distribution of the drug to the other organs and thus helps in maintain  the  required concentration of drug at the desired site. The use of cimetidine to treat Acetaminophen induced hepatotoxicity was based on the observation that it would lead to the competitive inhibition of the enzyme  CYP ۴۵۰ ۲E۱ and reduce the acetaminophen metabolism to  N-acetyl-p-benzoquinoneimine (NAPQI), a highly reactive, electrophilic molecule .Thus, it might be useful in treatment of Acetaminophen induced hepatotoxicity. The galactosylated albumin nanoparticles were prepared for the selective delivery of an, Cimetidine to the asialoglycoprotein receptor (ASGP-R) which is particularly presents on mammilla in hepatocytes. The albumin nanoparticles (NPs) were prepared by using desolvation method and efficiently conjugated with galactose. Various parameters such as particle size, % entrapment efficiency and drug loading efficiency, percentage yield, in vitro drug release, were determined. The size of nanoparticles (both plain and coated NPs) was found to be in range of ۲۰۰-۲۵۰ nm, and maximum drug payload was found to be ۱۹.۰۸% ± ۱.۱۰ .The maximum drug content was found to be ۳۰.۸۰% ± ۰.۳ and ۲۷.۰۹% ± ۰.۵ respectively in plain and galactose coated nanoparticles while the maximum entrapment efficiency was found to be ۹۰.۶۸% ± ۰.۵ and ۹۱.۷۵% ± ۰.۵۹ in plain and coated nanoparticles. It was also found that coating of nanoparticles increases the size of nanoparticles.

Keywords:

Hepatotoxicity , Galactose , Cimetidine , Targeting , Asialoglycoprotein receptor