Clinicopathological and immunohistochemical evaluation of lonidamine-entrapped lipid-polymer hybrid nanoparticles in treatment of benign prostatic hyperplasia: An experimental rat model

ŞENGEL TÜRK C. T., ALÇIĞIR M. E., EKİM O., BAKAR ATEŞ F., HASÇİÇEK C.

EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, vol.157, pp.211-220, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 157
  • Publication Date: 2020
  • Doi Number: 10.1016/j.ejpb.2020.10.016
  • Journal Name: EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.211-220
  • Keywords: Lipid-polymer hybrid nanoparticles, Benign prostatic hyperplasia, Lonidamine, Local treatment, Hepatic toxicity, CANCER, EXTRACT, IMPROVE, ANTIGEN, CELLS, OPTIMIZATION, METABOLISM, CASTRATION, EXPRESSION, INDUCTION
  • Ankara University Affiliated: Yes

Abstract

Benign prostatic hyperplasia (BPH) is a progressive proliferative disease, the incidence of which is constantly increasing due to aging of population. In this research, a hexokinase-II enzyme inhibiting agent, lonidamine - the use of which is limited in BPH treatment due to high hepatic toxicity observed after three months of treatment - was selected as an active agent, based on its mechanism of action in treating BPH. The aim of this study was to evaluate in vivo therapeutic efficacy and hepatic toxicity of lipid-polymer hybrid nanoparticles of lonidamine in a rat BPH model created in rat prostates. After local injections of hybrid nanoparticles of lonidamine were administered to the rat prostates, hyperplasic structures of prostates were evaluated in terms of prostatic index values, immunohistochemical evaluations, and histopathological findings. Liver blood enzyme values were also determined to specify hepatic toxicity. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) reaction and histopathological methods to determine intravital degenerative destruction in liver. Through this study, lonidamine-loaded hybrid nanoparticles were found to reduce the he-patic toxicity and increase therapeutic efficiency of lonidamine. Therefore, lonidamine-entrapped hybrid nanoparticles may provide a promising, and very safe, drug delivery strategy in the treatment of BPH.