Preparation, Characterization, and Evaluation of Cisplatin-Loaded Polybutylcyanoacrylate Nanoparticles with Improved In Vitro and In Vivo Anticancer Activities.

Mohsen Ghaferi,Hasan Ebrahimi Shahmabadi,Aun Raza,Samar Amari,Bhalchandra Vivek Mohrir,Seyed Ebrahim Alavi

doi:10.3390/ph13030044

Abstract

This study aimed to evaluate the therapeutic efficacy of the cisplatin encapsulated into polybutylcyanoacrylate (PBCA) nanoparticles for the treatment of kidney cancer. The nanoformulation was successfully developed using the miniemulsion polymerization method and characterized in terms of size, size distribution, drug loading and encapsulation efficiencies, drug release behavior, in vitro cytotoxicity effects, in vivo toxicity, and therapeutic effects. Cisplatin-loaded PBCA nanoparticles were confirmed to be in nanoscale with the drug entrapment efficiency of 23% and controlled drug release profile, in which only 9% of the loaded drug was released after 48 h. The nanoparticles caused an increase in the cytotoxicity effects of cisplatin against renal cell adenocarcinoma cells (ACHN) (2.3-fold) and considerably decreased blood urea nitrogen and creatinine concentrations when compared to the standard cisplatin (1.6-fold and 1.5-fold, respectively). The nanoformulation also caused an increase in the therapeutic effects of cisplatin by 1.8-fold, in which a reduction in the mean tumor size was seen (3.5 mm vs. 6.5 mm) when compared to the standard cisplatin receiver rats. Overall, cisplatin-loaded PBCA nanoparticles can be considered as a promising drug candidate for the treatment of kidney cancer due to its potency to reduce the side effects of cisplatin and its toxicity and therapeutic effects on cancer-bearing Wistar rats.

Highlights

Renal cell carcinoma (RCC; known as renal adenocarcinoma), with increasing incidence, causes 90% of renal malignancies [1] and is responsible to 2.2% of all malignancies [2]
In cancer therapy, various studies have shown that PBCA nanoparticles are excellent carrier colloids for chemotherapeutic agents as they enhance the therapeutic effects of chemotherapeutics and reduce their side effects [9,26,27,28,29]
This study shows that nanoparticles had a slow and controlled release of cisplatin, and for this reason, this nanoformulation was potent enough to enhance the cytotoxicity effects of cisplatin (2.3-fold) compared to the standard cisplatin

Summary

Introduction

Renal cell carcinoma (RCC; known as renal adenocarcinoma), with increasing incidence, causes 90% of renal malignancies [1] and is responsible to 2.2% of all malignancies [2]. RCC is a highly metastasis malignancy [3] that 25–30% of RCC patients are diagnosed with metastasis [1] It is one of the most lethal cancers with a five-year survival rate of 15–25% [4]. Cisplatin plays a vital role in cancer treatment and has been widely used to treat various types of cancers, including ovarian, cervical, head and neck, and non-small-cell lung cancer for years [7]. It forms a cisplatin-DNA adduct, which causes cell death through the cell apoptotic process [8]. Nanoparticles are considered as a promising approach for improving the pharmacokinetics of various types of drugs [10,11]

Objectives

Results

Conclusion