FORMULATION, OPTIMIZATION, AND IN VITRO CHARACTERIZATION OF DASATINIB LOADED POLYMERIC NANOCARRIERS TO EXTEND THE RELEASE OF THE MODEL DRUG

Sandeep Kumar Reddy Adena,Ramoji Kosuru,Kasi Viswanadh Matte

doi:10.22159/ijap.2021v13i5.41995

Abstract

Objective: The present research aims to design, develop, optimize, characterize and evaluate dasatinib (DSB) loaded polymeric nanocarriers to treat chronic myeloid leukaemia (CML) by adopting a quality by design (QbD) approach. Methods: Risk assessment was performed by using failure modes and effects analysis, and optimization of nanoformulation was done by adopting 23 full factorial design. The optimized nanoformulation was characterized by different characterization techniques and evaluated by various in vitro studies. Results: Surface morphology and shape were found to be smooth and spherical. Stability study results revealed that the nanoformulation could be stored in all three storage conditions for safe and long-term use since it retained its pharmaceutical properties. Drug release was 32.06 % in the first 4 h and 79.34 % by the end of 48 h which infers a sustained-release pattern. The hemocompatibility results showed no sign of hemolysis. Cellular uptake study showed approximately 10 to 20-fold much higher intracellular fluorescence intensities of nanoformulation than DSB. Cytotoxicity results confirmed that when compared to the pure drug, the optimized nanoformulation have a potential cytotoxic effect in the treatment of CML since it exhibited a significantly more % growth inhibition. Cell apoptosis assay revealed that the nanoformulation could provide significant antileukaemia activity against K562 cells and further induce K562 cell death with a dose and time-dependent manner. Conclusion: The results of the characterization and evaluation studies showed that the developed nanoformulation offered significant advantages, making it a potential delivery system of DSB for more effective treatment of CML.

Highlights

Dasatinib (DSB) is a novel, potent and multi-targeted inhibitor of BCR-ABL and Src tyrosine kinases activity in the leukaemia cells approved by US FDA (United States Food and Drug Administration) [1, 2]
It indicated the green synthesis of Ch-gold nanoparticles (GNPs), which was confirmed by examining the resultant dispersion UV-Visible spectrophotometry in the scanning range of 300-800 nm
Stabilization and loading of DSB were done after the successful synthesis of Ch-GNPs and DSB was selected as an anticancer drug for loading GNPs to achieve targeted drug delivery

Summary

Introduction

Dasatinib (DSB) is a novel, potent and multi-targeted inhibitor of BCR-ABL and Src tyrosine kinases activity in the leukaemia cells approved by US FDA (United States Food and Drug Administration) [1, 2]. The treatment with DSB is associated with hematological and non-hematological adverse effects [3]. DSB is a biopharmaceutics classification system (BCS) class-II drug, possessing high permeability and low solubility. It has low bioavailability, shorter plasma half-life, lack of specificity, early degradation, rapid elimination, and is recommended in high dose. Shorter plasma half-life, lack of specificity, early degradation, rapid elimination, and is recommended in high dose All these characteristics associated with DSB may be efficiently eradicated by using gold nanoparticles (GNPs) as a drug carrier [5, 6]

Methods

Results

Conclusion