ABSTRACT

Carfilzomib, a recently FDA-approved proteasome inhibitor, has remarkable anti-myeloma (MM) activity. However, its effectiveness is limited by associated severe side-effects, short circulation half-life, and limited solubility. Here, we report the engineering of liposomal carfilzomib nanoparticles to overcome these problems and enhance the therapeutic efficacy of carfilzomib by increasing tumoral drug accumulation while decreasing systemic toxicity. As an effort to formulate more efficient carfilzomib NPs for systemic administration, this research work is an endeavour to optmize the amount of polymer/ stabilizer, concentration of stabilizer and amount of carfilzomib required to get the ideal NPs using three different biodegradable and biocompatible polymers. The ideal particle size, PCL, PLGA and PLA NPs were prepared and selected for the in-vitro and in-vivo study. PLGA carfilzomib nanoparticles were efficiently taken up by MM cells, demonstrated proteasome inhibition, induced apoptosis, and exhibited enhanced cytotoxicity against MM cells. Based on the results it was observed that quality NPs with 100 % EE, high DC and % recovery were obtained using,20 mg of PCL (PCL/F68/05), 100 mg of PLGA (PLGA/F68/09) and 50 mg of PLA (PLA/F68/07) with 0.5 % PF 68 as stabilizer. The reason for high EE in case of the prepared PNPs may be due to low aqueous solubility of carfilzomib, fast rate of precipitation of polymer during preparation and selection of polymer solvent with high vapour pressure and the low viscosity of the internal phase. The prepared PNPs were characterized for their shape and structure using SEM, TEM and AFM. Taken together, this study establishes the successful synthesis of liposomal carfilzomib nanoparticles that demonstrate improved therapeutic index and the potential to improve patient outcome in MM. Keywords: Carfilzomib, PLGA, Scanning Electron Microscopy
Publication date: 25/09/2021

https://ijbpas.com/pdf/2021/September/MS_IJBPAS_2021_SEPT_SPCL_1022.pdf

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https://doi.org/10.31032/IJBPAS/2021/10.9.1022