Carfilzomib and paclitaxel co-loaded protein nanoparticles an effective therapy against pancreatic adenocarcinomas

Wen Ting Cheng, Hsiu O. Ho, Shyr Yi Lin, Der Zen Liu, Ling Chun Chen, Ming Thau Sheu

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Therapeutic efficacy of pancreatic adenocarcinomas (PACs) with combined therapy of carfilzomib (CFZ) and paclitaxel (PTX) co-loaded in human serum albumin (HSA) nanoparticles (NPs) was examined. Methods: CFZ and PTX were encapsulated individually or combined into HSA NPs by a simple reverse self-assembly method developed to achieve an optimal combination ratio for synergistic therapy. CFZ or/and PTX loaded HSA nanoparticles were physically characterized and the evaluation of combination index, drug release, pharmacokinetic, anti-tumor, and biodistribution studies were conducted. Results: All resultant drug-loaded HSA NPs were spherical with a particle size of <150 nm and a zeta potential of −21.1~−23.0 mV. Drug loading rates and entrapment efficiencies were 9.1%~10.1% and 90.7%~97.1%, respectively. CFZ and PTX demonstrated synergistic effects in an MIA PaCa-2 cytotoxicity at a 1:2 ratio (CI50 were 0.01~0.25). In vitro dissolution revealed that the CFZ/PTX ratio released from the co-loaded HSA NPs (CFZ/PTX/HSA NPs) was about 1.77~2.08, which conformed to the designated loaded ratio. In vivo evaluation showed that the combined therapy of CFZ and PTX at a 1:2 ratio co-loaded in HSA NPs (CFZ/PTX/HSA NPs) demonstrated optimal synergistic improvement of the growth inhibi-tion of MIA PaCa-2 cells with less systematic toxicity, even though the pharmacokinetic profiles observed did not show obvious beneficial and their biodistributions in tumors were found to be smaller. Conclusion: The one-pot reverse assembly method developed was environmentally friendly and capable of co-loading an optimal combination ratio of two chemodrugs into HSA NPs for synergistic therapy.

Original languageEnglish
Pages (from-to)6825-6841
Number of pages17
JournalInternational Journal of Nanomedicine
Volume16
DOIs
Publication statusPublished - Oct 2021

Keywords

  • Carfilzomib
  • Co-loading
  • Human serum albumin
  • Nanoparticles
  • Paclitaxel
  • Synergism

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry

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