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Tumor-Targeted Delivery of Bufalin-Loaded Modified Albumin-Polymer Hybrid for Enhanced Antitumor Therapy and Attenuated Hemolysis Toxicity and Cardiotoxicity.

Abstract
A novel albumin polymer hybrid with a core-shell structure was designed to target delivery of bufalin, which is an antineoplastic monomer with serious cardiotoxicity. The sheath layer was composed of ursodeoxycholic acid (UA)-modified bovine serum albumin (UA-BSA), while the stable core consisted of poly n-butyl cyanoacrylate (PBCA) nanoparticles. The UA-BSA was synthetized, and the substitution degree was characterized. The physical properties of bufalin-loaded UA-modified protein-PBCA nanocomplexes (BF-uPPNCs), such as morphology, particle size, and encapsulation efficiency, were evaluated. FTIR and DSC revealed the bufalin to be in an amorphous state. Furthermore, the in vitro release study indicated a sustained release profile of BF-uPPNCs. The MTT and cellular uptake study demonstrated that BF-uPPNCs significantly improved the inhibitory effect of the bufalin accompanied with an enhanced cell uptake capacity on HepG2 cells. In addition, in vivo research demonstrated that BF-uPPNCs had a better antitumor effect coupled with improved therapeutic effect, and reduced hemolysis, vascular irritation, and cardiotoxicity. This work therefore presented a novel albumin polymer hybrid with favorable stability, efficient tumor-targeted delivery potential, and side effect reduction ability, which can be a potential vehicle for an anticancer drug.
AuthorsYing Xu, Lei Tang, Peng Chen, Mei Chen, Miaomiao Zheng, Feng Shi, Yanchun Wang
JournalAAPS PharmSciTech (AAPS PharmSciTech) Vol. 22 Issue 4 Pg. 137 (Apr 20 2021) ISSN: 1530-9932 [Electronic] United States
PMID33880681 (Publication Type: Journal Article)
Chemical References
  • Antineoplastic Agents
  • Bufanolides
  • Drug Carriers
  • Polymers
  • Serum Albumin, Bovine
  • bufalin
Topics
  • Animals
  • Antineoplastic Agents (administration & dosage, pharmacology)
  • Bufanolides (administration & dosage, pharmacology)
  • Cardiotoxicity (prevention & control)
  • Cell Death (drug effects)
  • Drug Carriers (chemistry)
  • Hemolysis (drug effects)
  • Hep G2 Cells
  • Humans
  • Nanoparticles (chemistry)
  • Neoplasms (drug therapy)
  • Particle Size
  • Polymers (chemistry)
  • Serum Albumin, Bovine (chemistry)

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