A novel self-assembled nanoparticle platform based on pectin-eight-arm polyethylene glycol-drug conjugates for co-delivery of anticancer drugs

Mater Sci Eng C Mater Biol Appl. 2018 May 1:86:28-41. doi: 10.1016/j.msec.2017.12.018. Epub 2017 Dec 16.

Abstract

The application of non-toxic carriers to increase drug loading, multi-drug delivery, and extremely small size of nano-drugs to construct a tremendous transmission system is the goal for all researchers to be pursued. The proposal of natural pectin nano-platform for delivery of multiple drugs is critical for biomedical research, especially a particle size of below 100nm with high yield. Here we design a new core-shell structure pectin-eight-arm polyethylene glycol-ursolic acid/hydrooxycampothecin nanoparticle (Pec-8PUH NPs) through a special self-assembly method for stabilizing and dispersing particles, improving water-solubility, and achieving drug controlled release. The obtained Pec-8PUH NPs possessed appropriate size (~91nm), drug-loaded efficiency and encapsulation efficiency through the regulation of eight-arm polyethylene glycol. In addition, Pec-8PUH NPs could enhance cell cytotoxicity, shorten blood retention time (7.3-fold UA, 7.2-fold HCPT) and more effective cellular uptake than free drugs, which exhibited an obvious synergistic effect of UA and HCPT by the co-delivery. 4T1 tumor-bearing mice also showed a higher survival rate than free UA and free HCPT. The result further shows that this novel drug delivery system has a promising potential for anti-cancer combination therapy.

Keywords: Co-delivery; Conjugate; Nanoparticle; Pectin; Self-assemble.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / therapeutic use
  • Camptothecin / analogs & derivatives
  • Camptothecin / chemistry
  • Camptothecin / metabolism
  • Camptothecin / therapeutic use
  • Cell Line, Tumor
  • Cell Survival
  • Drug Carriers / chemistry*
  • Drug Carriers / toxicity
  • Drug Liberation
  • Female
  • Half-Life
  • Hemolysis / drug effects
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry*
  • Nanoparticles / toxicity
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Particle Size
  • Pectins / chemistry*
  • Polyethylene Glycols / chemistry*
  • Transplantation, Heterologous
  • Triterpenes / chemistry
  • Triterpenes / metabolism
  • Ursolic Acid

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Triterpenes
  • hydroxycamptothecinum
  • Polyethylene Glycols
  • Pectins
  • Camptothecin