Zapped assembly of polymeric (ZAP) nanoparticles for anti-cancer drug delivery

Nanoscale. 2019 Jan 23;11(4):1847-1855. doi: 10.1039/c8nr09944h.

Abstract

The starting hypothesis for this work was that microwave synthesis could enable the rapid assembly of polymers into size-specific nanoparticles (NPs). The Zapped Assembly of Polymeric (ZAP) NPs was initially realized using poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) block copolymers and distinct microwave reaction parameters. A library of polymeric NPs was generated with sizes ranging from sub-20 nm to 350 nm and low polydispersity. Select ZAP NPs were synthesized in 30 seconds at different scales and concentrations, up to 200 mg and 100 mg mL-1, without substantial size variation. ZAP NPs with diameters of 25 nm, 50 nm, and 100 nm were loaded with the chemotherapeutic paclitaxel (PXL), demonstrated unique release profiles, and exhibited dose-dependent cytotoxicity similar to Taxol. Incorporation of d-alpha tocopheryl polyethylene glycol succinate (TPGS) and PLGA33k allowed for the production of a sub-40 nm NP with an exceptionally high loading of PXL (12.6 wt%, ca. 7 times the original NP) and a slower release profile. This ZAP NP platform demonstrated scalable, flexible, and tunable synthesis with potential toward clinical scale production of size-specific drug carriers.

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry*
  • Antineoplastic Agents, Phytogenic / metabolism
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Cell Survival / drug effects
  • Drug Carriers / chemistry*
  • Drug Liberation
  • HeLa Cells
  • Humans
  • Microwaves
  • Nanoparticles / chemistry*
  • Paclitaxel / chemistry
  • Paclitaxel / pharmacology
  • Particle Size
  • Polyesters / chemistry*
  • Polyethylene Glycols / chemistry*

Substances

  • Antineoplastic Agents, Phytogenic
  • Drug Carriers
  • Polyesters
  • polyethylene glycol-poly(lactide-co-glycolide)
  • Polyethylene Glycols
  • Paclitaxel