Glycol chitosan in situ coating on PLGA nanoparticle curtails extraneous paclitaxel precipitates and imparts protein corona independent hemocompatibility

Carbohydr Polym. 2020 Jun 1:237:116170. doi: 10.1016/j.carbpol.2020.116170. Epub 2020 Mar 19.

Abstract

Poly (lactide-co-glycolide) (PLGA) nanoparticles surface functionalized with water soluble glycol chitosan (GC) and carboxymethyl chitosan (CMC) has been studied for their drug (Paclitaxel and Doxorubicin) loading, yield, cellular uptake, serum protein adsorption and hemocompatibility. It was observed that Paclitaxel (Ptxl) phase out as Extraneous Ptxl Precipitates (EPP) (>25 %) in case of uncoated and CMC coated low molecular weight (LMW) PLGA nanoparticles (PNPs). The EPP formation was significantly reduced to ∼5 % with GC coating as it enhanced LMW PLGA precipitation and yield predominantly spherical polymeric nanoparticles towards better encapsulation of Ptxl and thus uniform intracellular drug distribution. Interestingly, protein corona analysis showed cmcPNPs and gcPNPs to be distinct from each other in associating mainly with serum proteins of molecular weight < 30 kDa and >30 kDa respectively. While CMC functionalization showed >10 % hemolysis, at similar concentration GC coating was found to provide superior hemocompatibility even in the absence of protein corona.

Keywords: Chitosan; Hemocompatibility; Polymeric nanoparticles; Protein corona; Surface coating.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic* / administration & dosage
  • Antineoplastic Agents, Phytogenic* / chemistry
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chemical Precipitation
  • Chitosan* / administration & dosage
  • Chitosan* / chemistry
  • Drug Liberation
  • Erythrocytes / drug effects
  • Goats
  • Humans
  • Nanoparticles* / administration & dosage
  • Nanoparticles* / chemistry
  • Paclitaxel* / administration & dosage
  • Paclitaxel* / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer* / administration & dosage
  • Polylactic Acid-Polyglycolic Acid Copolymer* / chemistry
  • Protein Corona
  • Rats

Substances

  • Antineoplastic Agents, Phytogenic
  • Protein Corona
  • glycol-chitosan
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Chitosan
  • Paclitaxel