SN-38 loading capacity of hydrophobic polymer blend nanoparticles: formulation, optimization and efficacy evaluation

Drug Dev Ind Pharm. 2017 Mar;43(3):502-510. doi: 10.1080/03639045.2016.1268151. Epub 2016 Dec 20.


One of the most important problems in nanoencapsulation of extremely hydrophobic drugs is poor drug loading due to rapid drug crystallization outside the polymer core. The effort to use nanoprecipitation, as a simple one-step procedure with good reproducibility and FDA approved polymers like Poly(lactic-co-glycolic acid) (PLGA) and Polycaprolactone (PCL), will only potentiate this issue. Considering that drug loading is one of the key defining characteristics, in this study we attempted to examine whether the nanoparticle (NP) core composed of two hydrophobic polymers will provide increased drug loading for 7-Ethyl-10-hydroxy-camptothecin (SN-38), relative to NPs prepared using individual polymers. D-optimal design was applied to optimize PLGA/PCL ratio in the polymer blend and the mode of addition of the amphiphilic copolymer Lutrol®F127 in order to maximize SN-38 loading and obtain NPs with acceptable size for passive tumor targeting. Drug/polymer and polymer/polymer interaction analysis pointed to high degree of compatibility and miscibility among both hydrophobic polymers, providing core configuration with higher drug loading capacity. Toxicity studies outlined the biocompatibility of the blank NPs. Increased in vitro efficacy of drug-loaded NPs compared to the free drug was confirmed by growth inhibition studies using SW-480 cell line. Additionally, the optimized NP formulation showed very promising blood circulation profile with elimination half-time of 7.4 h.

Keywords: 7-Ethyl-10-hydroxy-camptothecin (SN-38); D-optimal design; PLGA/PCL/PEO–PPO–PEO blend; Polymeric nanoparticles; nanoprecipitation; solid tumors.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / chemistry*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives*
  • Camptothecin / chemistry
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Compounding
  • Drug Evaluation, Preclinical / methods
  • Female
  • Humans
  • Hydrophobic and Hydrophilic Interactions*
  • Irinotecan
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry*
  • Particle Size
  • Polymers / administration & dosage
  • Polymers / chemistry*
  • Rats
  • Rats, Wistar
  • Treatment Outcome


  • Antineoplastic Agents, Phytogenic
  • Polymers
  • Irinotecan
  • Camptothecin