Modification of polyethylene glycol onto solid lipid nanoparticles encapsulating a novel chemotherapeutic agent (PK-L4) to enhance solubility for injection delivery

Int J Nanomedicine. 2012;7:4995-5005. doi: 10.2147/IJN.S34301. Epub 2012 Sep 17.


Background: The synthetic potential chemotherapeutic agent 3-Chloro-4-[(4-methoxyphenyl) amino]furo[2,3-b]quinoline (PK-L4) is an analog of amsacrine. The half-life of PK-L4 is longer than that of amsacrine; however, PK-L4 is difficult to dissolve in aqueous media, which is problematic for administration by intravenous injection.

Aims: To utilize solid lipid nanoparticles (SLNs) modified with polyethylene glycol (PEG) to improve the delivery of PK-L4 and investigate its biodistribution behavior after intravenous administration.

Results: The particle size of the PK-L4-loaded SLNs was 47.3 nm and the size of the PEGylated form was smaller, at 28 nm. The entrapment efficiency (EE%) of PK-L4 in SLNs with and without PEG showed a high capacity of approximately 100% encapsulation. Results also showed that the amount of PK-L4 released over a prolonged period from SLNs both with and without PEG was comparable to the non-formulated group, with 16.48% and 30.04%, respectively, of the drug being released, which fit a zero-order equation. The half-maximal inhibitory concentration values of PK-L4-loaded SLNs with and those without PEG were significantly reduced by 45%-64% in the human lung carcinoma cell line (A549), 99% in the human breast adenocarcinoma cell line with estrogen receptor (MCF7), and 95% in the human breast adenocarcinoma cell line (MDA-MB-231). The amount of PK-L4 released by SLNs with PEG was significantly higher than that from the PK-L4 solution (P < 0.05). After intravenous bolus of the PK-L4-loaded SLNs with PEG, there was a marked significant difference in half-life alpha (0.136 ± 0.046 hours) when compared with the PK-L4 solution (0.078 ± 0.023 hours); also the area under the curve from zero to infinity did not change in plasma when compared to the PK-L4 solution. This demonstrated that PK-L4-loaded SLNs were rapidly distributed from central areas to tissues and exhibited higher accumulation in specific organs. The highest deposition of PK-L4-loaded SLNs with PEG was found in the lung and spine.

Conclusion: Sufficient amounts of PK-L4 were entrapped in the SLNs, and the pharmacokinetic behavior of PK-L4-loaded SLNs was established. This formulation successfully resolved the delivery problem, and the drug was localized in particular organs.

Keywords: 3-b]quinoline; 3-chloro-4-[(4-methoxyphenyl)amino]furo[2; SLNs; biodistribution; cytotoxicity; solubility.

MeSH terms

  • Amsacrine / administration & dosage*
  • Amsacrine / analogs & derivatives
  • Amsacrine / pharmacokinetics*
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Injections, Intravenous
  • Lipids / chemistry*
  • Male
  • Metabolic Clearance Rate
  • Nanocapsules / administration & dosage
  • Nanocapsules / chemistry*
  • Organ Specificity
  • Polyethylene Glycols / chemistry*
  • Rats
  • Rats, Wistar
  • Solubility
  • Tissue Distribution


  • Antineoplastic Agents
  • Lipids
  • Nanocapsules
  • Amsacrine
  • Polyethylene Glycols