Sustained release paclitaxel-loaded core-shell-structured solid lipid microparticles for intraperitoneal chemotherapy of ovarian cancer

Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):957-967. doi: 10.1080/21691401.2019.1576705.

Abstract

The current clinical paradigm for ovarian cancer treatment has a poor prognosis, partially due to the efficacy and toxicity concerns associated with the available chemotherapeutic formulations. To overcome these limitations, we have designed core-shell-structured paclitaxel (PTX) laden solid lipid microparticles (PTX-SLMPs) for intraperitoneal treatment of ovarian cancer. A single-step coaxial electro hydrodynamic atomization (CEHDA) process has been explored to synthesize core-shell structure of PTX-SLMPs with the particle size of 1.76 ± 0.37 µm. Core-shell PTX-SLMPs have high encapsulation efficiency of 94.73% with sustained drug release profile. In vitro evaluation of PTX-SLMPs in SKOV-3 ovarian cancer cells yield significant enhancement in cytotoxicity when compared with Taxol®. In vivo pharmacokinetic study demonstrated slower absorption of PTX into the systemic circulation after intraperitoneal (i.p.) administration of PTX-SLMPs in Wistar rats implying the PTX-SLMPs remained in the peritoneal cavity and released the PTX for prolonged period of time. Through these studies, we have demonstrated the technical potential of core-shell structured PTX-SLMPs, which can enhance passive targeting of PTX to the tumor in the treatment of not only ovarian cancer but also in other peritoneal cancer.

Keywords: Coaxial electro hydrodynamic atomization; core-shell structure; ovarian cancer; paclitaxel; solid lipid microparticles.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Delayed-Action Preparations
  • Drug Carriers / chemistry*
  • Drug Carriers / pharmacokinetics
  • Female
  • Humans
  • Injections, Intraperitoneal
  • Lipids / chemistry*
  • Microspheres*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology*
  • Paclitaxel / administration & dosage
  • Paclitaxel / chemistry*
  • Paclitaxel / pharmacology*
  • Paclitaxel / therapeutic use
  • Particle Size
  • Rats
  • Rats, Wistar
  • Tissue Distribution

Substances

  • Antineoplastic Agents
  • Delayed-Action Preparations
  • Drug Carriers
  • Lipids
  • Paclitaxel