New approaches to tumor therapy with siRNA-decorated and chitosan-modified PLGA nanoparticles

Drug Dev Ind Pharm. 2019 Nov;45(11):1835-1848. doi: 10.1080/03639045.2019.1665061. Epub 2019 Sep 19.

Abstract

Objective: In this study, we aimed to develop a candidate modifited polymeric nanoparticle (NP) system that will kill cancer cells by facilitated to apoptosis and also reduce pain. Significance: The primary goal of treatment, especially for metastatic cancers, is to control the growth of the cancer and to alleviate the symptoms. Pain is one of the commonest symptoms of cancer. In cancer treatment, directing cancer cells to death while simultaneously relieving pain will be a new approach. Methods: Chitosan-modified PLGA NPs were prepared using an nanoprecipitation technique. The NPs were loaded with flurbiprofen and decorated with folic acid. STAT3-siRNA was adsorbed to these polymeric NPs using antisense technology. Results: The NPs were small in size (176.9-220.3 nm) with positive zeta potential (+14.1 mV to +27.2 mV). They had high loading capacity and prolonged release properties over 144 hours. Cytotoxicity studies performed with siRNA showed effective electrostatic interaction due to the positively charged NPs. Folic acid facilitated entry into cancer cells and helped to kill them. Conclusion: The formulation we developed is a potential carrier system for both treatment of cancer and prevention of pain, especially for metastatic cancers.

Keywords: PLGA nanoparticles; STAT3 siRNA; chitosan; flurbiprofen; folic acid.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cancer Pain / etiology
  • Cancer Pain / prevention & control*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chitosan / chemistry
  • Cyclooxygenase Inhibitors / administration & dosage*
  • Cyclooxygenase Inhibitors / pharmacokinetics
  • Drug Carriers / chemistry*
  • Flurbiprofen / administration & dosage*
  • Flurbiprofen / pharmacokinetics
  • Folic Acid / administration & dosage
  • Folic Acid / pharmacokinetics
  • Humans
  • Mice
  • Nanoparticles / chemistry
  • Neoplasms / complications
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Particle Size
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / genetics
  • STAT3 Transcription Factor / antagonists & inhibitors
  • STAT3 Transcription Factor / genetics

Substances

  • Antineoplastic Agents
  • Cyclooxygenase Inhibitors
  • Drug Carriers
  • RNA, Small Interfering
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Flurbiprofen
  • Chitosan
  • Folic Acid