Ormeloxifene nanotherapy for cervical cancer treatment

Int J Nanomedicine. 2019 Sep 3:14:7107-7121. doi: 10.2147/IJN.S200944. eCollection 2019.

Abstract

Background: Cervical cancer (CxCa) ranks as the fourth most prevalent women-related cancer worldwide. Therefore, there is a crucial need to develop newer treatment modalities. Ormeloxifene (ORM) is a non-steroidal, selective estrogen receptor modulator (SERM) that is used as an oral contraceptive in humans. Recent investigations suggest that ORM exhibits potent anti-cancer activity against various types of cancers. Nanoparticulates offer targeted delivery of anti-cancer drugs with minimal toxicity and promise newer approaches for cancer diagnosis and treatment. Therefore, the nanotherapy approach is superior compared to traditional chemotherapy, which is not site-specific and is often associated with various side effects.

Methods: Pursuing this novel nanotherapy approach, our lab has recently developed ORM-loaded poly [lactic-co-glycolic acid] (PLGA), an FDA-approved biodegradable polymer, nanoparticles to achieve targeted drug delivery and improved bioavailability. Our optimized PLGA-ORM nanoformulation showed improved internalization in both dose- and energy-dependent manners, through endocytosis-mediated pathways in both Caski and SiHa cell lines. Additionally, we employed MTS and colony forming assays to determine the short- and long-term effects of PLGA-ORM on these cells.

Results: Our results showed that this formulation demonstrated improved inhibition of cellular proliferation and clonogenic potential compared to free ORM. Furthermore, the PLGA-ORM nanoformulation exhibited superior anti-tumor activities in an orthotopic cervical cancer mouse model than free ORM.

Conclusion: Collectively, our findings suggest that our novel nanoformulation has great potential for repurposing the drug and becoming a novel modality for CxCa management.

Keywords: CxCa; ORM; PLGA; nanoformulation.

MeSH terms

  • Animals
  • Benzopyrans / pharmacology
  • Benzopyrans / therapeutic use*
  • Carcinogenesis / drug effects
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Clone Cells
  • Disease Models, Animal
  • Endocytosis / drug effects
  • Erythrocytes / metabolism
  • Female
  • Hemolysis / drug effects
  • Humans
  • Materials Testing
  • Membrane Potential, Mitochondrial / drug effects
  • Mice, Nude
  • Nanoparticles / therapeutic use*
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
  • Serum / chemistry
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / pathology

Substances

  • Benzopyrans
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • ormeloxifene