Optimized mucus adhesion and penetration of lipid-polymer nanoparticles enables effective nose-to-brain delivery of perillyl alcohol for glioblastoma therapy.

in Drug delivery and translational research by Edilson Ribeiro de Oliveira Junior, Jonathan Matheus Silva, Mariana Arraes Salomão, Nathalia Correa de Almeida Oliveira, Carla Santos de Freitas, Natália Noronha Ferreira, Natalia Sanchez Moreno, Camila Fernanda Rodero, Daniel Graziani, Valtencir Zucolotto, Sebastião Antônio Mendanha, Eliana Martins Lima

TLDR

  • Scientists developed nanoparticles that can deliver a drug directly to the brain through the nose, improving treatment for glioblastoma brain cancer.
  • The nanoparticles combine mucoadhesiveness and mucus penetration properties to enhance mucosal retention and effective mucus diffusivity.
  • The study results show improved delivery of the drug to the brain, with potential for effective glioblastoma therapy.

Abstract

The delivery of drugs directly from the nose to the brain has been explored for the treatment of neurological diseases, such as glioblastoma, by overcoming the blood-brain barrier. Nanocarriers have demonstrated outstanding ability to enhance drug bioavailability in the brain, following intranasal administration. However, the performance of these nanosystems may be hindered by inadequate interactions with the nasal mucosa, limiting their effectiveness in reaching the olfactory region, and consequently, the translocation of particles to the brain. Here, we designed hybrid lipid-polymer nanoparticles (LPNP), containing the cationic lipid DOTAP and the triblock copolymer PluronicF127 to combine the mucoadhesiveness and mucus-penetrating properties. Perillyl alcohol (POH), a molecule currently under clinical trials against glioblastoma, via intranasal route, was entrapped in the nanoparticles. LPNP-POH exhibited a balanced profile of mucus adhesion and penetration, suggesting that the formulation may enhance mucosal retention while maintaining effective mucus diffusivity. In vivo evaluations displayed higher translocation of LPNP-POH from the nasal cavity to the brain. LPNP-POH resulted in a 2.5-fold increase in the concentration of perillyl acid (a primary metabolite of POH) in the cerebral tissue compared to the free drug. In vitro assays demonstrated that LPNP-POH increased the cytotoxicity and reduced the tumor growth of U87MG glioma cells. These results highlighted that the engineered formulation, with optimized mucoadhesiveness and mucus penetration properties, improved nose-to-brain delivery of POH, offering a promising potential for glioblastoma therapy.

Overview

  • The study explores the development of nanocarriers for the delivery of drugs directly from the nose to the brain, specifically for the treatment of glioblastoma.
  • The researchers designed hybrid lipid-polymer nanoparticles (LPNP) containing cationic lipid DOTAP and triblock copolymer PluronicF127 to enhance drug bioavailability and interaction with the nasal mucosa.
  • The study aimed to investigate the potential of LPNP in delivering perillyl alcohol (POH) to the brain and its efficacy in treating glioblastoma.

Comparative Analysis & Findings

  • The study found that LPNP-POH exhibited a balanced profile of mucus adhesion and penetration, suggesting improved mucosal retention and effective mucus diffusivity.
  • In vivo evaluations showed higher translocation of LPNP-POH from the nasal cavity to the brain compared to free drug.
  • LPNP-POH resulted in a 2.5-fold increase in the concentration of perillyl acid in cerebral tissue compared to free drug, indicating improved delivery of POH to the brain.

Implications and Future Directions

  • The study highlights the potential of LPNP-POH as a promising therapeutic approach for glioblastoma treatment.
  • The optimized mucoadhesiveness and mucus penetration properties of LPNP-POH may improve nose-to-brain delivery of POH.
  • Future studies may investigate the potential of LPNP-POH in treating other neurological disorders and explore the mechanisms underlying the improved delivery and efficacy of POH.
Read Full Article