Planta Med 2015; 81 - PW_131
DOI: 10.1055/s-0035-1565755

Withania somnifera leaf extract delivery as a nanoparticle protect the glioma cells from oxidative damage

G Marslin 1, G Franklin 1, B Sarmento 2, 3, AC Dias 1
  • 1Centre for the Research and Technology of Agro-Environment and Biological Sciences (CITAB-UM), AgroBioPlant Group, Department of Biology, University of Minho, Portugal, Braga, Portugal
  • 2CESPU, IINFACTS – Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto Superior de Ciências da Saúde-Norte, Gandra-PRD, Portugal, Gandra, Portugal
  • 3INEB – Instituto de Engenharia Biomédica, University of Porto, Porto, Portugal, Porto, Portugal

Withania somnifera (L) is a medicinal plant used to treat stress and neurological disorders. Withanolides are the major compounds responsible for pharmacological activities of this species. Some issues like poor water solubility, poor permeability and bioavailability restricts their therapeutic efficacy. To overcome this, some approaches have been envisaged like nanoparticle drug delivery.

In this work, we have developed and characterized a Withania somnifera leaf Extract (WSE) encapsulated in PCL and MPEG-PCL nanoparticles, prepared by solvent displacement method. HPLC-DAD analysis was performed and confirmed the presence of similar bioactive compounds in WSE and in the nanoparticles formed: withanolide-A, withanolide-B, withaferin-A, and 12-deoxy-withastramonolide. The MPEG-PCL nanoformulation showed higher entrapment efficacy (73%) than PCL nanoparticles (59%). Nanoparticles were physically characterised by laser doppler anemometry, transmission electron microscopy and X-Ray diffraction. The results confirmed that size of PCL-WSE and MPEG-PCL-WSE range between 210 – 240nm and 30 – 70nm, respectively, being in spherical shape.

In vitro release behavior of WSE loaded PCL and MPEG-PCL nanoparticles showed features of a controlled release pattern. Cellular studies with U251 glioma cells exhibited a high cellular uptake of WSE-PCL and namely WSE-MPEG-PCL nanoparticles.

WSE, WSE-PCL and WSE-MPEG-PCL nanoparticles significantly protected neuronal cells (U251) against oxidative damage induced by t-BHP. Moreover, both WSE- PCL and WSE-MPEG-PCL nanoparticles showed better protective effect then free WSE. WSE-MPEG-PCL nanoparticles showed the highest neuroprotection effect (95% for 10 µg/mL, EC50 1 µg/mL). Together, our results indicated that MPEG-PCL-WSE might be an efficient way for WSE brain delivery.

Acknowledgement: Fundação para a Ciência e Tecnologia (FCT) projects PTDC/AGR-ALI/105169/2008 and PEst-OE/AGR/UI4033/2014 and PhD fellowship (SFRH/BD/72809/2010) are acknowledged.