Abstract

Uncaria tomentosa (UT) extracts have been shown to have promising anti-tumor activity. We hypothesized that its incorporation into nanostructured systems could improve the anticancer properties. Here, poly-e-caprolactone (PCL) and poly-d,l-lactide-co-glycolide (PLGA) were employed to generate nanoparticles loaded with UT extract in a single emulsion solvent evaporation method. The nanoparticles were characterized by particle size, zeta potential, morphology and entrapment efficiency along with stability and release profiles. The nanoparticles presented entrapment efficiencies above 60% and a mean diameter below 300nm. UT-PCL nanoparticles presented higher entrapment efficiency and mean particle size as well as a slow release rate. The UT-PLGA nanoparticles showed higher drug loading. Two prostate cancer cell-lines, LNCaP and DU145 that were derived from metastatic sites, served as model systems to assess cytotoxicity and anti-cancer activity. In vitro, both formulations reduced the viability of DU145 and LNCaP cells. Yet, the UT-PLGA nanoparticles showed higher cytotoxicity towards DU145 cells while the UTPCL against LNCaP cells. The results confirm that the incorporation of UT into nanoparticles could enhance its anti-cancer activities that can offer a viable alternative for the treatment of prostrate canner and highlights the potential of nanostructured systems to provide a promising methodology to enhance the activity of natural extracts.

Highlights

  • Uncaria tomentosa (UT) is a vine plant found in the Peruvian Amazon, commonly known as “cat’s claw”, whose bark has been known to be used in a variety of popular therapeutic preparations (Heitzman et al 2005)

  • No significant differences were observed in the polydispersity index and both presented as spherical shapes in the morphological analysis (Figure 2), with mean diameters measured by TEM consistent with the dynamic light scattering (DLS) measurements

  • We evaluated the cellular response of two human prostate cancer (PC) cell lines (LNCaP and DU145) following treatment with UT samples diluted in culture medium (Np UT-PCL, Np UT-PLGA, Np PCL, Np PLGA or UT control solution (UT Sol), polyvinyl alcohol (PVA) Sol, Lutrol Sol)

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Summary

Introduction

Uncaria tomentosa (UT) is a vine plant found in the Peruvian Amazon, commonly known as “cat’s claw”, whose bark has been known to be used in a variety of popular therapeutic preparations (Heitzman et al 2005). Different UT extracts have been reported to have in vitro effects on a wide range of cancer cell lines (Fazio et al 2008, Pilarski et al 2010). A number of studies have further indicated that plant extracts display promising anti-cancer activities (Pilarski et al 2010, Dreifuss et al 2010, Miranda & Freitas 2008). The results from a clinical trial conducted by Araújo et al (2012) suggested that a dried hydroalcoholic extract of UT could be considered an effective adjuvant treatment to breast cancer based on a reduction in the neutropenia caused by chemotherapy and a protective effect for DNA. The anti-tumor activity of UT extract has been mainly attributed to the presence of pentacyclic oxindole alkaloids (POAs; Figure 1), principally as mitraphylline (Giménez et al 2010, An Acad Bras Cienc (2020) 92(1)

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