Effective Delivery of Phytosterol Based Drugs Against Colon Cancer

Abstract

newline Background: Nanoparticle-based drug delivery systems are gaining much attention for the treatment newlineof various diseases. Over the past decades, extraordinary advances have been made successfully on newlinethe development of novel drug delivery systems for encapsulation of plant active metabolites newlineincluding organic, inorganic and hybrid nanoparticles. The advanced formulas are confirmed to have newlineextraordinary benefits over conventional and previously used systems in the manner of solubility, newlinebioavailability, toxicity, pharmacological activity, stability, distribution, sustained delivery, and both newlinephysical and chemical degradation. In this backdrop, the present work was carried out to evaluate the newlinein vivo anti-colon cancer activity of Hydroxyapetite alginate loaded Lawsonia inermis methanolic newlineextract containing and#946;-Sitosterol nanocomposites, and in vitro anticancer activity of Lawsonia inermis newlineand#946;-Sitosterol imbedded gold nanocomposites for colon cancer. newlineMaterials and Methods: Methanolic extract of Lawsonia inermis (MELI) was prepared and newlinesubjected to preliminary phytochemical and HPLC analysis. In vitro antioxidant activity of MELI newlinewas performed using various methods such as DPPH assay, nitric oxide assay, superoxide ion assay, newlinereducing power assay and FRAP assay. Hydroxyapetite alginate loaded Lawsonia inermis was newlineprepared and evaluated by release behaviour, drug entrapment capacity and SEM studies. The newlineprepared MELI nanocomposites were subjected to in vivo anticancer evaluation in Dimethyl newlineHydrazine (DMH) induced colon cancer and various biochemical parameters were assessed. Further, newlineMELI-AuNPs nanocomposite was synthesized and characterized to evaluate the in vitro anti-colon newlinecancer activity in Caco2 colon cancer cell line. newlineResults: Preliminary phytochemical analysis of MELI reveals the presence of alkaloids, saponins, newlineglycosides, steroids, flavonoids and terpenoids. HPLC analysis of MELI shows the presence of newlineand#946;sitosterol. MELI displayed effective antioxidant by inhibiting DPPH, nitric oxide, superoxide ion newlinefree radicals, and showed strong reducing power potential in FRAP assay. The and#946;-Sitosterol loaded newlineHydroxyapatite-Alginate nanocomposite was confirmed by SEM imaging. Further, DMH induced newlinecolon cancer in rats have shown increased lipid peroxidation and decreased level of antioxidants such newlineas SOD, CAT, GST, GPX and GSH. The DMH intoxication showed altered haematological newlineincreased lipid profiles, tumour markers (AFP and CEA) and damage to colonic tissue confirmed by newlinehistopathology. Treatment with and#946;-Sitosterol nanocomposite at the dose of 50 and 100 mg/kg newlinesignificantly decreased the DMH induced colon carcinogenesis. Results of optimization showed that newlineHAuCl4 ion concentration of 1.5 mM, alkaline pH and incubation period of 20 min were the newlineoptimum conditions for AuNPs biosynthesis. The UV-visible spectrum shows a sharp peak at newline446 nm which was due to the surface plasmon resonance of the AuNPs. Effect of several newlinephytochemicals present in L. inermis, on the synthesis of AuNPs was studied by Fourier transform newlineinfrared spectroscopy. The results of TEM and XRD analysis showed that the synthesized AuNPs newlinewere mostly spherical in shape with a normal diameter of 44.3 ± 0.12 nm and highly crystalline in newlinenature. Additionally, the biosynthesized AuNPs were exhibited an excellent cytotoxic effect against newlineHCT-116 cell lines. newlineConclusion: The present study concludes that and#946;-Sitosterol loaded Hydroxyapatite-Alginate newlinenanocomposite and MELI-AuNPs serves as a suitable alternative agent with minimal adverse effects newlinefor the management of colon cancer.