Influence of halloysite nanotubes on the efficiency of Asparaginase against mice Ehrlich solid carcinoma

Abstract

Herein, the impact of the halloysite nanotubes to suppress the side effects of Asparaginase (ANase) cellular proliferation was investigated. Methods: A total of 100 adult male mice was employed. These mice were divided into four equal groups; Group 1 (control), Group 2 (ESC group) of a single dose of 0.15 ml Ehrlich cells (2 × 10⁶) intraperitoneal infusion(IP), Group 3 (ESC + ANase group) received six doses equal treatments of Intratumoral (IT) 0.07 ml Aspragnase (7 mg/kg) over two weeks. For two weeks, Group 4 (ESC + ASNase + HNTs) received an IT administration of 0.07 ml Asparaginase stocked on Halloysite nanotubes (HNTs) (30 mg/kg) three times per week. A blood specimen was collected, and the liver was removed to be investigated histologically. Results: TEM measurements for the Halloysite nanoclay showed their tubular cylindrical shape with a mean diameter of 50 nm and an average length of 1 μm, whereas The X-ray diffraction pattern of the Halloysite nanoclay showed their characteristic peaks. ESC increases the serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and bilirubin than control and other groups, even as albumin and total protein were decreasing. After using Halloysite Nanotube, the rates of these variables were enhanced up to 75%. The hepatocytes histological studies showed protection against Ehrlich Solid carcinoma-induced degenerative, necrotic, and inflammatory changes up to 70%. In conclusion, halloysite nanotubes have demonstrated effective removal of Ehrlich solid carcinoma in mice using an ASNase delivery system. It promoted the ASNase to inhibit the adverse effect of ANase's on the liver and remove the tumour cells.

Keywords: ALB, Albumin; ALP, Alkaline Phosphatase; ALT, Aniline Aminotransferase; ASNase, Asparaginase; AST, Aspartate Aminotransferase; Asparaginase; BCP, bromocresol purple; BD, Bile Duct; CV, Central Vein; DDS, Drug Delivery Systems; EAC, Ehrlich ascites carcinoma; ESC, Ehrlich Solid Carcenoma; HNTs, Halloysite Nanotubes; Halloysite nanotubes, Cancer; Histopathology; IFCC, international federation of clinical chemistry; IM, Intramuscularly; IP, Intraperitoneal; IT, Intratumorally; KAU, King Abdulaziz University; KFMRC, King Fahd Medical Research Center; Liver; Liver functions; PV, Portal Vein; TBIL, Total Bilirubin; TEM, Transmission Electron Microscope; TP, Total protein; XRD, X-Ray Diffraction.

Fig. 1

Transmission Electron Microscope micrographs of Halloysite Nanotubes at different magnification power.

Fig. 2

X-ray diffraction pattern of halloysite Nanoclay.

Fig. 3

Mice liver stained sections by Hematoxylin and eosin were photographed at different magnification powers (X100 & X400) for G1, G2, G3, and G4.

Fig. 4

Difference between all studied groups among liver functions in adult male albino mice.