Synthesis and Antitumor Activity of Doxycycline Polymeric Nanoparticles: Effect on Tumor Apoptosis in Solid Ehrlich Carcinoma.

OBJECTIVES: The aim of this study was to prepare doxycycline polymeric nanoparticles (DOXY-PNPs) with hope to enhance its chemotherapeutic potential against solid Ehrlich carcinoma (SEC). METHODS: Three DOXY-PNPs were formulated by nanoprecipitation method using hydroxypropyl methyl cellulose (HPMC) as a polymer. The prepared DOXY-PNPs were evaluated for the encapsulation efficiency (EE%), the drug loading capacity, particle size, zeta potential (ZP) and the in-vitro release for selection of the best formulation. PNP number 3 was selected for further biological testing based on the best pharmaceutical characters. PNP3 (5 and 10 mg/kg) was evaluated for the antitumor potential against SEC grown in female mice by measuring the tumor mass as well as the expression and immunohistochemical staining for the apoptosis markers; caspase 3 and BAX. RESULTS: The biological study documented the greatest reduction in tumor mass in mice treated with PNP3. Importantly, treatment with 5 mg/kg of DOXY-PNPs produced a similar chemotherapeutic effect to that produced by 10 mg/kg of free DOXY. Further, a significant elevation in mRNA expression and immunostaining for caspase 3 and BAX was detected in mice group treated with DOXY-PNPs. CONCLUSIONS: The DOXY-PNPs showed greater antitumor potential against SEC grown in mice and greater values for Spearman's correlation coefficients were detected when correlation with tumor mass or apoptosis markers was examined; this is in comparison to free DOXY. Hence, DOXY-PNPs should be tested in other tumor types to further determine the utility of the current technique in preparing chemotherapeutic agents and enhancing their properties.

Antitumor activity of a molecularly imprinted nanopreparation of 5-flurouracil against Ehrlich's carcinoma solid tumors grown in mice: Comparison to free 5-flurouracil.

Recently, nanotechnology has received great attention in war against cancer. The present study investigated the antitumor efficacy of molecularly imprinted nanopreparation of 5-fluorouracil (nano-5-FU) against Ehrlich ascites carcinoma (EAC) solid tumors grown in mice. Tumor cells were transplanted into female albino mice. Mice were allocated into 5 groups; Group 1: control EAC bearing mice. Groups 2&3: EAC-bearing mice treated orally with 5-FU (5 and 10 mg/kg) twice weekly. Groups 4&5: EAC bearing mice treated with nano-5-FU (5 and 10 mg/kg) twice weekly. Treatment with nano-5-FU showed higher antitumor effect compared to free 5-FU as indicated by enhanced apoptosis and reduction in tumor weight. Additionally, lower number of mitotic figures and greater area for necrosis were observed in the tumor specimens alongside with a decline in the number of intratumoral proliferating nuclei in comparison to free 5-FU. Furthermore, the results showed a significant down-regulation in tumoral expression of caspase-3 and vascular endothelial growth factor. Together, these results further support the potential of using nanotechnology to enhance anticancer efficacy of 5-FU.