Preclinical evaluation of albendazole albumin nanoparticles for the treatment of ovarian cancer (In vitro and In vivo assessment)

The poor prognosis of patients with drug resistant ovarian cancer and the lack of targeted therapy have raised the need for alternative treatments. Albendazole (ABZ) is an anti-helminthic capable of impairing microtubule formation and has been shown to suppress tumor growth in a number of preclinical studies. Hence, we hypothesized that ABZ could be used as a potential anti-angiogenic drug since it is a potent inhibitor of vascular endothelial growth factor (VEGF) in ovarian cancer with ascites. However, ABZ’s low aqueous solubility limits its potential in cancer therapy. To improve ABZ’s solubility we have prepared ABZ-bovine serum albumin nanoparticles, with a size range of 7-10 nm, 200-250 nm and 200-300 nm cross-linked with glutaraldehyde. The larger nab-ABZ 200-300 nm cross-linked nanoparticles (NPs) were initially formulated. Although in vitro results were positive but in vivo no significant efficacy was observed. We then prepared smaller sized NPs and examined the anticancer effects using ovarian cancer cells in both in vitro and in vivo models. Drug release studies demonstrated that about 93% of ABZ was released from BSA-ABZ 10 nm in comparison to 83% from Nab-ABZ 200 nm at pH 7.4 in 8 days. In vitro cell proliferation studies showed that the BSA-ABZ 10 nm exhibited the highest cytotoxicity in ovarian cancer cells with surprisingly the least toxicity to healthy ovarian epithelial cells. Confocal microscopy and fluorescence activated cell sorting analysis (FACS) revealed more efficient internalization of the BSA-ABZ 10 nm by cancer cells. In in vivo settings, we examined the tumor growth, ascites formation and the expression of VEGF and secreted protein acidic and rich in cysteine (SPARC) in tumor samples and VEGF in plasma samples. The BSA-ABZ 10 nm significantly reduced the tumor burden (p<0.02) even at a much lower drug dose (10 μg/ml) compared to free drug due to better uptake Nab-ABZ 200 nm and BSA-ABZ 10 nm both were capable of suppressing the ascites volume significantly (p<0.05) and reducing the number of ascites cells. Our data suggest that amongst the different sizes of nano particles, the smaller BSA-ABZ 10 nm may hold promise in the treatment of ovarian cancer with ascites

Albumin nanoparticles increase the anticancer efficacy of albendazole in ovarian cancer xenograft model

Background: The poor prognosis of patients with drug resistant ovarian cancer and the lack of targeted therapy have raised the need for alternative treatments. Albendazole (ABZ) is an anti-parasite compound capable of impairing microtubule formation. We hypothesized that ABZ could be repurposed as a potential anti-angiogenic drug due to its potent inhibition of vascular endothelial growth factor (VEGF) in ovarian cancer with ascites. However, the poor aqueous solubility of ABZ limits its potential for cancer therapy. In this study, we have assembled ABZ with bovine serum albumin into nanoparticles with a size range of 7–10 nm (BSA-ABZ) and 200–250 nm (Nab-ABZ). We further examined the anticancer effects of ABZ carrying nanoparticles in ovarian cancer cells, in both in vitro and in vivo models. Results: Drug release studies demonstrated that about 93% of ABZ was released from BSA-ABZ 10 nm in comparison to 83% from Nab-ABZ 200 nm at pH 7.4 in 8 days. In vitro cell proliferation studies showed that the BSA-ABZ 10 nm exhibited the highest killing efficacy of ovarian cancer cells with surprisingly least toxicity to healthy ovarian epithelial cells. Confocal microscopy and fluorescence activated cell sorting analysis (FACS) revealed more efficient internalization of the BSA-ABZ 10 nm by cancer cells. For in vivo studies, we examined the tumor growth, ascites formation and the expression of VEGF and secreted protein acidic and rich in cysteine (SPARC) in tumor samples and only VEGF in plasma samples. The BSA-ABZ 10 nm reduced the tumor burden significantly (p < 0.02) at a much lower drug dose (10 μg/ml) compare to free drug. Both formulations were capable of suppressing the ascites volume significantly (p < 0.05) and reducing the number of ascites cells. The expression of VEGF and SPARC was also reduced, which indicates the underlying therapeutic mechanism of the ABZ. Conclusion: Our data suggest that the BSA-ABZ may hold promise for the treatment and control of progression of ovarian cancer with ascites. However further studies are required to examine the efficacy of both the formulations in aggressive models of recurrent ovarian cancer with respect to particle size and dosing parameters

Effect of anti-epileptic drugs on serum lipids in epileptic patients- A case-control study

Epilepsy is a chronic illness, thus antiepileptic drugs are often used extensively. However, this treatment may be linked to metabolic abnormalities in different body systems, including the endocrine system, connective tissues, and liver. Moreover, prolonged use of antiepileptic drugs may lead to adverse effects on serum lipid levels. This study was conducted to explore alterations in serum lipids after the administration of antiepileptic drugs in epileptic patients and compared with healthy volunteers. A total of 200 participants were selected; including 100 epileptic patients and 100 age, gender and locality matched controls having negative personal or family history of epilepsy. All the participants signed written informed consent and were interviewed through a standard questionnaire. Blood samples were collected from all participants, for the analysis of serum lipids. The accurate rapid test used to analyze samples of both groups. Significantly increased concentration of total lipids, total cholesterol, triglyceride and VLDL-C were found in epileptic patients as compared to controls and also in male epileptic patients, whereas, reverse was true for HDL-C. Significant variations were found for total cholesterol, HDL-C, LDL, triglycerides and VLDL-C in epileptic patients with age group 36 to 46 years, while, the HDL-C was significantly decreased in age group 15 to 35 years. Antiepileptic drugs, especially Episenta alters the serum lipid contents, but the total cholesterol was significantly altered among the users of antiepileptic drugs

Albendazole loaded albumin nanoparticles for ovarian cancer therapy

Albendazole (ABZ), a well-established antiparasitic drug, has been shown to suppress tumor growth in a number of preclinical models of cancer. However, the low solubility of ABZ limits its use as a systemic anticancer agent. To enable systemic administration, we have formulated ABZ into albumin nanoparticles with a size range of 200-300 nm, which were cross-linked with glutaraldehyde to stabilize the nanoparticles and to introduce pH-responsive features. Drug release studies demonstrated that about 20% of ABZ was released at neutral pH within a week in comparison to 70% at slightly acidic condition (pH 5). Cellular uptake studies using ovarian cancer cells indicated that nanoparticles were internalized efficiently within 1 h of incubation. Further, cell proliferation results demonstrated that albumin nanoparticles alone showed no cytotoxicity to both normal and cancer cells. In contrast, the drug-loaded nanoparticles exhibited cellular toxicity and high killing efficacy to cancer cells compared to normal cells. Collectively, our results suggest that these albumin nanoparticles may hold great potentials as ABZ carriers for cancer therapy