title: Preclinical systemic toxicity evaluation of chitosan-solid lipid nanoparticle-encapsulated aspirin and curcumin in combination with free sulforaphane in BALB/c mice.
abstract: Our previous studies have established the efficacy of chemopreventive regimens of aspirin and curcumin (CUR) encapsulated within solid lipid nanoparticles (SLNs) in combination with free sulforaphane (ACS combination) to prevent or delay the initiation and progression of pancreatic cancer, classified as one of the deadliest diseases with very low chances of survival upon diagnosis. Although toxicity of individual drugs and SLN has been studied previously, there are no studies in current literature that evaluate the potential toxicity of a combined regimen of ACS, especially when encapsulated within chitosan-SLNs (c-SLNs). Hence, objective of the current study was to investigate the potential toxic effects of ACS c-SLN combined chemopreventive regimens following acute (3 days), subacute (28 days), and subchronic (90 days) administrations by oral gavage in BALB/c mice. Mice were administered the following regimens: saline, blank c-SLN, low-dose ACS c-SLN (2+4.5+0.16 mg/kg), medium-dose ACS c-SLN (20+45+1.6 mg/kg), and high-dose ACS c-SLN (60+135+4.8 mg/kg). The potential toxicity was evaluated based on animal survival, body weight, hematology, blood chemistry, and organ histopathology. During 3-day, 28-day, and 90-day study periods, no animal deaths were observed. Treatment with ACS c-SLNs did not cause alteration in complete blood counts and blood chemistry data. Histopathological examination of various organ sections (pancreas, heart, liver, kidney, and brain) appeared normal. Based on the results of this study, no signs of toxicity in acute, subacute, and subchronic studies following oral administration of ACS c-SLNs were found indicating that the oral dosing regimens were safe at the levels tested for long-term administration to prevent the onset of pancreatic cancer.
authors: Department of Pharmaceutical Sciences, College of Pharmacy.
authors: Arvind
authors: A
authors: Thakkar
authors: Department of Pharmaceutical Sciences, College of Pharmacy.
authors: Sushma
authors: S
authors: Chenreddy
authors: Department of Pharmaceutical Sciences, College of Pharmacy.
authors: Astrid
authors: A
authors: Thio
authors: College of Veterinary Medicine, Western University of Health Sciences, Pomona, CA, USA.
authors: Wael
authors: W
authors: Khamas
authors: Department of Pharmaceutical Sciences, College of Pharmacy.
authors: Jeffrey
authors: J
authors: Wang
authors: Department of Pharmaceutical Sciences, College of Pharmacy.
authors: Sunil
authors: S
authors: Prabhu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D048271:Chitosan / Q000633:toxicity*; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D065546:Drug Liberation; D005260:Female; D017879:Isothiocyanates / Q000008:administration & dosage / Q000494:pharmacology*; D008055:Lipids / Q000633:toxicity*; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000633:toxicity*; D010316:Particle Size; D055672:Static Electricity; D013454:Sulfoxides; D018675:Toxicity Tests
chemical_list: D017879:Isothiocyanates; D008055:Lipids; D013454:Sulfoxides; D048271:Chitosan; C016766:sulforaphane; D003474:Curcumin; D001241:Aspirin
keywords: aspirin; chitosan-solid lipid nanoparticle; curcumin; pancreatic cancer; sulforaphane; toxicity