In-vivo anticancer efficacy of self-targeted methotrexate-loaded polymeric nanoparticles in solid tumor-bearing rat.

ABSTRACT

Here, cytotoxicity and antitumor efficacy against a chemically (N-methyl-N-nitrosourea) generated mammary tumor in rats were assessed using methotrexate-loaded chitosan nanoparticles (Meth-Cs-NPs). Meth-Cs-NPs intravenous administrated resulted in noticeably decreased tumor incidence, multiplicity, and weight. Further, kidney function tests for the treated groups resulted in noticeably decreased ALP (Meth-Cs-NPs; 244 ± 15, diseases control; 403 ± 14 U/L), Creatinine (Meth-Cs-NPs; 0.81 ± 0.05, diseases control; 2 ± 0.05 mg/dl), and Urea (Meth-Cs-NPs; 56.62 ± 5, diseases control; 113 ± 6 mg/dl) levels, close to a normal control group. Similarly, liver function tests showed significantly decreased serum biomarkers, SGPT (Meth-Cs-NPs; 40 ± 1.8, diseases control; 84 ± 1.9 U/L) and SGOT (Meth-Cs-NPs; 15 ± 2, diseases control; 55 ± 4 U/L) levels in treated groups as compared to the untreated group (diseases control). From the results, pro-inflammatory cytokines were also markedly reduced in the treated group such as, TNF-α (Meth-Cs-NPs; 17.31 ± 1.15, diseases control; 36.9 ± 5 pg/mL), IL-1ß (Meth-Cs-NPs; 433.3 ± 66.5, diseases control; 1540 ± 131.1 pg/mL), and IL-6 (Meth-Cs-NPs; 1515 ± 53, diseases control; 2200.6 ± 69 pg/mL) levels. Whereas Meth-Cs-NPs not only helped in lowering tumor multiplicity rates but also decrease inflammation. The studies could be successfully performed in chemically induced mammary tumors due to their easy, quick tumor growth and low mortality rates in rat models. According to the current study, Meth-Cs-NPs have high treatment potency and represent a possible therapeutic alternative for breast cancer treatment.