A randomized, double-blind, parallel pharmacokinetic study comparing the trastuzumab biosimilar candidate, AryoTrust®, and reference trastuzumab in healthy subjects.

BACKGROUND: AryoTrust® (AryoGen Pharmed Co., Iran) is a biosimilar candidate for the EU-sourced reference trastuzumab, Herceptin®. This study was designed to evaluate the bioequivalence between AryoTrust® and Herceptin®. RESEARCH DESIGN AND METHODS: In this double-blind, parallel study, 60 healthy male subjects were randomized 1:1 to receive a single dose of AryoTrust® or Herceptin® (6 mg/kg) as intravenous infusion. The primary endpoint of the study was the area under the concentration versus time to infinity (AUC0-inf), and the main secondary endpoints were maximum measured concentration (Cmax), area under the concentration versus time from zero to the last quantifiable concentration time (AUC0-last), immunogenicity, and safety. RESULTS: Sixty subjects were enrolled in the study and baseline demographics were similar between the two groups. The two groups demonstrated similar pharmacokinetic parameters and the 90% confidence interval (CI) for primary and secondary endpoints were within the bioequivalence acceptance range (80.00%-125.00%). No serious adverse event or immunogenicity was reported, and all of the adverse events reported were mild and similar between the two treatment groups. CONCLUSION: AryoTrust® was well tolerated, had a similar safety profile to reference trastuzumab, and its pharmacokinetic bioequivalence was confirmed. TRIAL REGISTRATION: The trial is registered at Indian Trials Registry (CTRI/2019/03/018218).

PLGA-PEG-RA-based polymeric micelles for tumor targeted delivery of irinotecan.

To develop an effective therapeutic treatment, the potential of poly (lactic-co-glycolic acid)-polyethylene glycol-retinoic acid (PLGA-PEG-RA) polymeric micelles for targeted delivery of irinotecan to hepatocellular carcinoma (HepG2) and colorectal cancer cell lines (HT-29) was evaluated. PLGA-PEG-RA was synthesized by amide reaction of PLGA with NH2-PEG-NH2 and then PLGA-PEG-NH2 with RA and confirmed by FTIR and 1H NMR spectroscopy. Irinotecan-loaded nanomicelles were prepared using thin-film hydration method and the impact of various formulation variables on their particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE), and mean release time (MRT) were assessed using a Taguchi design. TEM was used to observe morphology of the nanomicelles and the CMC was determined by fluorescence spectroscopy. Adopted PLGA-PEG-RA nanomicelle exhibited PS of 160 ± 9.13 nm, PDI of 0.20 ± 0.05, ZP of -24.9 ± 4.03 mV, EE of 83.9 ± 3.61%, MRT of 3.28 ± 0.35 h, and CMC value of 25.7 µg/mL. Cytotoxicity of the targeted nanomicelles on HepG2 and HT-29 cell lines was significantly higher than that of non-targeted nanomicelles and the free drug. These results suggest that PLGA-PEG-RA nanomicelles could be an efficient delivery system of irinotecan for targeted therapy of colorectal cancer and hepatocellular carcinoma.