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Curcuma xanthorrhiza Roxb, Phyllanthus niruri L., and Morinda citrifolia L. are Indonesian medicinal herbs used empirically as traditional therapeutics for maintaining health. The cocktail extract of these three plants (CECPM) had been developed and demonstrated immunostimulant activity in rats. This study aimed to evaluate the acute and subchronic toxicity of CECPM in vivo. The acute toxicity assay was conducted by orally administering a range dose of CECPM (313, 625, 1250, 2500, or 5000 mg/kg body weight (bw) on female mice once and then evaluating the toxic symptom every day for 14 days later. The chronic toxicity test was carried out by giving various doses of CECPM (600, 800, and 1000 mg/kg·bw) to female and male rats orally continuously for 90 consecutive days. The signs of toxicities were evaluated at the 90- and 28 days postadministration. The acute oral toxicity assays showed that there was no toxic syndrome and mortality found during the period of the experiment. The lethal dose level (LD50) of CECPM was more than 5000 g/kg, which was categorized as practically non-toxic. Meanwhile, in the sub-chronic toxicity study, some parameters tested at 90 days postadministration and after 28 days of withdrawal, such as the body weight, relative organ weight, food intake, hematological and biochemical blood parameters, and also histopathological examination of five primary tissues (heart, liver, kidney, spleen, and lung) revealed no abnormalities. There was no-observed adverse effect level (NOAEL) for the present study of CECPM 1000 mg/kg·bw of the rat. Therefore, it is concluded that the orally administered CECPM was relatively nontoxic during acute and subchronic toxicology studies. [ABSTRACT FROM AUTHOR]

Cancer cells have high iron requirements due to their rapid growth and proliferation. Iron depletion using iron chelators has a potential in cancer treatment. Previous studies have demonstrated that deferoxamine (DFO) specifically chelates Fe(III) and exhibited antitumor activity in clinical studies. However, its poor pharmacokinetics has limited the therapeutic potential and practical application. Although polymeric iron chelators have been developed to increase the blood retention, none of previous studies has demonstrated their potential in iron chelation cancer therapy. Here, we developed polymeric DFO by the covalent conjugation of DFO to poly(ethylene glycol)‐poly(aspartic acid) (PEG‐PAsp) block copolymers. The polymeric DFO exhibited iron‐chelating ability comparable with free DFO, thereby arresting cell cycle and inducing apoptosis and antiproliferative activity. After intravenous administration, the polymeric DFO showed marked increase in blood retention and tumor accumulation in subcutaneous tumor models. Consequently, polymeric DFO showed significant suppression of the tumor growth compared with free DFO. This study reveals the first success of the design of polymeric DFO for enhancing iron chelation cancer therapy. [ABSTRACT FROM AUTHOR]

Over recent decades, nanomedicine has played an important role in the enhancement of therapeutic outcomes compared to those of conventional therapy. At the same time, nanoparticle drug delivery systems offer a significant reduction in side effects of treatments by lowering the off-target biodistribution of the active pharmaceutical ingredients. Cancer nanomedicine represents the most extensively studied nanotechnology application in the field of pharmaceutics and pharmacology since the first nanodrug for cancer treatment, liposomal doxorubicin (Doxil ® ), has been approved by the FDA. The advancement of cancer nanomedicine and its enormous technological success also included various other target diseases, including hepatic fibrosis. This confirms the versatility of nanomedicine for improving therapeutic activity. In this review, we summarize recent updates of nanomedicine platforms for improving therapeutic efficacy regarding liver fibrosis. We first emphasize the challenges of conventional drugs for penetrating the biological barriers of the liver. After that, we highlight design principles of nanocarriers for achieving improved drug delivery of antifibrosis drugs through passive and active targeting strategies., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024, Setyawati et al.)