Chitosan nanoparticles have been extensively utilised as polymeric drug carriers in nanoparticles formulations due to their potential to enhance drug delivery, efficacy, and safety. Numerous toxicity studies have been previously conducted to assess the safety profile of chitosan-based nanoparticles. These toxicity studies employed various methodologies, including test animals, interventions, and different routes of administration. This review aims to summarise research on the safety profile of chitosan-based nanoparticles in drug delivery, with a focus on general toxicity tests to determine LD50 and NOAEL values. It can serve as a repository and reference for chitosan-based nanoparticles, facilitating future research and further development of drugs delivery system using chitosan nanoparticles. Publications from 2014 to 2024 were obtained from PubMed, Scopus, Google Scholar, and ScienceDirect, in accordance with the inclusion and exclusion criteria.The ARRIVE 2.0 guidelines were employed to evaluate the quality and risk-of-bias in the in vivo toxicity studies. The results demonstrated favourable toxicity profiles, often exhibiting reduced toxicity compared to free drugs or substances. Acute toxicity studies consistently reported high LD50 values, frequently exceeding 5000 mg/kg body weight, while subacute studies typically revealed no significant adverse effects. Various routes of administration varied, including oral, intravenous, intraperitoneal, inhalation, and topical, each demonstrating promising safety profiles.

Alpha mangostin (AM), the main xanthone derivative contained in mangosteen pericarp (Garcinia mangostana/GM), has many pharmacological activities such as antioxidant, antiproliferation, antiinflammatory, and anticancer. Several general toxicity studies of AM have been previously reported to assess the safety profile of AM. Toxicity studies were carried out by various methods such as on test animals, interventions, and various routes of administration, but the test results have not been well documented. Our study aimed to systematically summarizes research on the safety profile of GM containing AM through general toxicity tests to get the LD₅₀ and NOAEL values, and so, can be used as a database related to AM toxicity profiles. This could facilitate other researchers in determining further development of GM-or-AM-based products. Pubmed, Google scholar, ScienceDirect, and EBSCO were chosen to collect the articles while ARRIVE 2.0 was used to evaluate the quality and risk-of-bias of the in vivo toxicity studies included in this systematic review. A total of 20 articles met the eligibility criteria and were reviewed to predict the LD₅₀ and NOAEL of AM. The results showed that the LD₅₀ of AM is between >15.480 mg/kgBW to ≤6000 mg/kgBW while the NOAEL value is between <100 and ≤2000 mg/kgBW.

Lignosus rhinocerotisCooke. (L.rhinocerotis) is a medicinal mushroom traditionally used in the treatment of asthma and several other diseases by the indigenous communities in Malaysia. In this study, the effects ofL.rhinocerotison allergic airway inflammation and hyperresponsiveness were investigated.L.rhinocerotisextract (LRE) was prepared by hot water extraction using soxhlet. Airway hyperresponsiveness (AHR) study was performed in house dust mite (HDM)-induced asthma in Balb/c mice while airway inflammation study was performed in ovalbumin (OVA)-induced asthma in Sprague-Dawley rats. Treatment with different doses of LRE (125, 250 and 500 mg/kg) significantly inhibited AHR in HDM-induced mice. Treatment with LRE also significantly decreased the elevated IgE in serum, Th2 cytokines in bronchoalveolar lavage fluid and ameliorated OVA-induced histological changes in rats by attenuating leukocyte infiltration, mucus hypersecretion and goblet cell hyperplasia in the lungs. LRE also significantly reduced the number of eosinophils and neutrophils in BALF. Interestingly, a significant reduction of the FOXP3⁺regulatory T lymphocytes was observed following OVA induction, but the cells were significantly elevated with LRE treatment. Subsequent analyses on gene expression revealed regulation of several important genes i.e.IL17A,ADAM33,CCL5,IL4,CCR3,CCR8,PMCH,CCL22,IFNG,CCL17,CCR4,PRG2,FCER1A,CLCA1,CHIAandCma1which were up-regulated following OVA induction but down-regulated following treatment with LRE. In conclusion, LRE alleviates allergy airway inflammation and hyperresponsiveness, thus suggesting its therapeutic potential as a new armamentarium against allergic asthma.

Background: The study was aimed to elucidate the influence of passage number of 4T1 cells for the development of the ideal tumour model. Methods: A total of 24 female BALB/c mice was divided equally into three groups: i) control (phosphate buffered saline [PBS] only); ii) group A (subjected to 4T1 cells of passage number 9) and iii) group B (subjected to 4T1 cells of passage number 10). The injections were introduced at the 3rd mammary pad of the mice. The net volume of the tumours was examined. Histopathological analysis was conducted to compare the extent of metastasis in the different groups of mice. Results: Group B had a higher net volume of 4T1 tumour as compared to group A (P = 0.042). The coefficient of variation in the net volume of 4T1 tumour for group A was higher (135.3%) as compared to group B (40.79%). Group A only exhibited metastasis on the lungs, liver and spleen whereas group B showed metastasis to the heart, spleen, lungs and liver. Conclusion: The use of 4T1 cells from passage number 10 is more ideal for the development of 4T1 tumour.

Nav1.5 is one of the nine voltage-gated sodium channel-alpha subunit (VGSC-α) family members. The Nav1.5 channel typically carries an inward sodium ion current that depolarises the membrane potential during the upstroke of the cardiac action potential. The neonatal isoform of Nav1.5, nNav1.5, is produced via VGSC-α alternative splicing. nNav1.5 is known to potentiate breast cancer metastasis. Despite their well-known biological functions, the immunological perspectives of these channels are poorly explored. The current review has attempted to summarise the triad between Nav1.5 (nNav1.5), breast cancer, and the immune system. To date, there is no such review available that encompasses these three components as most reviews focus on the molecular and pharmacological prospects of Nav1.5. This review is divided into three major subsections: (1) the review highlights the roles of Nav1.5 and nNav1.5 in potentiating the progression of breast cancer, (2) focuses on the general connection between breast cancer and the immune system, and finally (3) the review emphasises the involvements of Nav1.5 and nNav1.5 in the functionality of the immune system and the immunogenicity. Compared to the other subsections, section three is pretty unexploited; it would be interesting to study this subsection as it completes the triad.

Neonatal Nav1.5 (nNav1.5) is the alternative splice variant of Nav1.5 and it has been widely associated with the progression of breast cancer. The immunological context of nNav1.5 with respect to breast cancer metastases remains unexplored. The presence of antibodies against nNav1.5 may highlight the immunogenicity of nNav1.5. Hence, the aim of the present study was to detect the presence of antineonatal Nav1.5 antibodies (antinNav1.5‑Ab) in the serum of patients with breast cancer and to elucidate the effects of breast cancer therapy on its expression. A total of 32 healthy female volunteers and 64 patients with breast cancer were randomly recruited into the present study as the control and breast cancer group, respectively. Patients with breast cancer were divided equally based on their pre‑ and ongoing‑treatment status. Serum samples were tested with in‑house indirect enzyme‑linked immunosorbent assay (ELISA) to detect antinNav1.5‑Ab, CD25 (T regulatory cell marker) using an ELISA kit and Luminex assay to detect the expression of metastasis‑associated cytokines, such as vascular endothelial growth factor (VEGF), interleukin (IL)‑6, IL‑10, IL‑8, chemokine (C‑C motif) ligand 2 and tumor necrosis factor‑alpha (TNF‑α) The mean difference in the expression of antinNav1.5‑Ab among the three groups (control, pretreatment and ongoing‑treatment) was significant (P=0.0005) and the pretreatment breast cancer group exhibited the highest expression. The concentration of CD25 was highest in the pretreatment breast cancer group compared with the control and ongoing‑treatment groups. There was a significant positive correlation between antinNav1.5‑Ab and IL‑6 in the pretreatment group (r=0.7260; P=0.0210) and a significant negative correlation between antinNav1.5‑Ab and VEGF in the ongoing‑treatment group (r=‑0.842; P‑value=0.0040). The high expression of antinNav1.5‑Ab in the pretreatment group was in accordance with the uninterrupted presence of metastasis and highlighted the immunogenicity of nNav1.5 whereas the low expression of antinNav1.5‑Ab in the ongoing‑treatment group reflected the efficacy of breast cancer therapy in eliminating metastases. The augmented manifestation of T regulatory cells in the pretreatment group highlighted the functional role of nNav1.5 in promoting metastasis. The parallel expression of antinNav1.5‑Ab with the imbalanced expression of cytokines promoting metastasis (IL‑8, IL‑6 and TNF‑α) and cytokines that prevent metastasis (IL‑10) indicated the role of nNav1.5 in breast cancer growth. The expression of antinNav1.5‑Ab in accordance to the metastatic microenvironment indicates the immunogenicity of the protein and highlights the influence of breast cancer therapy on its expression level.