Animal poisons and venoms are comprised of different classes of molecules displaying wide-ranging pharmacological activities. This review aims to provide an in-depth view of toxin-based compounds from terrestrial and marine organisms used as diagnostic tools, experimental molecules to validate postulated therapeutic targets, drug libraries, prototypes for the design of drugs, cosmeceuticals, and therapeutic agents. However, making these molecules applicable requires extensive preclinical trials, with some applications also demanding clinical trials, in order to validate their molecular target, mechanism of action, effective dose, potential adverse effects, as well as other fundamental parameters. Here we go through the pitfalls for a toxin-based potential therapeutic drug to become eligible for clinical trials and marketing. The manuscript also presents an overview of the current picture for several molecules from different animal venoms and poisons (such as those from amphibians, cone snails, hymenopterans, scorpions, sea anemones, snakes, spiders, tetraodontiformes, bats, and shrews) that have been used in clinical trials. Advances and perspectives on the therapeutic potential of molecules from other underexploited animals, such as caterpillars and ticks, are also reported. The challenges faced during the lengthy and costly preclinical and clinical studies and how to overcome these hindrances are also discussed for that drug candidates going to the bedside. It covers most of the drugs developed using toxins, the molecules that have failed and those that are currently in clinical trials. The article presents a detailed overview of toxins that have been used as therapeutic agents, including their discovery, formulation, dosage, indications, main adverse effects, and pregnancy and breastfeeding prescription warnings. Toxins in diagnosis, as well as cosmeceuticals and atypical therapies (bee venom and leech therapies) are also reported. The level of cumulative and detailed information provided in this review may help pharmacists, physicians, biotechnologists, pharmacologists, and scientists interested in toxinology, drug discovery, and development of toxin-based products.

/pdf/from-animal-poisons-and-venoms-to-medicines-achievements-1ylb2fzykz.pdf

From Animal Poisons and Venoms to Medicines: Achievements, Challenges and Perspectives in Drug Discovery.

Thymoquinone (TQ), a phytochemical compound found in Carum carvil seeds (C. carvil), has a lot of applications in medical especially cancer therapy. However, TQ has a hydrophobic nature, and because of that, its solubility, permeability and its bioavailability in biological mediums are poor. To diminish these drawbacks, we have designed a herbal carrier composed of Ergosterol (herbal lipid), Carum carvil extract (Carum) and nonionic surfactants for herbal cancer treatment. C. carvil was extracted and characterized by GC/Mass. Two different formulations containing TQ and Carum were encapsulated into niosomes (Nio/TQ and Nio/Carum, respectively) and their properties were compared together. Morphology, size, zeta potential, encapsulation efficiency (EE%), profile release rate, in vitro cytotoxicity, flow cytometric, DNA fragmentation and cell migration assay of formulations were evaluated. Results show that both loaded formulations have a spherical morphology, nanometric size and negative zeta potential. EE% of TQ and Carum loaded niosomes was about 92.32% ± 2.32 and 86.25% ± 1.85, respectively. Both loaded formulations provided a controlled release compared with free TQ. MTT assay showed that loaded niosomes have more anti-cancer activity compared with Free TQ and free Carum against MCF-7 cancer cell line and these results were confirmed by flow cytometric analysis. Cell cycle analysis showed G2/M arrest in TQ, Nio/TQ and Nio/Carum formulations. TQ, Nio/TQ and Nio/Carum decreased the migration of MCF7 cells remarkedly. These results show that the TQ and Carum loaded niosomes are novel carriers with high efficiency for encapsulation of low soluble phytochemicals and also would be favourable systems for breast cancer treatment.

/pdf/evaluation-of-carum-loaded-niosomes-on-breast-cancer-cells-klxsf7qa0y.pdf

Evaluation of Carum-loaded Niosomes on Breast Cancer Cells:Physicochemical Properties, In Vitro Cytotoxicity, Flow Cytometric, DNA Fragmentation and Cell Migration Assay.

In Vivo Bio-Safety Evaluations and Diagnostic/Therapeutic Applications of Chemically Designed Mesoporous Silica Nanoparticles

Nanoparticulate-based drug delivery systems for small molecule anti-diabetic drugs: An emerging paradigm for effective therapy.

The use of phytochemicals to prevent or suppress tumours is known as chemoprevention. Numerous plant-derived agents have been reported to have anticancer potentials. As one such anticancer phytochemical, diosgenin has several applications which are nevertheless limited due to its low solubility in water. We loaded diosgenin into niosome to increase its solubility and hence efficiency. Diosgenin-niosome (diosgenin loaded into niosome) was prepared by thin-film hydration method and characterised by optical microscopy, dynamic light scattering (DLS), scanning electron microscopy (SEM), and UV-visible spectrophotometry. Also, loading efficiency, in vitro drug release, and cytotoxicity assay were performed on HepG2 cell line. Diosgenin-niosome has a nanometric size with a normal size distribution and spherical morphology. The loading efficiency of diosgenin was about 89% with a sustainable and controllable release rate. Finally, the viability of free diosgenin was 61.25%, and after loading into niosomes, it was improved to 28.32%. The results demonstrated that niosomes increase the solubility of naturally derived hydrophobic chemicals and thus enhance their anticancer effect.

https://link.springer.com/content/pdf/10.1007/s40199-019-00277-0.pdf

Diosgenin-loaded niosome as an effective phytochemical nanocarrier: physicochemical characterization, loading efficiency, and cytotoxicity assay

The invention relates to a method for preparing a fluorescent single-labeled cobra neurotoxin. The method comprises the following steps: on the basis of taking FITC (fluorescein isothiocyanate) as a derivatizing agent, carrying out a derivatization reaction on cobra neurotoxin (Neurotoxin, NT) and FITC at a molar ratio of 1:(1-1.2) in a buffer solution with the pH of 8.4-8.6 at a temperature of 20-40 DEG C for 8-10h, and separating and purifying a reaction solution to obtain a fluorescent single-labeled cobra neurotoxin. The preparation method provided by the invention is simple and rapid, the prepared FITC-NT has higher purity (more than 90%), a technical support is provided for improving the safety of an NT preparation and studying the intracorporal process of NT and a preparation thereof, and a reference is provided for the preparation and separation and purification study on a fluorescent single-labeled product of a macromolecular biological polypeptide.

Method for preparing fluorescent single-labeled cobra neurotoxin

Exenatide (EXT), the first glucagon-like peptide-1 receptor agonist, has been approved as an adjunctive therapy for patients with type 2 diabetes. Due to EXT’s short half-life, EXT must be administrated by continuous subcutaneous (s.c.) injection twice daily. In previous studies, many studies on EXT loaded into polymer materials carriers for sustained release had been reported. However, these carriers have some defects, such as hydrophobicity, low surface energy, low mechanical strength, and poor chemical stability. Therefore, this study aims to develop a novel drug delivery system, which is EXT loaded into well-ordered hexagonal mesoporous silica structures (EXT-SBA-15), to control the sustainability of EXT. SBA-15 was prepared by hydrothermal method with uniform size. Morphology of SBA-15 was employed by transmission electron microscopy. The pore size of SBA-15 was characterized by N2 adsorption–desorption isotherms. The in vitro drug release behavior and pharmacokinetics of EXT-SBA-15 were investigated. Furthermore, the blood glucose levels of diabetic mice were monitored after subcutaneous injection of EXT-Sol and EXT-SBA-15 to evaluate further the stable hypoglycemic effect of EXT-SBA-15. EXT-SBA-15 showed a higher drug loading efficiency (15.2 ± 2.0%) and sustained-release features in vitro. In addition, pharmacokinetic studies revealed that the EXT-SBA-15 treatment group extended the half-life t
 1/2(β) to 14.53 ± 0.70 h compared with that of the EXT solution (EXT-Sol) treatment group (0.60 ± 0.08 h) in vivo. Results of the pharmacodynamics study show that the EXT-SBA-15 treatment group had inhibited blood glucose levels below 20 mmol/L for 25 days, and the lowest blood glucose level was 13 mmol/L on the 10th day. This study demonstrates that the EXT-SBA-15 delivery system can control the sustainability of EXT and contribute to improve EXT clinical use.

https://link.springer.com/content/pdf/10.1186%2Fs40199-017-0186-9.pdf

Sustained-release study on Exenatide loaded into mesoporous silica nanoparticles: in vitro characterization and in vivo evaluation

Neurotoxin (NT), a short-chain α-neurotoxin, is the main neurotoxic protein identified from the venom of Naja naja atra. As an effective drug for the analgesis of advanced cancer patients, NT lasts longer than morphine and does not cause addiction. However, achieving a sensitive and high-resolution measurement of NT is difficult because of the extra-low content of NT in vivo. Therefore, developing a novel method to quantify NT is essential to study its pharmacokinetics in vivo. Although NT contains four primary amine groups that could react with the thiourea in fluorescein isothiocyanate (FITC), we developed a simple and reproducible single-label fluorescent derivatization method for NT which is related to the reaction of N-terminal α-amino of NT alone under optimized derivatization conditions. Furthermore, neurotoxin labelled with fluorescein isothiocyanate (NT-FITC) was prepared by high-performance liquid chromatography (HPLC) with a purity value higher than 99.29% and identified by MALDI-TOF/TOF-MS. Finally, NT-FITC could be detected at 0.8 nmol L−1 in rat plasma using capillary electrophoresis coupled with laser induced fluorescence detection (CE-LIF). In this paper, the established method robustly and reliably quantified NT labelled with FITC via intravenous and intramuscular administrations in vivo. In addition, this work fully demonstrated the pharmacokinetic characteristics of NT in vivo, which could reduce the risk of drug accumulation, optimize therapies, and provide sufficient evidence for the rational use of NT in clinical and research laboratories.

A single-label fluorescent derivatization method for quantitative determination of neurotoxin in vivo by capillary electrophoresis coupled with laser-induced fluorescence detection

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Method for preparing fluorescent single-labeled cobra neurotoxin

Sustained-release study on Exenatide loaded into mesoporous silica nanoparticles: in vitro characterization and in vivo evaluation

A single-label fluorescent derivatization method for quantitative determination of neurotoxin in vivo by capillary electrophoresis coupled with laser-induced fluorescence detection