Isoflurophate

Iron chelating agents (ICs) such as conventional deferiprone are often ineffective when exposed to normal conditions due to their uncontrolled release when treating iron overload in ß-thalassemia major (ß-TM) due to the effects of blood transfusion. Iron deficiency and gastrointestinal side effects are crucial problems that can occur. Therefore, DFP was prepared as nanoparticles (NPs) coated with an iron-responsive (IR) polymer with an average particle size of 354.70 ± 10 nm to control its release. To facilitate optimal delivery, NP-IR-DFP was integrated into a dissolving microneedle (DMN) fabricated with biodegradable and biocompatible poly(vinylpyrrolidone) and poly(vinyl alcohol) polymers. The results showed that the NP-IR-DMN provided excellent insertion and mechanical strength and dissolved quickly after application. In vitro and ex-vivo studies revealed the more controllable release of NP-IR-DFP after integration with the DMN (NP-IR-DMN) for up to 24 h. Most importantly, the developed formula was hemocompatible and did not irritate the skin or cause tissue damage. Furthermore, the in vivo pharmacokinetics were further investigated for 24 h, which revealed short concentration (C_max of 0.07 ± 0.03 μg/mL) and t_1/2 (3.66 ± 0.76 h) under normal conditions and long-term iron overload-modeling conditions with C_max (2.90 ± 0.14 μg/mL) and t_1/2 (10.13 ± 1.00 h). This approach can extend beyond oral delivery by controlling the release of DFP, which can only be released in conditions of iron overload, and has the potential to prevent iron deficiency and excess, thus increasing the efficacy of DFP in β-TM therapy.

Ticks are a medically important group of arthropods, and their control has become a major challenge due to their widespread resistance to synthetic acaricides. Defatted seed meals of plants in the mustard family, commonly generated as byproducts of vegetable oil and biofuel production are known to possess pesticidal properties but their potential to control ticks remain poorly understood. We evaluated the bio-fumigation activity of defatted seed meals of three mustard family species, Brassica juncea (L) Czern. (PG), Lepidium sativum L. (Ls) and Thlaspi arvense L. (DFP), against three medically important hard tick species: Ambylomma americanum (L.) [Aa], Dermacentor variabilis (Say) [Dv] and Ixodes scapularis (Say) [Is]. Volatiles produced by defatted seed meals of the three plant species had strong bio-fumigation activity against ticks, but their effects varied among the three tick species. Toxicity of DFP seed meals was significantly different among the three tick species (no overlap of the 95% CI) with LD₅₀ values of 0.056 g for Aa nymphs, 0.031 g for Dv nymphs, and 0.037 g for Is nymphs. Defatted Ls seed meals were more toxic to Dv (LD₅₀ = 0.022 g) and Is (LD₅₀ = 0.018 g) nymphs compared to Aa nymphs (LD₅₀ = 0.035 g) while defatted PG seed meals were more toxic to Is nymphs (LD₅₀ = 0.009 g) compared to Aa (LD₅₀ = 0.048 g) and Dv (LD₅₀ = 0.032 g) nymphs. This study is the first report to document that defatted Brassicaceae seed meals are a promising plant-based biofumigant for tick control that can be developed as a cheap, practical, and ecofriendly acaricide.