Controlled release of deferiprone using iron-responsive nanoparticles integrated with dissolving microneedle for novel alternative treatments of β-thalassemia major

Abstract

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.