Abstract：
The objective of this study was to evaluate the potential of novel poloxamer thermosensitive hydrogels (PTHs) formulations for prolonged release of iron dextran particles (IDP) for intramuscular (IM) injection. The thermosensitive behaviour helps to avoid hepcidin overexpression and toxicity by releasing IDPs without iron accumulation in injection or deposit sites. We hypothesized that novel PTH formulation would prolong iron liberation compared to the commercial iron dextran formulation (FEDEX). PTHs loaded with IDPs were developed with increasing iron content (0.1, 0.2 and 0.4 g of iron/g of poloxamer) and characterized as a prolonged release IM iron supplement. The PTHs had a biocompatible pH for IM injection (6.4) and thermosensitive viscosity, increasing from ∼50 (4 °C) to ∼3000 mPa.s (37 °C). PTHs were successfully injected in the sol state (at 4 °C) into pork meat at 37 °C, transitioning to the gel state in situ (in ∼60-190 s). Structural characterization indicated that there were no PTH-IDP chemical interactions, suggesting that IDP entrapment in PTHs was physical upon gelation. In vitro release studies revealed that iron release from PTH (0.4 g of iron/g of poloxamer) reached 100 % by day 10, whereas 100 % release from FEDEX was complete in 4 h. This novel iron PTH formulation achieved a 60 times long iron release compared to the commercial product. In conclusion, the reported strategy shows adequate IDP entrapment/release properties for prolonged iron release following ex vivo IM injection using biocompatible materials. These results provide a strong basis for future preclinical evaluation to elucidate aspects such as drug release, local irritation, biocompatibility, and efficacy.
摘要：
这项研究的目的是评估新型泊洛沙姆热敏水凝胶（PTH）制剂用于肌内（IM）注射的葡聚糖铁颗粒（IDP）的延长释放的潜力。热敏行为通过释放IDP而在注射或沉积位点没有铁积累，有助于避免hepcidin过表达和毒性。我们假设与商业铁葡聚糖制剂(FEDEX)相比,新型PTH制剂将延长铁释放。负载有IDP的PTH随着铁含量的增加而发展（0.1、0.2和0.4g铁/g泊洛沙姆），其特征是延长释放IM铁补充剂。PTHs具有用于IM注射的生物相容性pH（6.4）和热敏粘度，从50(4°C)增加到3000mPa。s(37°C)。PTH在37°C下以溶胶状态（4°C）成功注入猪肉中，原位过渡到凝胶状态(在~60-190秒内)。结构表征表明，没有PTH-IDP化学相互作用，表明PTH中的IDP截留在凝胶化后是物理的。体外释放研究表明,铁从PTH的释放(0.4g铁/g泊洛沙姆)到第10天达到100%,而从FEDEX的100%释放在4小时内完成。与市售产品相比,这种新型铁PTH制剂实现了60倍长的铁释放。总之,报道的策略显示,在使用生物相容性材料的离体IM注射后,对于延长的铁释放,具有足够的IDP截留/释放特性.这些结果为未来临床前评估提供了强有力的基础，以阐明药物释放等方面。局部刺激,生物相容性，和功效。
