Parenteral iron nutrition: Iron dextran-poloxamer thermosensitive hydrogel for prolonged intramuscular iron supplementation.

Autor: Durán E; Escuela de Medicina Veterinaria, Facultad de Recursos Naturales y Medicina Veterinaria, Universidad Santo Tomás, Ejercito Libertador 146, Santiago 8370003, Chile; Departamento de Fomento de la Producción Animal, Facultad de Ciencias Veterinarias y Pecuarias, Universidad de Chile, Santa Rosa 11.735, La Pintana, Santiago, Chile; Programa de Doctorado en Ciencias Silvoagropecuarias y Veterinarias, Campus Sur Universidad de Chile, Santa Rosa 11.315, La Pintana, Santiago CP: 8820808, Chile., Sepúlveda M; Departamento de Fomento de la Producción Animal, Facultad de Ciencias Veterinarias y Pecuarias, Universidad de Chile, Santa Rosa 11.735, La Pintana, Santiago, Chile., Romero-Hasler P; Departamento de Química Orgánica y Fisicoquímica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Olivos 1.007, Independencia, Santiago, Chile., Valdés F; Departamento de Fomento de la Producción Animal, Facultad de Ciencias Veterinarias y Pecuarias, Universidad de Chile, Santa Rosa 11.735, La Pintana, Santiago, Chile., Villamizar Sarmiento MG; Departamento de Ciencias y Tecnología Farmacéuticas, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santos Dumont 964, Independencia, Santiago, Chile., Soto-Bustamante E; Departamento de Química Orgánica y Fisicoquímica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Olivos 1.007, Independencia, Santiago, Chile., Neira-Carrillo A; Laboratorios de Materiales Bio-relacionados (CIMAT) y Síntesis y Caracterización de Polímeros Funcionalizados y Biomoléculas (POLYFORMS), Departamento de Ciencias Biológicas Animales, Facultad de Ciencias Veterinarias y Pecuarias, Universidad de Chile, Santa Rosa 11.735, La Pintana, Santiago, Chile., Neira V; Departamento de Medicina Preventiva, Facultad de Ciencias Veterinarias y Pecuarias, Universidad de Chile, Santa Rosa 11.735, La Pintana, Santiago, Chile., Ignacio Covarrubias J; Departamento de Producción Agrícola, Facultad de Ciencias Agronómicas, Universidad de Chile, Santa Rosa 11.315, La Pintana, Santiago, Chile., Oyarzun-Ampuero F; Departamento de Ciencias y Tecnología Farmacéuticas, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santos Dumont 964, Independencia, Santiago, Chile., Burgess DJ; Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, 69 North Eagleville Road, Storrs, CT 06269, USA., Valenzuela C; Departamento de Fomento de la Producción Animal, Facultad de Ciencias Veterinarias y Pecuarias, Universidad de Chile, Santa Rosa 11.735, La Pintana, Santiago, Chile. Electronic address: cvalenzuelav@u.uchile.cl.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 Sep 30; Vol. 663, pp. 124559. Date of Electronic Publication: 2024 Aug 08.
DOI: 10.1016/j.ijpharm.2024.124559
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: