Preclinical safety of negatively charged microspheres (NCMs): Optimization of radiolabeling for in vivo and ex vivo biodistribution studies after topical administration on full-thickness wounds in a rat model

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 177; pp. 61 - 67
• Main Authors: Collantes, María, Vairo, Claudia, Erhard, Álvaro, Navas, Cristina, Villullas, Silvia, Ecay, Margarita, Pareja, Félix, Quincoces, Gemma, Gainza, Garazi, Peñuelas, Iván
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2022
• Subjects: Biodistribution; Negatively charged microspheres; Radiolabeling; Technetium-99m; Topical administration; Wound; DTPA; Radiolabeling; TLC; SnCl2; VOIs; Wound; Biodistribution; Technetium-99m; SPECT; SPECT/CT; [99mTc]TcO4; Negatively charged microspheres; 99mTc-NCMs; Topical administration; NCMs; biodistribution; wound; radiolabeling; negatively charged microspheres; topical administration; technetium-99m
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2022.06.001

[Display omitted] Negatively charged microspheres (NCMs) are postulated as a new form of treatment for chronic wounds. Despite the efficacy shown at clinical level, more studies are required to demonstrate their safety and local effect. The objective of the work was to confirm the lack of NCM systemic absorption performing a biodistribution study of the NCMs in an open wound rat animal model. To this end, radiolabeling of NCMs with technetium-99 m was optimized and biodistribution studies were performed by in vivo SPEC/CT imaging and ex vivo counting during 24 h after topical administration. The studies were performed on animals treated with a single or repeated dose to study the effect of macrophages during a prolonged treatment. NCM radiolabeling was achieved in a simple, efficient and stable manner with high yield. SPECT/CT images showed that almost all NCMs (about 85 %) remained on the wound for 24 h either after single or multiple administrations. Ex vivo biodistribution studies confirmed that there was no accumulation of NCMs in any organ or tissue except in the wound area, suggesting a lack of absorption. In conclusion, NCMs can be considered safe as local wound treatment since they remain at the administration area.