Poly (lactic-co-glycolic acid)-3-amino-1-propane sulfonic acid conjugates: A promising strategy to prevent biofilm formation of fluconazole-resistant Candida albicans

Abstract

The formation of biofilm of Candida albicans is the main cause of life-threatening infections, leading to drug failure. Conjugate nanocarriers have demonstrated a good trend in preventing clinical problems of drug resistance through their effective penetration and retention inside biofilms. In this study, we aimed to prepare a conjugate comprising PLGA and sulfonic-functionalized molecule tramiprosate (p-TPS) via coupling reaction to improve the long-term effect and effectiveness of the conjugate against the C. albicans-associated biofilm. The safety profile of p-TPS was evaluated through in vitro cell-based assays, in vivo Caenorhabditis elegans toxicity studies, and biodistribution analyses. The results demonstrated that the prepared conjugate presented in vitro cellular protection and exhibited a favorable in vivo survivability profile in C. elegans. Dye-labeled p-TPS exhibited in vivo distribution in albino Wistar rats' bodies within 1 h. Cellular uptake studies revealed a considerable cellular uptake range. The improved p-TPS efficiently prevented the formation of a biofilm of fluconazole-resistant C. albicans. Hyphae were dramatically arrested after the treatment by p-TPS. The collective outcomes suggest that the prepared p-TPS conjugate is a good candidate for an antibiofilm effect against C. albicans. Thus, this research demonstrated a new approach for preventing Candida-associated biofilm infections. © 2025 Elsevier B.V., All rights reserved.