Mannose-functionalized Clofazimine-loaded Nanostructured Lipid Carriers for Cutaneous Leprosy: development and in vitro evaluation.
Authorship
C.E.E.
Master's Degree in Drug Research and Development
C.E.E.
Master's Degree in Drug Research and Development
Defense date
02.20.2026 10:00
02.20.2026 10:00
Summary
Leprosy is a neglected tropical disease with persistent transmission in endemic regions, where treatment effectiveness is limited by adverse effects and poor patient adherence. Clofazimine (CFZ), a key component of the World Health Organization recommended multidrug therapy, exhibits low aqueous solubility, high tissue accumulation and causes skin pigmentation. To overcome these limitations, this study focused on the development of clofazimine loaded nanostructured lipid carriers functionalized with mannose (MAN-CFZ NLCs) for the local treatment of intracellular infections in dermal macrophages. The NLCs were prepared by hot homogenization, functionalized with mannose to promote macrophage uptake and physicochemically characterized. The in vitro biocompatibility of the formulations was evaluated in fibroblast and macrophage cell lines. Finally, NLC internalization studies were performed in resting (M0) and activated (M1) macrophages. The results showed that the developed nanosystems exhibited a nanometric size of approximately 150 nm, high monodispersity (PDI less than 0.2) and a notable CFZ loading capacity of about 4 percent. Biocompatibility assessment demonstrated good in vitro tolerability of the formulations, while internalization assays revealed enhanced uptake of CFZ loaded and mannose functionalized NLCs. Overall, the obtained results indicate that MAN-CFZ NLCs represent a promising strategy to improve the clinical efficacy of CFZ, enabling targeted delivery to macrophages present in cutaneous lesions.
Leprosy is a neglected tropical disease with persistent transmission in endemic regions, where treatment effectiveness is limited by adverse effects and poor patient adherence. Clofazimine (CFZ), a key component of the World Health Organization recommended multidrug therapy, exhibits low aqueous solubility, high tissue accumulation and causes skin pigmentation. To overcome these limitations, this study focused on the development of clofazimine loaded nanostructured lipid carriers functionalized with mannose (MAN-CFZ NLCs) for the local treatment of intracellular infections in dermal macrophages. The NLCs were prepared by hot homogenization, functionalized with mannose to promote macrophage uptake and physicochemically characterized. The in vitro biocompatibility of the formulations was evaluated in fibroblast and macrophage cell lines. Finally, NLC internalization studies were performed in resting (M0) and activated (M1) macrophages. The results showed that the developed nanosystems exhibited a nanometric size of approximately 150 nm, high monodispersity (PDI less than 0.2) and a notable CFZ loading capacity of about 4 percent. Biocompatibility assessment demonstrated good in vitro tolerability of the formulations, while internalization assays revealed enhanced uptake of CFZ loaded and mannose functionalized NLCs. Overall, the obtained results indicate that MAN-CFZ NLCs represent a promising strategy to improve the clinical efficacy of CFZ, enabling targeted delivery to macrophages present in cutaneous lesions.
Direction
LANDIN PEREZ, MARIANA (Tutorships)
ROUCO TABOADA, HELENA (Co-tutorships)
LANDIN PEREZ, MARIANA (Tutorships)
ROUCO TABOADA, HELENA (Co-tutorships)
Court
LOZA GARCIA, MARIA ISABEL (Chairman)
YAÑEZ JATO, MATILDE (Secretary)
CSABA , NOEMI STEFANIA (Member)
LOZA GARCIA, MARIA ISABEL (Chairman)
YAÑEZ JATO, MATILDE (Secretary)
CSABA , NOEMI STEFANIA (Member)