Posted by /The biological properties of pβCD of different molecular weights were studied. Strikingly, only the low-molecular-weight pβCD (LMW-pβCD) displayed antibacterial activity, in contrast to the high-molecular-weight one. Mechanistically, this activity was linked to the inhibition of Mycobacterium tuberculosis entry into macrophages through disruption of lipid rafts. Transcriptomic profiling further revealed that the LMW-pβCD also enhanced pro-inflammatory cytokine secretion, suggesting dual antimicrobial and immunomodulatory functions. Notably, linezolid, an important second-line anti-tuberculosis drug, was efficiently incorporated in pβCD, regardless of its molecular weight. These findings emphasize the critical importance of molecular weight in dictating pβCD bioactivity. Only LMW-pβCD combines antimicrobial and immunomodulatory activities with effective drug delivery, making it a promising candidate for the development of novel anti-tuberculosis therapies.
Altogether, this study highlights that molecular weight is a critical but previously overlooked parameter in the design of CD-based nanomedicines, and points to the LMW-pβCD fraction as a promising candidate for the development of next-generation inhalable formulations against tuberculosis.
Amine Pochet, Jesus Alfredo Godinez-Leon, Axelle Grandé, Tahmida Shamsuddin, Priscille Brodin, Ruxandra Gref, Arnaud Machelart (2026) Dual activity of low-molecular-weight polymeric β-cyclodextrins against tuberculosis. International Journal of Pharmaceutics 688, 126448.
https://doi.org/10.1016/j.ijpharm.2025.126448