Vitamin D3 loaded polycaprolactone nanoparticles enhance the expression of the antimicrobial peptide cathelicidin in macrophages

Tuberculosis (TB), primarily caused by <i>Mycobacterium tuberculosis</i>, remains a global health burden. Current antibiotic treatments are limited by adverse effects, poor adherence, and drug resistance, necessitating new therapeutic approaches. Recent studies highlight the role of vitamin D3 (VD3) in enhancing host immune responses against the mycobacterium <i>via</i> cathelicidin (an antimicrobial peptide) and autophagy activation. In this study, VD3-loaded poly-ƹ-caprolactone (PCL) nanoparticles (NPs) were synthesized to enhance cathelicidin expression in macrophages. NPs containing cholecalciferol, calcifediol, and calcitriol were synthesized using an emulsification solvent-evaporation technique. Average sizes of synthesized NPs ranged from 304.7 to 458.7 nm, with polydispersity index (PDI) and zeta potential (ZP) ranging from 0.103 to 0.257 and −17.3 to −7.47 mV, respectively. Encapsulation efficiencies were 9.68%, 10.99%, and 19.28% for cholecalciferol, calcifediol, and calcitriol, respectively. VD3-encapsulated NPs stimulated a dose-dependent increase in cathelicidin expression in THP-1 macrophages. Encapsulated calcifediol and calcitriol (100 ng/ml) induced the expression of 243.46 ng/ml ± 4.55 ng/ml and 396.67 ng/ml ± 25.24 ng/ml of cathelicidin, respectively, which was significantly higher than that induced by the free drugs. These findings suggest that NP encapsulation may offer a more efficient approach to using vitamin D3 for inducing cathelicidin expression as a host-directed treatment for TB.