Preparation, Characterization, Pharmacokinetics, and Anti-Idiopathic pulmonary fibrosis activity of Bisdemethoxycurcumin liposomes

Bisdemethoxycurcumin (BDMC) exhibits anti-inflammatory, antioxidant, and antitumor properties. Nonetheless, there is currently no published evidence regarding its efficacy in the management of idiopathic pulmonary fibrosis (IPF). Low solubility in water and reduced bioavailability of BDMC upon oral administration limit its application in the clinics. This study aimed to prepare D-α-tocopherol polyethylene glycol (PEG)-1000-succinate (TPGS)- and 1, 2-distearoyl-sn-glycero-3-phospho-ethanolamine (DSPE)-PEG-modified BDMC-loaded liposomes (BDMC-TPGS-DSPE-PEG-L) using the thin-film dispersion technique. Regarding formulation optimization, we employed single-factor experiments combined with Box-Behnken design (BBD). The physicochemical properties, in vitro release characteristics, and pharmacokinetic profiles of the prepared liposomes were systematically characterized. Furthermore, the anti-fibrotic activity of BDMC-TPGS-DSPE-PEG-L was evaluated in bleomycin (BLM)-induced A549 cells via MTT assay, senescence-associated β-galactosidase (SA-β-Gal) staining, and immunohistochemical analysis of Collagen-I. The optimal formulation showed favorable characteristics, namely particle size (PS), polydispersed index (PDI), zeta potential, encapsulation efficiency (EE%) and drug loading (DL) to be 232.36 ± 3.75 nm, 0.249 ± 0.016, -28.71 ± 0.976 mV, 95.98 ± 0.02%, and 6.84 ± 0.002%, respectively. The liposomal formulation significantly enhanced BDMC oral bioavailability by 1.6-fold compared to free BDMC. The results of the MTT assay confirmed that the cell inhibition rate of the liposome group decreased in a concentration-dependent manner, which was significantly lower compared to free drug group at the same concentration (P < 0.05). Moreover, microscopic observation showed that high-concentration liposome group significantly reduced senescence-associated β-galactosidase (SA-β-Gal) activity and type I collagen (Collagen-I) expression compared to free BDMC. Altogether, BDMC-liposomes could effectively improve the solubility and bioavailability of BDMC, thereby providing a novel therapeutic option for IPF.