European Journal of Pharmaceutics and Biopharmaceutics最新文献

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.

The integration of monoclonal antibodies with liposomal nanocarriers has opened new possibilities in targeted cancer therapy. Immunoliposomes, which are liposomes surface-conjugated with antibodies or antibody fragments, offer dual specificity by combining passive targeting (via the enhanced permeability and retention effect) with active targeting of tumor-specific antigens. This design allows for increased drug accumulation in tumor tissue and reduced off-target toxicity, which are critical challenges in conventional chemotherapy. Although no immunoliposomal therapy has yet received the FDA or EMA approval, the platform continues to evolve. Several formulations are under clinical investigation for various solid tumors, including triple-negative breast cancer, glioblastoma, and non-small cell lung cancer. For example, in a phase II study of anti-EGFR immunoliposomes loaded with doxorubicin in advanced triple-negative breast cancer (NCT02833766), the median progression-free survival was 3.5 months, with 73% of patients experiencing disease progression within the first year. Immunoliposomes hold promise as future therapeutic agents, especially when integrated with molecular diagnostics and patient-specific targeting strategies. However, their clinical translation requires overcoming biological and technological barriers to ensure reproducible efficacy and safety. This review critically examines current progress and explores future perspectives for this emerging therapeutic strategy in precision oncology.

A new generation of pH-responsive magnetic theranostic nanovectors (NV) has been developed to deliver doxorubicin (DOX) to triple negative breast cancer (TNBC) cells which overexpress epidermal growth factor receptor EGFR. DOX was loaded onto functionalized NV using a pH-sensitive DOX-Fe²⁺ complex (hereafter called NV_scFv-DOX). NV_scFv-DOX consists of superparamagnetic iron oxide nanoparticles (SPIONs), labelled with Dylight^TM 680 fluorophore, and coated with a layer of covalently bound polyethylene-glycol (PEG) which is partially functionalized with anti-EGFR scFvs (average ratio is ≈12 scFv per nanovector). The physico-chemical characteristics of the new nanovectors were suitable for IV injection: hydrodynamic diameter D_H below 150 nm, polydispersity index below 0.3 and slightly negative surface charge (≈ -10 mV). Thanks to the functional grafted scFvs, the NV_scFv-DOX were able to recognize the EGFR antigen efficiently. Using preformed DOX-Fe²⁺ complex which binds to the SPION surface in a pH-dependent manner, about 6.5% w/w (DOX/iron oxide) of the drug were loaded onto the NV_scFv-DOX. The drug loading and release in its native form at acidic pH were characterized by surface-enhanced Raman scattering (SERS) spectroscopy. The dual fluorescent response of both Dylight^TM680 and that of DOX was confirmed, which is promising for theranostic use of the nanovectors. Finally, the in vitro toxicity of NV_scFv-DOX on the EGFR-overexpressing TNBC cell line MDA-MB-468 was confirmed and compared to that of free DOX and NV_scFv without DOX. Together, all these properties of the NV_scFv-DOX are promising for their potential use as theranostic platform for TNBC treatment.

This study systematically integrated critical material attributes (CMAs) influencing drug release, focusing on factors such as particle size and excipient composition, and characterization of polymorphic form. As a model compound, a BCS class II drug Telmisartan was selected, and the methodology was evaluated using seven different formulations of Telmisartan through comprehensive analysis. The orthogonal analytical techniques, including chromatography, hot-stage microscopy, NMR spectroscopy, and dissolution testing were employed for evaluating critical quality attributes (CQAs). Systematic efforts were made to develop a biopredictive dissolution method using USP dissolution Apparatus I, II, and IV. Based on the t_max value of telmisartan, a multi-stage dissolution strategy was developed to understand the behaviour of formulation in acidic and neutral pH corresponding to the stomach and duodenum under fasting conditions. After de-formulation experiments, formulations were categorized into different buckets based on the size of API particles (d-90 value of 8 ± 2 µm; 12 ± 2 µm and >15 µm), the type of excipients present (functional excipient and non-functional excipients), and the micro-environmental pH of the formulations. A rank-based approach was applied to evaluate a robust framework for understanding the differences between these generic formulations. This approach not only supports comprehensive formulation development through CMA-CQA correlations, but also aligns with regulatory expectations for adopting multi-dissolution methods as in vitro testing in cases of formulation change requirements with a bio-equivalance waiver for post-approval formulation changes.

Quercetin has antioxidant, anti-inflammatory, antibacterial, and anticancer effects. However, its therapeutic efficacy is limited by poor water solubility, low oral absorption, and limited bioavailability. In this study, a novel deep eutectic solvent (DES) in water (DES/W) microemulsion system was developed, wherein the DES was composed of DL-menthol and capric acid at a molar ratio of 7:3, to simultaneously accomplish enhanced quercetin solubilization and promoted mucosal permeation, both of which ensuring an adequate oral bioavailability and sufficient therapeutic effectiveness. Optimized DESs were used with microfluidic technology to create uniform quercetin-loaded DES/W microemulsions under the optimal formulation conditions: Tween 20 as the surfactant, a surfactant concentration of 1.37%, a continuous phase flow rate of 30.98 mL/h, and a dispersed phase flow rate of 3.15 mL/h. The results showed that the obtained microemulsions increased quercetin solubility, retention time in the intestines, and mucosal absorption, improving drug absorption and bioavailability. Pharmacokinetic studies showed that compared with free quercetin, the area under the plasma concentration-time curve (AUC_0～t) and maximum plasma concentration (C_max) of the microemulsion formulation were significantly increased, with AUC_0～t being 5.54-fold higher than that of free quercetin. Notably, the use of microfluidic technology in preparing these microemulsions considerably reduces the need for surfactants, thus enhancing the biosafety of DES-based microemulsions. Overall, the DES/W microemulsions prepared by microfluidics could effectively addresses the challenges associated with poor absorption and low bioavailability of insoluble drugs with highly monodisperse and uniform formulations.