INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Li-Jing Lan,Lian-Bing Long,Ling-Zhi Shi,Ming-Wei Huo,Xiang-Xiang Huang,Ya-Wen Liu,Le-Yan Gu,Jing-Yi Liu,Ye-Chao Zhang,Renyu Huang,Qing-Ri Cao
The industrial scalability and clinical translation of liposomal formulations are significantly hindered by challenges in stability and batch-to-batch variability. To address these limitations, docetaxel (DTX)-loaded long-circulating liposomal freeze-dried powders were engineered via a synergistic integration of microfluidic technology and lyophilization, optimized through an orthogonal experimental design focusing on particle size, polydispersity index (PDI), and entrapment efficiency (EE). The optimized formulation, incorporating hydroxypropyl-β-cyclodextrin (HP-β-CD) as a lyoprotectant, demonstrated nanoscale particle diameter (∼120 nm), monodisperse distribution (PDI < 0.2), and elevated EE (>90 %), with physicochemical integrity preserved post-lyophilization. Reconstituted DTX liposomes (DTX-Lip) exhibited pH-dependent sustained release kinetics, with enhanced drug elution at acidic pH (5.5) versus physiological pH (7.4). Solid-state characterization (XRD, FT-IR, DSC) confirmed molecular interactions between DTX and lipid-excipient matrices. In vitro cytotoxicity assays revealed superior apoptotic induction in A549 human lung carcinoma cells by DTX-Lip compared to free DTX solution (DTX-Sol). Pharmacokinetic profiling in vivo demonstrated prolonged systemic circulation of DTX-Lip, marked by significantly elevated area under the curve (AUC 0-∞ ), maximum drug concentration (C max ), mean retention time (MRT 0-∞ ), longer half-life (T 1/2 ), lower clearance (CL) and steady-state volume of distribution (V ss ) relative to DTX-Sol (p < 0.05). In a C57BL/6 murine lung cancer model, DTX-Lip elicited significant tumor suppression (p < 0.05) without mortality, underscoring enhanced therapeutic efficacy and mitigated systemic toxicity. Collectively, the engineered DTX-Lip system combines optimal nano-pharmaceutical attributes (size, homogeneity, EE), controlled release, and favorable in vitro-in vivo performance, offering a robust platform for industrial-scale production of stable, efficacious liposomal DTX formulations. These findings advance translational strategies for liposome-based chemotherapeutics with improved reproducibility and clinical safety.
研究领域:
肿瘤学
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药剂学
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纳米医学
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药物递送
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药代动力学
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转化医学
·
临床药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Science & Nutrition
·
2025
·Vol. 13
·期 10
·e71000
·
IF 3.8
Zhou Ning,Chen Linlin,Zhang Xing,He Kunmiao,Xu Tiantian,Wang Hanshuo,Sun Jie,Yu Miao,Ren Hongtao,Wang Na
Proanthocyanidins play a crucial role in celiac disease (CD) through their antioxidant and anti-inflammatory properties, effectively regulating oxidative stress and inflammatory responses. However, the poor stability and low bioavailability of proanthocyanidins significantly limit their therapeutic applications. The aim of this study was to investigate the effects of lyoprotectants on proanthocyanidin nanoliposome freeze-dried powder (PCNL-FD), characterize its structural properties, evaluate its in vitro antioxidant capacity and explore its protective effects in a celiac disease cell model. The addition of 4% trehalose as a lyoprotectant effectively maintained the encapsulation efficiency and redispersion stability of PCNL-FD. FTIR and TEM analyses confirmed the successful incorporation of proanthocyanidins into the phospholipid bilayer. In vitro antioxidant assays showed that PCNL-FD exhibited significantly higher DPPH, ABTS, and hydroxyl radical scavenging activities compared to free proanthocyanidins. In the p31-43 peptide-induced celiac disease Caco-2 cell model, PCNL-FD significantly reduced oxidative stress by decreasing ROS and MDA levels while increasing GSH levels and antioxidant enzyme activities (SOD and CAT). The formulation showed anti-inflammatory effects by inhibiting pro-inflammatory cytokines (TNF-α, IL-6) and promoting anti-inflammatory cytokines (IL-4, IL-10). In addition, PCNL-FD activated the Keap1/Nrf2 signaling pathway and upregulated the expression of NQO-1 and HO-1. This nanoliposomal delivery system effectively overcame the bioavailability and stability limitations of free proanthocyanidins, providing new insights into the management of oxidative stress in inflammatory diseases such as celiac disease.
研究领域:
分子生物学
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药剂学
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免疫学
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消化病学
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营养学
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纳米医学
·
氧化应激
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2017
·Vol. 19
·期 2
·541-550
·
IF 2.451
Liu Daichun,Galvanin Federico,Yu Ying
The purpose of this study was to prepare ginkgolide B (GB) lyophilized powder for injection with excellent appearance and stable quality through a formulation screening and by optimizing the freeze-drying process. Cremophor EL as a solubilizer, PEG 400 as a latent solvent, and mannitol as an excipient were mixed to increase the solubility of GB in water to more than 18 times (about from 2.5 × 10 −4 mol/L (0.106 mg/mL) to 1.914 mg/mL). Formulation screening was conducted by orthogonal design where the content of GB in the solution before lyophilization (using external standard method of HPLC) and reconstitution time after lyophilization were the two evaluation indexes. The optimized formulations were GB in an amount of 2 mg/mL, Cremophor EL in an amount of 16% ( v / v ), PEG 400 in an amount of 9% ( v / v ), mannitol in an amount of 8% ( w / v ), and the solution pH of 6.5. Through four single-factor experiments (GB adding order, preparation temperature of GB solution, adding amount, and adsorption time of activated carbon), the preparation process of GB solution was confirmed. The glass transition temperature of maximally GB freeze-concentrated solution was − 17.6°C through the electric resistance method. GB lyophilized powder began to collapse at − 14.0°C, and the fully collapsed temperature was − 13.0°C, which were determined by freeze-drying microscope. When the collapse temperature was determined, the primary drying temperature was obtained. Thereby, the freeze-drying curve of GB lyophilized powder was initially identified. The freeze-drying process was optimized by orthogonal design, the qualified product appearance and residual moisture content were the two evaluation indexes. The optimized process parameters and process were (1) shelf temperature, decreased from room temperature to − 45.0°C, at 0.5°C/min in 2 h; (2) shelf temperature increased from − 45.0 to − 25.0°C, at 0.1°C/min, maintained for 3 h, and the chamber pressure was held at 10 Pa; (3) shelf temperature was increased from − 25.0 to − 15.0°C at 0.1 °C/min, maintained for 4 h, and the chamber pressure was held at 10 Pa; and (4) shelf temperature was increased from − 15.0 to 20.0°C at 1.0 °C/min, maintained for 4 h, and the chamber pressure was raised up to 80 Pa. In these lyophilization process conditions, the products complied with relevant provisions of the lyophilized powders for injection. Meanwhile, the reproducibility was satisfactory. Post-freezing annealing had no significantly beneficial effects on shortening the freeze-drying cycle and improving the quality of GB lyophilized powder.
研究领域:
药学
·
药剂学
·
药物传递系统
·
制药技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）