RSC Advances
·
2017
·Vol. 7
·期 32
·19815-19827
·
IF 3.108
Liya Zeng,Xin Xin,Yalin Zhang
Nanoemulsions have attracted much attention due to their wide application in commercial industries such as pharmaceutics, food, beverages and skin care. Cremophor EL has been extensively used for emulsification, protection and solubilization of various lipophilic bioactive agents. However, their anaphylactoid hypersensitivity reactions are still challenging. Therefore, the aim of this study was to develop and characterize a promising, low-level Cremophor EL-stabilized o/w nanoemulsion using the spontaneous emulsification method for oral administration. From comparing the physicochemical properties (particle size and size distribution) of their emulsions, Cremophor has better emulsifying capacity than Tween and the droplet radius of emulsions can be reduced by increasing the surfactant concentration in current systems. The impact of various short-chain alcohols (C–OH < 5) on the formation and stability of nanoemulsions was also investigated to optimize the formulations. And there is a good correlation between nanoemulsion droplet size and the surfactant packing parameter (p). The smallest droplet size with the narrowest size distribution was produced by the system containing ethylene glycol as a cosurfactant. However, preparation of nanoemulsions with ethylene glycol was a time-consuming process since it was difficult to emulsify the water-induced gel-structure. Surfactant-to-oil mass ratio and surfactant-to-cosurfactant levels had to be optimized to produce fine droplets. Moreover, there was a linear relationship between the viscosity/log P value of alcohols and droplet size. Ostwald ripening was the dominant breakdown process of nanoemulsions obtained in the ethyl oleate/Cremophor EL–butanol (3 : 2)/water system. Ostwald ripening rate was increased with increasing surfactant concentration. Dilution (100×) of this system considerably improved their stability against droplet growth. This study demonstrated that alcohol addition might be a useful tool for preparing Cremophor EL-stabilized nanoemulsions for pharmaceutical applications.
研究领域:
药剂学
·
化学工程
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2019
·
IF 3.973
Yi Zhang,Haijie Zhao,Xiaozhen Wang,Hehan Xiao,Yanqing Guan
Microemulsions have attracted great interest in the biomedical field involving drug delivery, skin treatment and immune-adjuvant. In any case, microemulsions administered in vivo will more or less contact blood tissue inevitably, however there is no specialized investigation on the interaction between microemulsions and human blood components at cellular and membrane levels. Herein we investigate the effect of a typical microemulsion formulation (Cremophor EL/ethanol/oleinic acid/water (CEOW-ME)) with different extent dilution on human blood components (red blood cells (RBCs), coagulation factor, plasma albumin) and blood coagulation function. It was found that CEOW-ME had a concentration dependent effect on blood components and displayed anti-coagulant activity, causing coagulation factor activation, platelet aggregation impairment and RBC morphology alteration, whereas no impacting on fibrinogen polymerization. Interestingly CEOW-ME had greater influence on the coagulation factors in the plasma related to intrinsic coagulation pathway than extrinsic coagulation pathway. Additionally, spectroscopy studies (DLS, UV–vis, Fluorescence and CD) demonstrated that the impact of CEOW-ME on the size, local micro-structure and conformation of albumin was mediated by hydrophobic binding-induced unfolding and disordering of hierarchical albumin structure. These findings give more comprehensive information for forecasting the potential interaction of the in vivo -administered microemulsions with the cells and bioactive molecules in the human blood.
研究领域:
药理学
·
生物医学工程
·
血液学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2024
·
IF 2.8
Sigfridsson Kalle,Zhang Xiang,Llinas Antonio
ObjectivesThe objective of the present case study was to increase the exposure of the poorly soluble crystalline compound A.MethodsMice received 10 mg/kg of crystalline compound A formulated in eight different cosolvent, oil, and cyclodextrin mixtures.Key findingsIn all cases, AUC0–24h and maximum blood/plasma concentration (Cmax) were in the range of 6–16 µM × h and <1.4 µm, respectively, with a bioavailability below 18%. When 6% cremophor (CrEL) was added to three selected vehicles, AUC0–24h and Cmax increased ~5–10 times. The obtained pharmacokinetic profile of the most improved formulation using CrEL was possible to superimpose on the one obtained after administration of a CrEL-free amorphous solid dispersion (ASD, HPMC-AS:drug, 80:20) suspension of compound A.ConclusionsIt is crucial to find an optimal screen vehicle as early as possible for a poorly water-soluble lead series and then avoid time and resource-consuming vehicle testing of multiple compounds in vivo. An ASD approach is more suited for clinical development when more time and resources are allocated to the project. In this case study, some preclinical formulations were used to maximize exposure but also as preindicators for ASDs later in the development chain.
研究领域:
药理学
·
药物开发
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2016
·
IF 2.76
Liya Zeng,Yalin Zhang
The principles of formation and stability of nano-emulsions have been extensively investigated in previous research. In this study, we focus on the impact of short-chain alcohols (C < 5) on the formation and stability of oil-in-water nano-emulsions prepared by the spontaneous emulsification method. Due to its smaller droplet size and excellent optical transparency, the nano-emulsion stabilized by Cremophor EL was selected for further study. Addition of alcohol facilitated the nano-emulsion formation, moreover, the droplet size decreased with increasing alcohol chain length (C > 2) and hydroxyl groups. Nevertheless, the droplet size then increased further with the addition of alcohols, which we ascribed to the effect of alcohols on droplet flocculation. An optimum Cremophor EL-to-1-butanol ratio of 2:1 was employed to construct the ternary phase diagram. It was found that the fine droplets (r < 100 nm, PDI < 0.2) were obtained only when converting the initial oil drops completely into the lamellar liquid crystalline phase and/or bicontinuous phase and then this phase became supersaturated in oil, so that the nucleation of oil drops occurred spontaneously. According to the dynamic light scattering results, coalescence and Ostwald ripening were the main destabilization mechanisms in our systems. Notably, nano-emulsion stability was greatly improved with ethanol in comparison to 1-propanol and 1-butanol.
研究领域:
化学工程
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2016
·
IF 3.994
Tianpeng Zhang,Dong Dong,Danyi Lu,Shuai Wang,Baojian Wu
Oral emodin , a natural anthraquinone and active component of many herbal medicines, is poorly bioavailable because of extensive first-pass glucuronidation. Here we aimed to prepare emodin nanoemulsion (EMO-NE) containing cremophor EL , and to assess its potential for enhancing transcellular absorption of emodin using UGT1A1-overexpressing MDCKII cells (or MDCK1A1 cells). EMO-NE was prepared using a modified emulsification technique and subsequently characterized by particle size, morphology, stability, and drug release. MDCKII cells were stably transfected with UGT1A1 using the lentiviral transfection approach. Emodin transport and metabolism were evaluated in Transwell-cultured MDCK1A1 cells after apical dosing of EMO-NE or control solution. The obtained EMO-NE (116 ± 6.5 nm) was spherical and stable for at least 2 months. Emodin release in vitro was a passive diffusion-driven process. EMO-NE administration increased the apparent permeability of emodin by a 2.3-fold ( p < 0.001) compared to the pure emodin solution (1.2 × 10 −5 cm/s vs 5.3 × 10 −6 cm/s). Further, both apical and basolateral excretion of emodin glucuronide (EMO-G) were significantly decreased (≥ 56.5%, p < 0.001) in EMO-NE group. This was accompanied by a marked reduction (57.4%, p < 0.001) in total emodin glucuronidation. It was found that the reduced glucuronidation was due to inhibition of cellular metabolism by cremophor EL. Cremophor EL inhibited UGT1A1-mediated glucuronidation of emodin using the mixed-type inhibition mechanism. In conclusion, cremophor EL-based nanoemulsion greatly enhanced transcellular permeation of emodin through inhibition of UGT metabolism. This cremophor EL-based nanoformulation may be a promising strategy to improve the oral bioavailability of emodin.
研究领域:
药理学
·
药物递送系统
·
细胞生物学
✓ 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）