查找使用阿拉丁产品的科研文献

Solid self-microemulsifying drug delivery system (S-SMEDDS) prepared by spray drying to improve the oral bioavailability of cinnamaldehyde (CA)

Yun Meng,Ye Cai,Mengyao Cui,Yuhang Xu,Long Wu,Xiang Li,Xiaoqin Chu

The aim of this study was to prepare a solid self-microemulsifying drug delivery system (S-SMEDDS) of cinnamaldehyde (CA) by spray drying technique to improve the oral bioavailability of CA. The preparation of CA S-SMEDDS with maltodextrin as the solid carrier, a core-wall material mass ratio of 1:1, a solid content of 20% (w/v), an inlet air temperature of 150 °C, an injection speed of 5.2 mL/min, and an atomization pressure of 0.1 MPa was determined by using the encapsulation rate as the index of investigation. Differential scanning calorimetry (DSC) revealed the possibility of CA being encapsulated in S-SMEDDS in an amorphous form. The in-vitro release showed that the total amount of CA released by S-SMEDDS was approximately 1.3 times higher than that of the CA suspension. Pharmacokinetic results showed that the relative oral bioavailability of CA S-SMEDDS was also increased to 1.6-fold compared to CA suspension. Additionally, we explored the mechanism of CA uptake and transport of lipid-soluble drugs CA by S-SMEDDS in a Caco-2/HT29 cell co-culture system for the first time. The results showed that CA S-SMEDDS uptake on the co-culture model was mainly an energy-dependent endocytosis mechanism, including lattice protein-mediated endocytosis and vesicle-mediated endocytosis. Transport experiments showed that CA S-SMEDDS significantly increased the permeability of CA in this model. These findings suggested that CA S-SMEDDS is an effective oral solid dosage form for increasing the oral bioavailability of lipid-soluble drug CA.

SMEDDS for improved oral bioavailability and anti-hyperuricemic activity of licochalcone A

Zhongan Zhu,Jing Liu,Yuhang Yang,Michael Adu-Frimpong,Hao Ji,Elmurat Toreniyazov,Qilong Wang,Jiangnan Yu,Ximing Xu

Enhanced oral bioavailability of [6]-Gingerol-SMEDDS: Preparation, in vitro and in vivo evaluation

Yang Xu,Qilong Wang,Yingshu Feng,Caleb Kesse Firempong,Yuan Zhu,Emmanuel Omari-Siaw,Yuanyuan Zheng,Zunqin Pu,Ximing Xu,Jiangnan Yu

The purpose of this study was to develop a [6]-Gingerol-loaded self-microemulsifying drug delivery system ([6]-Gingerol-SMEDDS) for oral administration and enhanced bioavailability of the drug. The [6]-Gingerol-SMEDDS, consisting of oils (ethyl oleate), surfactant (Cremophor EL35) and co-surfactant (1,2-propanediol), showed an acceptable spherical nanoparticle with stable physicochemical properties such as the mean droplet size (73.06 ± 0.49 nm), zeta potential (−2.45 ± 0.41) and encapsulation efficiency (89.40 ± 1.11%). The in vitro release of [6]-Gingerol from the delivery system in the three different media (HCl, pH 1.2; Double distilled water, pH 7.0; phosphate buffer solution, pH 7.4) was significantly higher than in the free drug. The [6]-Gingerol-SMEDDS also exhibited prolonged plasma circulation which led to 6.58-fold increase in oral bioavailability compared with the free drug. These findings indicated that the developed [6]-Gingerol-SMEDDS could be a promising alternative in improving the solubility and oral bioavailability of [6]-Gingerol, as well as increasing its biological applications.

Preparation of a colon-specific sustained-release capsule with curcumin-loaded SMEDDS alginate beads

Yuxia Zhang,Yan Bai,Huali Chen,Yuanrui Huang,Pei Yuan,Liangke Zhang

A colon-specific capsule with alginate beads containing a self-microemulsifying drug delivery system (SMEDDS) was developed and evaluated. The SMEDDS technique was used to improve the solubility of curcumin (Cur). After encapsulating the Cur-loaded SMEDDS, the alginate beads were placed inside an impermeable capsule body. A konjac glucomannan/lactose/hydroxypropyl methylcellulose (KG/Lac/HPMC) plug tablet was then prepared and placed in the mouth of the capsule. The capsule demonstrated a pulsatile drug-release profile with a specific lag time and subsequent sustained-release phase. The lag time was modified by changing the type of HPMC and the ratio of KG/Lac/HPMC. In addition, 0.5% β-mannase solution and 5% rat cecal solution were used to simulate the colon fluid, significantly decreasing the lag time of the capsule. The results show that the capsule has potential for use in colon-specific drug delivery and exhibits a sustained-release characteristic.

Effect of Lipolysis on Drug Release from Self-microemulsifying Drug Delivery Systems (SMEDDS) with Different Core/Shell Drug Location

Zhang Jianbin,Lv Yan,Zhao Shan,Wang Bing,Tan Mingqian,Xie Hongguo,Lv Guojun,Ma Xiaojun

The objective of this study is to investigate the effect of lipolysis on the release of poorly water-soluble drug from SMEDDS in the perspective of drug core/shell location. For this purpose, four SMEDDS formulations with various core/shell properties were developed based on long-chain lipid or medium-chain lipid as well as different surfactant/oil ratios. Poorly water-soluble drugs, hymecromone and resveratrol, were significantly solubilized in all SMEDDS formulations and the diluted microemulsions. Fluorescence spectra analysis indicated that hymecromone was mainly located in the shell of microemulsions, while resveratrol was located in the core. The effect of lipolysis on the release rates of drugs with different core/shell locations were investigated by a modified in vitro drug release model. For the drug located in the shell, hymecromone, the release profiles were not affected during the lipolysis process and no significant differences were observed among four formulations. For the drug located in the core, resveratrol, the release rates were increased to various degrees depending on the extent of digestion. In conclusion, the drug core/shell location plays an important role for determining the effect of lipolysis on drug release from SMEDDS formulation.

Development and optimization of a self micro-emulsifying drug delivery system (SMEDDS) for co-administration of sorafenib and curcumin

Huang Xingzhen,Feng Lizhen,Lu Xuefang,Yang Fan,Liu Shengjun,Wei Xueqian,Huang Jinping,Wang Yao,Huang Dongyi,Huang Tingting

In this study, we developed a novel co-administration of curcumin and sorafenib using a Self micro-emulsifying Drug Delivery System (SMEDDS) called Sorafenib-Curcumin Self micro-emulsifying Drug Delivery System (SOR-CUR-SMEDDS). The formulation was optimized using star point design-response surface methodology, and in vitro cellular experiments were conducted to evaluate the delivery ratio and anti-tumor efficacy of the curcumin and sorafenib combination. The SOR-CUR-SMEDDS exhibited a small size distribution of 13.48 ± 0.61 nm, low polydispersity index (PDI) of 0.228 ± 0.05, and negative zeta potential (ZP) of − 12.4 mV. The half maximal inhibitory concentration (IC 50 ) of the SOR-CUR-SMEDDS was 3-fold lower for curcumin and 5-fold lower for sorafenib against HepG2 cells (human hepatocellular carcinoma cells). Transmission electron microscopy (TEM) and particle size detection confirmed that the SOR-CUR-SMEDDS droplets were uniformly round and within the nano-emulsion particle size range of 10–20 nm. The SMEDDS were characterized then studied for drug release in vitro via dialysis membranes. Curcumin was released more completely in the combined delivery system, showing the largest in vitro drug release (79.20%) within 7 days in the medium, while the cumulative release rate of sorafenib in the release medium was low, reaching 58.96% on the 7 day. In vitro pharmacokinetic study, it demonstrated a significant increase in oral bioavailability of sorafenib (1239.88-fold) and curcumin (3.64-fold) when administered in the SMEDDS. These findings suggest that the SMEDDS formulation can greatly enhance drug solubility, improve drug absorption and prolong circulation in vivo, leading to increased oral bioavailability of sorafenib and curcumin. Graphical abstract

Development of an Orally Bioavailable Isoliquiritigenin Self-Nanoemulsifying Drug Delivery System to Effectively Treat Ovalbumin-Induced Asthma

Mingzhuo Cao,Mengling Zhan,Zheng Wang,Zeqian Wang,Xiu-Min Li,Mingsan Miao

Purpose Isoliquiritigenin (ILQ), an important component of Anti-Asthma Herbal Medicine Intervention (ASHMI), had shown potent anti-asthma effect in vitro in our previous study. However, poor solubility and low bioavailability hindered in vivo application to treat asthma. This study was to develop a novel ILQ loaded self-nanoemulsifying drug delivery system (ILQ-SMEDDS) with enhanced bioavailability. Methods The optimized SMEDDS formulation was composed of ethyl oleate (oil phase), Tween 80 (surfactant) and PEG400 (co-surfactant) at a mass ratio of 3:6:1. The physiochemical properties of ILQ-SMEDDS, including drug content, globule size, zeta potential, scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, were characterized. And the in vitro release profile, in situ intestinal absorption, in vivo pharmacokinetic parameters and the anti-asthma effect of ILQ suspension and ILQ-SMEDDS were evaluated. Results The ILQ-SMEDDS had an average globule size of 20.63 ± 1.95 nm with a polydispersity index (PDI) of 0.11 ± 0.03, and its zeta potential was −12.64 ± 2.12 mV. The cumulative release rate of ILQ from ILQ-SMEDDS to the simulated gastrointestinal tract was significantly higher than that of free ILQ suspension. And area under curve with ILQ-SMEDDS was found to be 3.95 times higher than that of ILQ suspension indicating improved bioavailability by SMEDDS. Although ILQ-SMEDDS showed a slight less effective inhibitory effect on eotaxin-1 in human lung fibroblast (HFL-1) cells than free ILQ, in an ovalbumin-induced asthma model, ILQ-SMEDDS exhibited more efficacy than ILQ suspension in improving asthma-associated inflammation, including eosinophil production, ovalbumin-specific immunoglobulin E (OVA-sIgE), interleukin 4 (IL 4), interleukin 5 (IL 5) and interferon-γ (IFN-γ). Even the low dose of ILQ-SMEDDS group (10 mg/kg) showed better anti-asthma effect than that of the ILQ suspension group (20 mg/kg). Conclusion Compared with ILQ suspension, ILQ-SMEDDS showed significantly improved bioavailability and anti-asthma effect, revealing its potential as a favorable pharmaceutical agent for treating asthma.

Development and Evaluation of a Phospholipid Complex-Loaded SMEDDS for Enhanced Oral Delivery of H007, a Novel Anti-Hyperlipidemic Drug

Chunxi Liu,Lundang Guo,Liqing Chen,Xiaoliang Gong,Zunsheng Han,Jing Feng,Chi Zhang,Song Wu,Qingyun Yang

Background : H007 is a novel selective AMP-activated protein kinase (AMPK) activator with demonstrated efficacy against hyperlipidemia; however, its oral bioavailability is limited by poor solubility and low intestinal permeability. This study aimed to develop a self-microemulsifying drug delivery system (SMEDDS) incorporating a H007–phospholipid complex (H007-PC) to improve both solubility and intestinal permeability. Methods : H007-PC-SME was prepared by integrating phospholipid complexes into an SMEDDS formulation. The formulation was optimized on the basis of emulsification efficiency, droplet size, and zeta potential, and was then evaluated for stability, in vitro drug release, and cellular uptake. Different H007 formulations were orally administered to golden hamsters to assess bioavailability, and a chylomicron flow blockade hamster model was used to evaluate lymphatic transport. Results : The optimized H007-PC-SME showed good stability, rapid self-emulsification, and improved drug solubility. Relative to ordinary H007 tablets, the relative bioavailability of H007-SME and H007-PC-SME was 376.65% and 464.62%, respectively, when calculated from M1 exposure, and 314.01% and 463.55%, respectively, when calculated from MP exposure. When evaluated in a cycloheximide model, H007-SME and H007-PC-SME increased the lymphatic transport fraction of M1 from approximately 0% to 22% and 54%, and that of MP from approximately 1% to 28% and 52% compared with ordinary H007 tablets. Conclusions : H007-PC-SME combines stable phospholipid complex formation with strong self-emulsification performance and effective drug dissolution. By overcoming the intrinsic limitations of the H007 active pharmaceutical ingredient and ordinary H007 tablets, this formulation improves membrane permeability and lymphatic transport, thereby enhancing oral bioavailability and therapeutic potential. The formulation shows good stability and acceptable in vitro biocompatibility under the tested conditions. The preparation process is straightforward, reproducible, and suitable for further pharmaceutical development.

D-α-tocopherol polyethylene glycol 1000 succinate-based microemulsion delivery system: Stability enhancement of physicochemical properties of luteolin

Yimei Zheng,Chengang Zhao,Boyu Chen,Hui Teng,Chao Ai,Lei Chen

In the present study, D-α-Tocopherol polyethylene glycol 1000 succinate-based self-microemulsifying drug delivery systems (TPGS-SMEDDS) were introduced to enhance the solubility and stability of luteolin. The ternary phase diagrams were constructed to obtain the maximum area of microemulsion and suitable formulations of TPGS-SMEDDS. The particle size distribution and polydispersity index of selected TPGS-SMEDDS were analyzed to be less than 100 nm and 0.4, respectively. The thermodynamic stability results suggested that the TPGS-SMEDDS was stable during the heat-cool and freeze–thaw cycle. Moreover, the TPGS-SMEDDS exhibited excellent encapsulation capacity (51.21 ± 4.39 to 85.71 ± 2.40%) and loading efficiency (61.46 ± 5.27 to 102.86 ± 2.88 mg/g) to luteolin. In addition, the TPGS-SMEDDS showed an admirable vitro release ability with a ratio of more than 88.40 ± 1.14% for luteolin in 24 h. Therefore, TPGS-based SMEDDS might provide an effective role for the oral administration of luteolin and holds promise as a potential delivery for poorly soluble bioactive compounds.