查找使用阿拉丁产品的科研文献

Preparation and pharmacodynamic evaluation of isorhamnetin-Soluplus-TPGS mixed micelles

Li Tingyuan,Li Jiaying,Wang Qilong,Gong Mingjie,Wang Xiaowen,Jiang Xia,Hua Qinyang,Ji Hao,Toreniyazov Elmurat,Yu Jiangnan,Cao Xia,Adu-Frimpong Michael,Xu Ximing

Isorhamnetin (ISO) is a kind of flavonoid widely found in sea buckthorn, ginkgo biloba, and other plants. It has many pharmacological activities, but poor solubility in aqueous media has limited its clinical application. In order to increase the bioavailability of ISO, we employed a thin film dispersion method to prepare ISO-loaded Soluplus-TPGS mixed polymer micelle (ISO-STM) and subsequently conducted appropriate characterizations. The micelles prepared in this work were spherical nanoparticles with uniform distribution with respective particle size (PS) and dispersion coefficient (PDI) of 81.62 ± 1.23 nm and 0.115 ± 0.020. Meanwhile, the encapsulation rate (EE) was 91.37% ± 0.82%, whereas the drug loading (DL) was 5.91% ± 0.06%. Compared to free ISO, the dissolution rate of mixed micelles (MM) significantly increased in three media. After oral administration, the oral bioavailability of MM was nearly 3 times higher than free ISO’s. In addition, the results of the zebrafish experiment showed that the anti-aging of zebrafish in the administration group was significantly better than that in the model control group. In summary, ISO-STM is a promising method with the potential to improve the solubility, and bioavailability and enhance the clinical application value of ISO.

TPGS/soluplus® blended micelles: an effective strategy for improving loading capacity of ferroptosis inducer erastin

Junwei Liu,Meihong Zhang,Chuanbin Wu,Xin Pan,Zhengwei Huang

Erastin is the most classical small molecular ferroptosis inducer but its clinical application is hindered due to its poor solubility. Nanotechnology has been used to improve ferroptosis inducer erastin’s solubility. The recently reported erastin-incorporated nanosystems (e.g., nanoparticulate ferritin, poly(ethylene glycol) methyl ether-blockpoly(lactide-co-glycolide) (mPEG-PLGA) nanoparticle, exosome, and liposome) could to some degree elevate its solubility, but were still poor in loading capacity. To be specific, the maximum entrapment efficiency and drug loading in previous studies were approximately 36% and 3.7%, respectively. In order to improve drug loading capacity, we constructed a novel carrier based on Vitamin E d-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®) blended micelles. The erastin@TPGS/Soluplus® micelles were prepared by thin film hydration method, and formulation details including dosage of Soluplus®, the weight ratio of TPGS to Soluplus®, the weight ratio of erastin to TPGS/Soluplus® were optimized. The physicochemical properties of the erastin micelles were measured by DLS, TEM, FTIR, and TG-DSC analysis. The products exhibited a nanoscale and uniform particle size (78.11 ± 0.54 nm) and neutral surface charge (-0.43 ± 0.32 mV). Significantly improved entrapment efficiency (89.63 ± 1.81%) and drug loading rate (10.03 ± 0.14%) were obtained, which was over 2-fold of current reports. The in vitro release study demonstrated that erastin could release in a sustained yet complete manner, and the drug release might be governed by multiple mechanisms including anomalous diffusion of non-Fickian diffusion, matrix erosion and sustained release. In summary, this proposed erastin nanosystem provides a new strategy for improving loading capacity, and may probably augment ferroptosis-inducing therapy for cancer treatment.

Pterostilbene-Loaded Soluplus/Poloxamer 188 Mixed Micelles for Protection against Acetaminophen-Induced Acute Liver Injury

Kehong Dong,Mei Zhang,Ying Liu,Xintao Gao,Xiaochen Wu,Dayong Shi,Chuanlong Guo,Jing Wang

Excessive acetaminophen (APAP) induces excess reactive oxygen species (ROS), leading to liver damage. Pterostilbene (PTE) has excellent antioxidant and anti-inflammatory activities, but poor solubility limits its biological activity. In this study, we prepared PTE-loaded Soluplus/poloxamer 188 mixed micelles (PTE-MMs), and the protective mechanism against APAP-induced liver injury was investigated. In vitro results showed that PTE-MMs protected H2O2-induced HepG2 cell proliferation inhibition, ROS accumulation, and mitochondrial membrane potential destruction. Immunofluorescence results indicated that PTE-MMs significantly inhibited H2O2-induced DNA damage and cGAS-STING pathway activation. For in vivo protection studies, PTE-MMs (25 and 50 mg/kg) were administered orally for 5 days, followed by APAP (300 mg/kg). The results showed that APAP significantly induced injury in liver histopathology as well as an increase in serum aspartate aminotransferase and alanine aminotransferase levels. Moreover, the above characteristics of APAP-induced acute liver injury were inhibited by PTE-MMs. In addition, APAP-induced changes in the activities of antioxidant enzymes such as SOD and GSH in liver tissue were also inhibited by PTE-MMs. Immunohistochemical results showed that PTE-MMs inhibited APAP-induced DNA damage and cGAS-STING pathway activation in liver tissues. For in vivo therapeutic effect study, mice were first given APAP (300 mg/kg), followed by oral administration of PTE-MMs (50 mg/kg) for 3 days. The results showed that PTE-MMs exhibited promising therapeutic effects on APAP-induced acute liver injury. In conclusion, our study shows that the Soluplus/poloxamer 188 MM system has the potential to enhance the biological activity of PTE in the protection and therapeutic of liver injury.

On the inherent properties of Soluplus and its application in ibuprofen solid dispersions generated by microwave-quench cooling technology

Nian-Qiu Shi,Hong-Wei Lai,Yong Zhang,Bo Feng,Xiao Xiao,Hong-Mei Zhang,Zheng-Qiang Li,Xian-Rong Qi

Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, or Soluplus®, is a relatively new copolymer and a promising carrier of amorphous solid dispersions. Knowledge on the inherent properties of Soluplus® (e.g. cloud points, critical micelle concentrations, and viscosity) in different conditions is relatively inadequate, and the application characteristics of Soluplus®-based solid dispersions made by microwave methods still need to be clarified. In the present investigation, the inherent properties of a Soluplus® carrier, including cloud points, critical micelle concentrations, and viscosity, were explored in different media and in altered conditions. Ibuprofen, a BCS class II non-steroidal anti-inflammatory drug, was selected to develop Soluplus®-based amorphous solid dispersions using the microwave-quench cooling (MQC) method. Scanning electronic microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Raman spectroscopy (RS), and Fourier transform infrared spectroscopy (FT-IR) were adopted to analyze amorphous properties and molecular interactions in ibuprofen/Soluplus® amorphous solid dispersions generated by MQC. Dissolution, dissolution extension, phase solubility, equilibrium solubility, and supersaturated crystallization inhibiting experiments were performed to elucidate the effects of Soluplus® on ibuprofen in solid dispersions. This research provides valuable information on the inherent properties of Soluplus® and presents a basic understanding of Soluplus® as a carrier of amorphous solid dispersions.

Preparation and evaluation of astaxanthin-loaded 2-hydroxypropyl-beta-cyclodextrin and Soluplus® nanoparticles based on electrospray technology

Yuanyuan Xue,Youwu Liao,Haiqiao Wang,Shuang Li,Zhengqing Gu,Michael Adu-Frimpong,Jiangnan Yu,Ximing Xu,Hugh D. C Smyth,Yuan Zhu

BACKGROUND Astaxanthin is a type of food-derived active ingredient with antioxidant, antidiabetic and non-toxicity functions, but its poor solubility and low bioavailability hinder further application in food industry. In the present study, through inclusion technologies, micellar solubilization and electrospray techniques, we prepared astaxanthin nanoparticles before optimizing the formulation to regulate the physical and chemical properties of micelles. We accomplished the preparation of astaxanthin nanoparticle delivery system based on single needle electrospray technology through use of 2-hydroxypropyl-β-cyclodextrin and Soluplus® to improveme the release behavior of the nanocarrier. RESULTS Through this experiment, we successfully prepared astaxanthin nanoparticles with a particle size of approximately 80 nm, which was further verified with scanning electron microscopy and transmission electron microscopy. Furthermore, the encapsulation of astaxanthin molecules into the carrier nanoparticles was verified via the results of attenuated total reflectance intensity and X-ray powder diffraction techniques. The in vitro release behavior of astaxanthin nanoparticles was different in media that contained 0.5% Tween 80 (pH 1.2, 4.5 and 6.8) buffer solution and distilled water. Also, we carried out a pharmacokinetic study of astaxanthin nanoparticles, in which it was observed that astaxanthin nanoparticle showed an effect of immediate release and significant improved bioavailability. CONCLUSION 2-hydroxypropyl-β-cyclodextrin and Soluplus® were used in the present study as a hydrophilic nanocarrier that could provide a simple way of encapsulating natural function food with repsect to improving the solubility and bioavailability of poorly water-soluble ingredients. © 2023 Society of Chemical Industry.

Enhancement of oral bioavailability and anti-hyperuricemic activity of aloe emodin via novel Soluplus®—glycyrrhizic acid mixed micelle system

Shi Feng,Chen Lin,Wang Yaping,Liu Jing,Adu-Frimpong Michael,Ji Hao,Toreniyazov Elmurat,Wang Qilong,Yu Jiangnan,Xu Ximing

The objective of this study was to fabricate a novel drug delivery system using Soluplus® (polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer) and glycyrrhizic acid to improve solubility, bioavailability, and anti-hyperuricemic activity of aloe emodin (AE). The AE-loaded mixed micelles (AE-M) were prepared by thin-film hydration method. The optimal AE-M contained small-sized (30.13 ± 1.34 nm) particles with high encapsulation efficiency (m/m, %) of 90.3 ± 1.08%. The release rate of AE increased in the micellar formulation than that of free AE in the four media (DDW, pH 7.0; phosphate buffer solution, pH 7.4; phosphate buffer solution, pH 6.8; and hydrochloric acid aqueous solution, pH 1.2). In comparison to free AE, the pharmacokinetic study of AE-M showed that its relative oral bioavailability increased by 3.09 times, indicating that mixed micelles may promote gastrointestinal absorption. More importantly, AE-M effectively reduced uric acid level by inhibiting xanthine oxidase (XOD) activity in model rats. The degree of ankle swelling, serum levels of interleukin (IL)-1, and IL-6-related inflammatory factors levels all decreased in the gouty arthritis model established via monosodium urate (MSU) crystals. Taken together, the AE-M demonstrated the potential to improve the bioavailability, anti-hyperuricemic activity, and anti-inflammation of AE. Graphical abstract

Impact of hypromellose acetate succinate and Soluplus® on the performance of β-carotene solid dispersions with the aid of sorbitan monolaurate: In vitro-in vivo comparative assessment

Yinglan Li,Jie Xu,Qingran Guan,Huaizhen Zhang,Zhuang Ding,Qingpeng Wang,Zhengping Wang,Jun Han,Min Liu,Yanna Zhao

Solid dispersions (SDs) possess the potential to enhance the bioavailability of insoluble active pharmaceutical ingredients (APIs) by effectively converting them into amorphous state. However, SDs have a tendency to recrystallize unless appropriate excipients are employed. The objective of this study was to evaluate the ability of hypromellose acetate succinate HF (HPMCAS-HF) and Soluplus® to inhibit the recrystallization of β-carotene and improve its in vivo bioavailability through the fabrication of ternary β-carotene solid dispersions (SDs) with the aid of specific surfactant. Due to rapid micellization , the dissolution profiles of β-carotene SDs based on HPMCAS-HF/Span 20 (5:5, w/w) or Soluplus®/Span 20 (6:4, w/w) combinations exhibited significant improvement, which were almost 7–10 times higher than β-carotene bulk powder. DSC and PXRD analysis indicated a notable reduction in the crystallinity degree of β-carotene within the SDs. The stability study demonstrated a half-life of β-carotene in the SDs exceeding 30 days. Additionally, the in vivo pharmacokinetics analysis confirmed that the cellulose derivatives/surfactant combinations significantly enhanced the bioavailability of β-carotene by 1.37-fold and 2.3-fold, respectively. Notably, the HPMCAS-HF/Span 20 combination exhibited superior performance. Consequently, the HPMCAS-HF/Span 20 combination held potential for the advancement of an effective drug delivery system for β-carotene.

Astragaloside-Soluplus/TPGS/glycyrrhizic acid ammonium salt mixed micelles: preparation and pharmacodynamic evaluation

Hong Chen,Michael Adu-Frimpong,Lili Yuan,Yaping Yang,Jollibekov Berdiyar,Jiangnan Yu,Xia Cao,Qilong Wang,Ximing Xu

Astragaloside, a natural flavonol glycoside isolated from plants, exhibits significant tumour-suppressive activity. However, its low solubility and poor bioavailability have hindered its practical application. To improve its bioavailability and therapeutic efficacy, this study prepared Ast-loaded Soluplus/TPGS/Gas hybrid polymer micelles (Ast-STG-M) via the thin-film hydration method. The resulting Ast-STG-M nanoparticles were spherical and uniformly dispersed, characterised by a small particle size (50.92 ± 0.13 nm) and a high encapsulation efficiency (95.24 ± 0.53%). In vitro release profiles demonstrated that the cumulative release rate of Ast from Ast-STG-M was higher than that of free Ast under various pH conditions. After oral administration, compared with free Ast, Ast-STG-M exhibited delayed in vivo elimination and significantly increased bioavailability. Furthermore, results from in vitro and in vivo anti-tumour studies indicated that Ast-STG-M could significantly inhibit the viability of TPC-1 cells, thereby effectively suppressing the growth of solid tumours. In conclusion, Ast-STG-M holds substantial potential as a delivery system for Ast to tumour sites, which not only enhances the oral bioavailability of Ast but also strengthens its anti-cancer activity.

Stabilizing Effect of Soluplus on Erlotinib Metastable Crystal Form in Microparticles and Amorphous Solid Dispersions

Shuyu Jia,Shangqi Ning,Yuting Leng,Qiufang Jing,Zhongyu Xu,Fuzheng Ren

Microparticles (MPs) and amorphous solid dispersions (SDs) are effective methods to improve the dissolution of insoluble drugs. However, stability is a concern for these two high-energy systems, resulting from high surface area and amorphous polymorph, respectively. As an amphiphilic polymer, Soluplus (SOL) is usually used as a carrier in SDs. In this study, erlotinib microparticles (ERL MPs) and erlotinib solid dispersions (ERL SDs) were prepared with SOL by bottom-up technology and solvent evaporation. The solid-state properties of ERL MPs and ERL SDs were characterized by Differential Scanning Calorimetry (DSC), Powder X-Ray Diffraction (PXRD) and Scanning Electron Microscopy (SEM). The ERL MPs existed in a metastable crystal form A while the ERL SDs existed in an amorphous state. Fourier transform infrared spectroscopy (FT-IR) showed that there was a hydrogen bond interaction between the N-H group of ERL and the carbonyl group of SOL in ERL MPs and SDs. The dissolution profiles of ERL SDs and ERL MPs were improved significantly. ERL MPs showed better stability than ERL SDs in accelerated stability test. The discrepant stabilizing effects of polymer SOL in two systems may provide effective ideas for solubilization of insoluble drugs and the stability of drugs after recrystallization.Keywords:erlotinib;soluplus;microparticles;solid dispersions;stabilization

Developing Soluplus®-Based Microparticle Amorphous Solid Dispersions with High Drug Loading for Enhanced Celecoxib Dissolution via Electrospraying

Fan Fan,Zhou Feng,Zhang Jiayu,Yang Junhui,Zhuang Kai,Shan Yudong,Jiang Lei,Zhang Jiantao

Amorphous solid dispersion (ASD) is one of the most studied strategies for improving the dissolution performance of poorly water-soluble drugs, but ASDs often have low drug loadings, thereby necessitating larger dosage sizes. This study intended to create Soluplus® (SOL)-based microparticle ASDs with high drug loading (up to 60 w/w%) and long-term stability (at least 16 months) using electrospraying to enhance the dissolution of poorly water-soluble celecoxib (CEL). X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analyses showed that the electrosprayed SOL-CEL microparticles were amorphous, and Fourier transform infrared spectroscopy (FTIR) data indicated the presence of hydrogen bonding between SOL and CEL in the microparticles, which helped stabilize the ASDs. In vitro dissolution studies demonstrated that these ASDs improved the CEL dissolution rate by up to 8.2-fold compared to the crystalline form. Electrospraying presents a promising alternative to conventional methods like hot-melt extrusion (HME) and spraying drying (SD) for the production of ASDs, providing simplicity, high drug loading capability and long-term stability, thus catering to a variety of poorly water-soluble drugs. Graphical

Soluplus-stabilized 5-fluorouracil-entrapped niosomal formulations prepared via active and passive loading techniques: comparative physico-chemical evaluation

Onyinyechi Lydia Ugorji,Olisa Ivy Okoye,Chinekwu Nwangwu,Chinazom Precious Agbo,Franklin Chimaobi Kenechukwu

Encapsulation of astaxanthin in OSA-starch based amorphous solid dispersions with HPMCAS-HF/Soluplus® as effective recrystallization inhibitor

Yinglan Li,Qipeng Wei,Jianshuo Su,Huaizhen Zhang,Zhiping Fan,Zhuang Ding,Min Wen,Min Liu,Yanna Zhao

In this study, the interaction among multifunctional excipients, including polysaccharides, cellulose derivatives, and surfactants, was particularly investigated, together with its impact on the physicochemical properties of astaxanthin amorphous solid dispersions (ASTX ASDs). It was indicated that Span 20 could rapidly form hemimicelles or aggregates in the presence of hypromellose acetate succinate HF (HPMCAS-HF, HF) or Soluplus®, while octenyl succinic anhydride modified starch (OSA-starch) efficiently assisted in the coalescence inhibition of drug-excipients aggregates, which was jointly beneficial to the recrystallization inhibition of amorphous ASTX. ASTX ASDs were further prepared with OSA-starch, HPMCAS-HF/Soluplus®, and Span 20 as the wall materials. DSC, SEM, and XRD confirmed that crystalline ASTX had transformed to amorphous state in the ASDs, while FT-IR spectra provided evidence suggesting the existence of hydrogen bonds and hydrophobic interaction between ASTX and the excipients. The dissolution of ASTX ASDs in different media revealed significant promotion, while the pharmacokinetic results further demonstrated the oral bioavailability of ASTX ASDs enhanced remarkably, exhibiting 2.75-fold (SD 1 ) and 1.87-fold (SD 2 ) increase, respectively, compared to ASTX bulk powder. In summary, the cellulose derivatives-surfactant interaction had great impact on the physicochemical properties of ASTX ASDs, and their combinations exhibited great potential for delivering the hydrophobic bioactive compounds efficiently.