查找使用阿拉丁产品的科研文献

Beeswax sacrificial support and latex curing for high-fidelity semi-solid extrusion 3D printed sustained-release tablets

Haozheng Zhang,Chuansheng Yang,Wenhao Yuan,Qihang Dong,Yuhong Xu,Chu Chu,Tabussam Tufail,Farhan Saeed,Yan Yang

Semi-solid extrusion (SSE) 3D printing offers significant potential for fabricating personalized oral dosage forms, thanks to its mild processing conditions. However, post-printing drying often induces structural collapse and deformation due to solvent evaporation, severely compromising geometric fidelity. While freeze-drying can mitigate deformation, it is time-intensive and yields highly porous structures with inferior mechanical strength. This study introduces a dual strategy employing a phase-change sacrificial support and thermal curing to overcome these limitations. A printable matrix was formulated using microcrystalline cellulose and hydroxypropyl methylcellulose (HPMC) as rheological modifiers, with Eudragit® RL 30D aqueous dispersion serving as the sustained-release polymer and beeswax as a sacrificial phase. The optimized tablets demonstrated superior mechanical integrity, with Young's modulus increasing by 67%. During thermal curing at 80°C, the dispersed Eudragit® RL pseudo-latex underwent coalescence and formed an insoluble matrix, creating an insoluble polymeric network that reinforced the structure and modulated drug release. Crucially, beeswax (melting range 62–67°C) provided mechanical support during the critical drying phase at 50°C, preventing structural collapse, before being sacrificially removed during the 80°C curing step. This approach successfully produced high-fidelity, diclofenac sodium-loaded tablets with tunable release profiles governed by the Eudragit® RL-to-HPMC ratio. These findings present a robust strategy for producing dimensionally stable, mechanically strong, and personalized sustained-release formulations via SSE 3D printing.

Bone-Targeting Microspheres Enable Sustained Release of CD301b+ Macrophage-Derived Small Extracellular Vesicles to Promote Bone Repair

Xiang Gao,Shanshan Ma,Yeying Dong,Fengkai Yang,Rui Huang,Xiudan Zheng,Zhijun Liu,Hong Zheng,Fatai Lu,Thomas Groth,Mingyan Zhao

Rationale Large bone defects often exceed the body’s intrinsic capacity for self-repair. Successful bone healing depends on a coordinated immune transition alongside tightly coupled angiogenesis and osteogenesis, in which macrophages play a key regulatory role. Therefore, ideal bone-regenerative materials should integrate immunomodulatory, pro-angiogenic, and osteogenic functions. Methods and Results Small extracellular vesicles (sEVs) from CD301b + macrophages (CD301b⁺-sEVs) are isolated by ultracentrifugation for inclusion in a bone-targeting microsphere system fabricated by microfluidic technology through dynamic Schiff-base cross-linking of alendronate-functionalized succinylated chitosan with oxidized sodium alginate allowing pH-responsive release of CD301b⁺-sEVs. Transcriptome sequencing and comprehensive in vitro studies reveal that CD301b⁺-sEVs possess the ability to modulate immune homeostasis by promoting macrophage polarization toward the pro-repair M2 phenotype, upregulate angiogenic factors that can enhance vascularization as seen by HUVEC sprouting assay, and contain RNA that stimulate osteogenic differentiation of BMSCs through activation of the Akt/GSK-3β/β-catenin signaling pathway. Preclinical studies with a rat calvaria model show that microspheres loaded with CD301b + -sEVs significantly promote bone regeneration in comparison to microsphere controls. Conclusion This study not only overcomes key limitations of conventional sEVs therapies such as poor retention and instability, but also provides an innovative “targeted localization, intelligent release, and multifunctional synergy” strategy, offering a minimally invasive and highly effective therapeutic platform for bone repair.

Intercalation of procainamide into magadiite by multi-step ultrasonic ion exchanges and the sustained release of PA

Guo Fang,Liu Yijun,Zhong Yu,Feng Wanyun,Shang Xiaoqiang,Chen Yufeng

In order to improve the loading capacity of the drug delivery system based on magadiite for procainamide (PA), the cationic PA was inserted into the interlayer of magadiite by the intercalation of tetra-n-butylammonium ions and multi-step ultrasonic ion exchange. X-ray diffraction, compositional analyses, and IR results confirmed that the cationic PA was successfully loaded into the interlayer of magadiite, and the loading capacity of the drug delivery system based on magadiite for PA was about 25.0%. Thermogravimetric analysis indicated that the thermal stability of PA was obviously improved after it was loaded into the interlayer of magadiite. Drug release revealed the sustained and controlled release of PA from drug delivery system either in phosphate buffer solution (PBS, pH = 7.4, simulating intestinal fluid) or in HCl solution (pH = 1.35, simulating gastric fluid). This sustained release of drugs will be beneficial to improve the availability and efficacy of drugs. Moreover, the kinetic behavior of drug release either in PBS or in HCl can be fitted to ExpAssoc model. Nuclear magnetic resonance (NMR) results indicated that there is an interaction between the magadiite and PA in the drug delivery system, and this interaction may determine the kinetic behavior of drug release. The present work may provide a refer for improving the loading capacity of positively charged drugs in some layered silicates, which would be important in medical field.

Pea isolate protein/β-cyclodextrin/CQDs microcapsules improve stability and in vitro sustained release of fish oil

Wenyuchu Chen,Fang Tian,Yongjing Xu,Yujin Li,Weiliang Guan,Chenyang Lu,Sheng Hu,Luyun Cai

Fish oils (FOs) are rich in omega-3 polyunsaturated fatty acids, which provide several health benefits. However, their oral bioavailability and stability are often limited due to the oxidation of polyunsaturated fatty acids, which degrade the oil's nutritional and sensory properties over time. In this study, FO microcapsules were prepared using pea protein isolate (PPI), β-cyclodextrin (β-CD), and carbon quantum dots (CQDs) as wall materials through a freeze-drying method. The results demonstrated that the use of PPI/β-CD/CQDs composite significantly improved the encapsulation efficiency, stability, and antioxidant properties of the microcapsules, suggesting a promising approach for enhancing the shelf-life and health benefits of fish oil. Additionally, the peroxide value (POV) and thiobarbituric acid (TBA) values of the microcapsules increased with temperature and storage time. Notably, the incorporation of CQDs markedly improved the antioxidant properties of the microcapsules, thereby extending their storage stability. In vitro gastrointestinal digestion simulations demonstrated that microencapsulation facilitated the absorption of beneficial substances in fish oil within the human gut. This study offers valuable insights into the development of more efficient fish oil microcapsules for potential applications in food and pharmaceutical applications.

Transdermal Drug Delivery System of Linagliptin Sustained-release Microparticle Gels: In vitro Characterization and In vivo Evaluation

Liu JiaYan,Guo Song,Hong Shuai,Piao Jingshu,Piao Mingguan

Background: Linagliptin (LNG) exhibits poor bioavailability and numerous side effects, significantly limiting its use. Transdermal drug delivery systems (TDDS) offer a potential solution to overcome the first-pass effect and gastrointestinal reactions associated with oral formulations. Objective: The aim of this study was to develop LNG microparticle gels to enhance drug bioavailability and mitigate side effects. Methods: Linagliptin hyaluronic acid (LNG-HA) microparticles were prepared by spray drying method and their formulation was optimized via a one-factor method. The solubility and release were investigated using the slurry method. LNG-HA microparticle gels were prepared and optimised using in vitro transdermal permeation assay. The hypoglycaemic effect of the LNG-HA microparticle gel was examined on diabetic mice. Results: The results indicated that the LNG-HA microparticle encapsulation rate was 84.46%. Carbomer was selected as the gel matrix for the microparticle gels. Compared to the oral API, the microparticle gel formulation demonstrated a distinct biphasic release pattern. In the first 30 minutes, only 43.56% of the drug was released, followed by a gradual release. This indicates that the formulation achieved a slow-release effect from a dual reservoir system. Furthermore, pharmacodynamic studies revealed a sustained hypoglycemic effect lasting for 48 hours with the LNG microparticle gel formulation. Conclusion: These findings signify that the LNG microparticle gel holds significant clinical value for providing sustained release and justifies its practical application.

Long effective tea tree oil/mesoporous silica sustained release system decorated by polyethyleneimine with high antibacterial performance

Huayao Chen,Zhichuan Shen,Peiting Wu,Hongjun Zhou,Li Hao,Hua Xu,Xinhua Zhou

Preparation of Tea Tree Oil/Poly(styrene-butyl methacrylate) Microspheres with Sustained Release and Anti-Bacterial Properties

Guanquan Lin,Huayao Chen,Hongjun Zhou,Xinhua Zhou,Hua Xu

Using butyl methacrylate (BMA) and styrene (St) as monomers and divinylbenzene (DVB) as a crosslinking agent, P(St-BMA) microspheres were prepared by suspension polymerization. Tea tree oil (TTO) microspheres were prepared by adsorbing TTO on P(St-BMA) microspheres. The structure and surface morphology of P(St-BMA) microspheres and TTO microspheres were characterized by Fourier transformed infrared spectroscopy (FTIR), optical microscopy, and Thermogravimetric analysis (TGA). In doing so, the structural effect of P(St-BMA) microspheres on oil absorption and sustained release properties could be investigated. The results show that the surface of the P(St-BMA) microspheres in the process of TTO microsphere formation changed from initially concave to convex. The TTO microspheres significantly improved the stability of TTO, which was found to completely decompose as the temperature of the TTO increased from about 110 °C to 150 °C. The oil absorption behavior, which was up to 3.85 g/g, could be controlled by adjusting the monomer ratio and the amount of crosslinking agent. Based on Fickian diffusion, the sustained release behavior of TTO microspheres was consistent with the Korsmeyer-Pappas kinetic model. After 13 h of natural release, the anti-bacterial effect of the TTO microspheres was found to be significantly improved compared to TTO.

Solid-Phase Synthesis of Cellulose Acetate Butyrate as Microsphere Wall Materials for Sustained Release of Emamectin Benzoate

Aimin Huang,Xuanhai Li,Xingtang Liang,Yanjuan Zhang,Huayu Hu,Yanzhen Yin,Zuqiang Huang

Emamectin benzoate (EB), a widely used pesticide, is prone to decomposition by ultraviolet light and suffers from the corresponding loss of efficacy. The timed release of EB based on microspheres is one of the effective methods to solve this issue. As a non-toxic cellulose ester, cellulose acetate butyrate (CAB) is regarded as one of the best wall-forming materials for microcapsules with a good controlled release performance. Herein, two methods—mechanical activation (MA) technology and a conventional liquid phase (LP) method—were employed to synthesize different CABs, namely CAB-MA and CAB-LP, respectively. The molecular structure, rheological property, and thermal stability of these CABs were investigated. The two CABs were used to prepare microspheres for the loading and release of EB via an o/w (oil-in-water) solvent evaporation method. Moreover, the performances such as drug loading, drug entrapment, and anti-photolysis of the drug for these microspheres were studied. The results showed that both CABs were available as wall materials for loading and releasing EB. Compared with CAB-LP, CAB-MA presented a lower molecular weight and a narrower molecular weight distribution. Moreover, the MA method endowed the CAB with more ester substituent groups and less crystalline structure in comparison to the LP method, which had benefits including pelletizing and drug loading.Keywords:cellulose acetate butyrate;solid-phase synthesis;mechanical activation;microspheres;emamectin benzoate;release

Synthesis of surfactant-modified ZIF-8 with controllable microstructures and their drug loading and sustained release behaviour

Xinyu Xu,Ye Liu,Zhaoming Guo,Xue-Zhi Song,Xiuyu Qi,Zideng Dai,Zhenquan Tan

Metal-organic frameworks (MOFs) as drug carriers have many advantages than traditional drug carriers and have received extensive attention from researchers. However, how to regulate the microstructure of MOFs to improve the efficiency of drug delivery and sustained release behaviour is still a big problem for the clinical application. Herein, the authors synthesise surfactant-modified ZIF-8 nanoparticles with different microstructures by using different types of surfactants to modify ZIF-8. The surfactant-modified ZIF-8 nanoparticles have the larger specific surface area and total micropore volumes than the original ZIF-8, which enables doxorubicin (DOX) to be more effectively loaded on the drug carriers and achieve controlled drug sustained release. Excellent degradation performance of ZIF-8 nanoparticles facilitates the metabolism of drug carriers. The formulation was evaluated for cytotoxicity, cellular uptake and intracellular location in the A549 human non-small-cell lung cancer cell line. ZIF-8/DOX nano drugs exhibit higher cytotoxicity towards cells in comparison with free DOX, suggesting the potential application in nano drugs to cancer chemotherapy.

A predictive release kinetic model guiding the rational design of sustained release solid dispersions with insoluble carriers

Kai Ge,Yuanhui Ji

Flurbiprofen (FBU) is a nonsteroidal anti-inflammatory drug with short half-life, requiring frequent dosing and leading to potential gastrointestinal side effects. To address these limitations, this study aimed to develop the FBU sustained release solid dispersion using insoluble carriers (Eudragit RL100/RS100). The release kinetics of various formulations were investigated, and the release mechanisms were analyzed using an internal and external diffusion kinetic model. The powder X-ray diffraction and differential scanning calorimetry results confirmed the amorphous nature of FBU in all solid dispersions. It was found that the formulation composition significantly influenced the release kinetics, where low permeable Eudragit RS slowed the release and the incorporation of the soluble polymer PVP enhanced it. An optimized formulation with 10% PVP achieved nearly complete release with desirable sustained release characteristics. The kinetic model successfully modeled the release profiles with a maximum average relative deviation (ARD) of 11.8%, revealing that the release was predominantly controlled by internal diffusion. The model was further utilized to predict the release behavior for varying carrier compositions and particle sizes successfully, demonstrating its ability in guiding the rational design of formulations based on insoluble polymeric carriers. This work underscores the critical role of mechanistic modeling in transitioning from empirical formulation screening to rational design.

Preparation and sustained release bacteriostatic performance of pH-responsive complex hydrogel bacteriostatic microspheres for oral drug delivery

Wenqin Xu,Xing Li,Xianmei Wu,Guanghua Pan,Nanchun Chen,Xiuli Wang,Qinglin Xie

pH-responsive hydrogel antibacterial microspheres were prepared by complex coacervation method and used as drug carriers to load the antibiotic substitute potassium diformate (KDF). The results showed that the three-dimensional network structure of the composite hydrogel was formed among the polysaccharide components, and Zeolite A loaded with KDF was uniformly dispersed in it. The results of drug release behavior and kinetics in vitro showed that the drug release rate was higher and the release mechanism followed the Ritger-Peppas model, which indicated that the antibacterial microspheres had a good pH response. In vitro, the carrier showed broad-spectrum antibacterial activity, good biocompatibility, and degradability.

Sustained Release of Dicumarol via Novel Grafted Polymer in Electrospun Nanofiber Membrane for Treatment of Peritendinous Adhesion

Yanhao Li,Chengfang Hu,Bo Hu,Jian Tian,Gang Zhao,Chuandong Cai,Yuange Li,Zhenyu Sun,Shuo Wang,Sa Pang,Rong Bao,Zaijing Tao,Huajiang Chen,Jinglei Wu,Shen Liu

The prevention and treatment of post-traumatic peritendinous adhesion (PA) have always been a great difficulty for orthopedic surgeons. Current treatments include resecting surgery, non-steroidal anti-inflammatory drugs (NSAIDs) usage and implantable membranes, often target single disease pathogenic processes, resulting in unfavorable therapeutic outcomes. Here a polylactic acid (PLA)-dicumarol conjugates-electrospun nanofiber membrane (ENM) (PCD) is generated, which can achieve spatial accuracy and temporal sustainability in drug release. It is further demonstrated that PCD possesses a significantly higher and more sustainable drug release profile than traditional drug-loading ENM. By providing a physical barrier and continuous releasing of dicumarol, PCD implantation significantly reduces tissue adhesion by 25%, decreases fibroblasts activity and inhibits key fibrogenic cytokine transforming growth factor beta (TGF β ) production by 30%, and improves the biomechanical tendon property by 14.69%. Mechanistically, PCD potently inhibits the connexin43 (Cx43) and thereby tunes down the fibroblastic TGF β /Smad3 signaling pathway. Thus, this approach leverages the anti-adhesion effect of dicumarol and drug release properties of grafted copolymer ENM by esters to provide a promising therapeutic strategy for patients who suffer from PA.