EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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2026
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IF 5.1
Qiang Huang,Zhiren Zou,Dian Cheng,Ruyu Gao,Lin Zhou,Wencheng Wu,Yinyin Yuan,ChangJu Chun,Yuye Huang,Guang Liang,Wenqi Wu
Co-amorphous systems have emerged as a promising strategy to enhance the aqueous solubility of poorly water-soluble drugs. Although amino acids have been widely studied as co-formers, some amino acid-based co-amorphous systems exhibit limited dissolution improvement and inadequate physical stability. In this study, glycyl- l -histidyl- l -lysine (GHK) was selected as a co-former due to its biocompatibility and multiple functional groups, which were expected to enhance the dissolution and the physical stability of pure amorphous drugs. Basic mebendazole, neutral tadalafil and acidic indomethacin were selected as the model drugs. Glycine, histidine and lysine were used as co-formers for comparison. All drug-co-former combinations were prepared by ball milling at a 1:1 molar ratio. GHK achieved complete amorphization with all three model drugs within 15 min of milling, whereas most amino acid-based mixtures remained partially crystalline even after 60 min of milling. The formation of homogeneous amorphous forms was confirmed by differential scanning calorimetry, indicated by a single glass transition temperature in the drug-GHK system. The drug-GHK systems exhibited significantly enhanced dissolution performance, including faster dissolution rates, higher drug concentration and sustained supersaturation (up to 1440 min) compared to both the pure crystalline and amorphous drugs. Furthermore, physical stability studies confirmed that GHK-based systems maintained amorphous forms for at least 6 months, outperforming both amino acid-based counterparts and pure amorphous drugs. Notably, salt formation and hydrogen bonding were associated with the observed improvements in dissolution performance and physical stability. In conclusion, GHK represents a promising co-former, expanding the design space for co-amorphous systems.
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ADVANCED FUNCTIONAL MATERIALS
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2026
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IF 19.9
Xiaoxue He,Tian Liu,Mingjia Sun,Linsheng Wu,Yinghou Wang,Jingdong Xiao,Jin Sun,Qikun Jiang
Small interfering RNAs (siRNAs) have emerged as promising therapeutics for ulcerative colitis (UC) owing to their potent anti-inflammatory effects and favorable biocompatibility. However, effective oral siRNA delivery remains challenging due to limited inflammatory cell targeting, inefficient endosomal escape, and rapid degradation in the gastrointestinal tract. To overcome these barriers, we developed a nano-in-micro modular microbead system for colon-targeted delivery of siRNA against tumor necrosis factor-α (TNF-α). This platform integrates two key components: (i) a library of ginsenoside-based lipid nanoparticles (LNPs) generated by screening natural sterol analogues, among which ginsenoside Rg3-based LNPs (Rg3@siTNF-α) were identified as optimal carriers, enabling enhanced macrophage targeting via glucose transporter-1–mediated recognition and promoting endosomal escape by attenuating Niemann–Pick C1 (NPC1)–dependent recycling; and (ii) a calcium alginate (CA) shell that encapsulated Rg3@siTNF-α to form microbeads (CA@Rg3@siTNF-α), protecting the LNPs from premature degradation in the upper gastrointestinal tract. Upon colon-specific dissolution, CA@Rg3@siTNF-α released Rg3@siTNF-α, facilitating efficient macrophage uptake, rapid endosomal escape, and lipase-responsive siRNA release. Consequently, the microbeads alleviated UC by suppressing inflammation and oxidative stress, restoring epithelial barrier integrity, and rebalancing the gut microbiota. Collectively, this work presents a spatiotemporally controlled strategy for oral siRNA delivery with multi-mechanistic therapeutic actions.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2026
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IF 5.2
Yuzhe Wang,Lu sheng,Lin Bu,Huijuan Li,Jianxin Wu,Qing Huang
Phospholipid vesicle-based permeation assay (PVPA) is widely applied as in vitro skin alternative model by mimicking stratum corneum to evaluate the transdermal application of drugs and chemicals. However, it is composed of lipid components only, which suffer from limitations of achieving accurate permeability prediction. To remedy this shortcoming, inactive immortalized human keratinocytes (HaCaT) were integrated as component to construct epidermal-mimicking model: EpiPVPA. The EpiPVPA could tolerate the pH 3–10 as well as up to 30% ethanol and was stable for 2 weeks at 4 ℃. And the permeation evaluation by Franz diffusion test of 14 drugs demonstrated that EpiPVPA model is comparable to porcine skin with strong correlation. After quantitative structure–property relationship (QSPR) analysis of physicochemical descriptors of 14 drugs, HLB, TPSA, and log P were selected as main factors applied to build multiple linear regression (MLR) equation, and the corresponding linear correlation R 2 was elevated to 0.9010. EpiPVPA model is feasible to be applied to permeation evaluation of drugs and cosmetics.
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CHEMICAL ENGINEERING SCIENCE
·
2026
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IF 5.1
Di Xu,Yunxia Li,Xiaoxiao Liang,Weiqi Liu,Yuehua Deng,Shing Fung Chow,Yanbin Jiang
Co-amorphous (CA) systems have emerged as an effective strategy for improving the dissolution of poorly water-soluble drugs. However, the screening of co-former for CA systems still relies largely on semi-empirical criteria, providing limited mechanistic insight into co-former selection and CA formation. Herein, an interpretable framework was developed for the rational design of sorafenib-based CA systems by integrating machine learning with quantum chemical analysis. Using a curated dataset and hybrid molecular descriptors, eight classification models were constructed, among which LightGBM achieved the best predictive performance. Four sorafenib CA systems were subsequently prepared and experimentally validated. Solid-state characterization supported the formation of single-phase amorphous CA systems, while FTIR and MEPS analyses suggested the involvement of intermolecular hydrogen bonding and potential electrostatic complementarity between SOR and the selected co-formers. Compared with crystalline sorafenib, the CA systems accelerated initial dissolution in both pH 1.2 HCl medium (0.5% SDS, w/v) and pH 6.8 PBS (0.5% SDS, w/v), and showed medium-dependent apparent solubility enhancement, with sorafenib-indomethacin CA reaching 57.60 ± 0.34 μg/mL after 24 h and 102.69 ± 6.48 μg/mL after 72 h in pH 6.8 PBS, corresponding to 4.1-fold and 7.7-fold increase, respectively. Sorafenib-indomethacin and sorafenib-L-phenylalanine CA systems showed relatively good resistance to recrystallization under the tested storage conditions. SHAP analysis identified descriptor-level contributions to CA formation predictions. This work provides a model-assisted and interpretable strategy for co-former prioritization and rational design of SOR-based CA systems.
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MICROCHEMICAL JOURNAL
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2026
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IF 5.2
Yuying Han,Xingyu Hou,Rui Hu,Xiaopeng Yang,Lin Hou,Xue Sun,Yuguang Lv,Lixin Ding,Ze Li
A straightforward yet sensitive dual-signal strategy was developed for the detection of melatonin (MT), based on the fluorescence properties and peroxidase-like activity of zinc‑nitrogen co-doped carbon dots (Zn,N-CDs). Through hydrogen bonding, electron transfer, as well as coordination interactions with MT, Zn,N-CDs undergo fluorescence quenching driven by the synergistic effects of static and dynamic mechanisms. Meanwhile, the generated singlet oxygen oxidizes 3,3′,5,5′-tetramethylbenzidine (TMB) into the blue-colored oxidized product (oxTMB), thus producing a ‘triggered’ dual-signal response. This platform enables simultaneous fluorescence and colorimetric analyses, offering wide linear ranges (fluorescence: 2–600 μM; colorimetry: 5–500 μM) and remarkably low detection limits (0.020 μM and 0.999 μM, respectively). Furthermore, the method exhibits excellent selectivity and has been successfully applied to pharmaceutical sample analysis, highlighting its promise for visual quality monitoring of relevant products.
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TOXICOLOGY AND APPLIED PHARMACOLOGY
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2026
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IF 3.6
Yangyi Huang,Jinfei Li,Yue Lu,Jie Cao,Xinzhi Wang,Hao Wu,Min Shen,Hongli Yu
A lectin from Pinellia ternata tubers (PTL, 12 kDa) with potent pro-inflammatory activity binds to the plasma membrane and translocates into the cytoplasm. However, its cellular entry route and inflammatory toxicity mechanisms remain unclear. Here, confocal microscopy showed that fluorescein isothiocyanate (FITC)-labeled PTL (50 μg/mL) accumulated on the cell surface and was endocytosed by RAW264.7 cells time-dependently. Pharmacological inhibition revealed that PTL uptake was mediated by the mannose receptor C-type 2 (MRC2) and predominantly via clathrin-mediated endocytosis. After endocytosis, PTL translocated to mitochondria with marked co-localization, inducing mitochondrial damage characterized by membrane potential dissipation, calcium overload, and excessive mitochondrial reactive oxygen species (mtROS) generation. These alterations promoted intracellular ROS accumulation and amplified inflammatory responses. Co-immunoprecipitation with mass spectrometry identified ATP synthase subunit beta (ATP5B) as a mitochondrial interacting protein of PTL. Their interaction was validated by molecular docking, co-localization, and microscale thermophoresis (MST). ATP5B knockdown markedly attenuated PTL (50 μg/mL)-induced ROS production, inflammatory cytokine expression, and mitochondrial injury, indicating ATP5B is a critical mediator of PTL's inflammatory toxicity. Collectively, these findings demonstrate that PTL induces mitochondrial damage and pro-inflammatory responses in RAW264.7 cells through MRC2-mediated, clathrin-dependent endocytosis and subsequent ATP5B interaction. This study establishes a mechanistic link between lectin endocytosis, mitochondrial targeting, and inflammatory toxicity, providing new insight into plant lectin-mediated immunotoxicity.
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CHEMISTRY-A EUROPEAN JOURNAL
·
2025
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IF 3.7
Mi Wang,Tianqi Liu,Hao Wang,Zhenyuan Wang,Jiaheng Zhang
Graphical This study presents a sustainable supramolecular system composed of naturally derived ingredients: PE, AHP8, and a bioactive ionic liquid from betaine and MA, which offers multiple anti-aging benefits while promoting skin permeability. The growing demand for safe and sustainable cosmetics has led to a marked inclination toward natural extracts and peptides as raw materials. In this study, we developed a sustainable system with multiple antiaging effects by combining peony extract (PE) and acetyl hexapeptide-8 (AHP8) to simultaneously treat static and dynamic wrinkles, as well as skin dullness. As the poor skin permeability of AHP8 limited its efficacy, we used a bioactive ionic liquid derived from betaine and malic acid (MA) ([Bet][MA]) as a permeation enhancer. In vitro and in vivo zebrafish experiments indicated that [Bet][MA] not only significantly enhances transdermal and cellular penetration, but also exerts synergistic anti-aging effects. While being biosafe, [Bet][MA] significantly increased the transdermal permeation, skin retention, and cellular uptake of AHP8. Theoretical calculations revealed that [Bet][MA] improved the anti-wrinkle and whitening efficacies of AHP8 and PE through supramolecular interactions; it modulated their electron cloud distribution and molecular polarity and thus intensified their affinity to target proteins. The supramolecular PE/AHP8/[Bet][MA] system demonstrated excellent radical- and reactive oxygen species-scavenging capability, collagen production, and tissue repair capability while concurrently inhibiting tyrosinase activity, motion signaling, and inflammation. The study findings pave the way for sustainable and multifunctional skincare solutions.
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WATER RESEARCH
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2022
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IF 13.4
Chaozhi Kuang,Guoshen Zeng,Yangjian Zhou,Yaoyao Wu,Dexuan Li,Yingfei Wang,Chuanhao Li
Conventional electrocatalytic degradation of pollutants involves either cathodic reduction or anodic oxidation process, which caused the low energy utilization efficiency. In this study, we successfully couple the anodic activation of sulfates with the cathodic H 2 O 2 production/activation to boost the generation of sulfate radical (SO 4 ·− ) and hydroxyl radical (·OH) for the efficient degradation of emerging contaminants. The electrocatalysis reactor is composed of a modified-graphite-felt (GF) cathode, in-situ prepared by the carbonization of polyaniline (PANI) electrodeposited on a GF substrate, and a boron-doped diamond (BDD) anode. In the presence of sulfates, the electrocatalysis system shows superior activities towards the degradation of pharmaceutical and personal care products (PPCPs), with the optimal performance of completely degrading the representative pollutant carbamazepine (CBZ, 0.2 mg L −1 ) within 150 s. Radicals quenching experiments indicated that ·OH and SO 4 ·− act as the main reactive oxygen species for CBZ decomposition. Results from the electron paramagnetic resonance (EPR) and chronoamperometry studies verified that the sulfate ions were oxidized to SO 4 ·− radicals at the anode, while the dissolve oxygen molecules were reduced to H 2 O 2 molecules which were further activated to produce ·OH radicals at the cathode. It was also found that during the catalytic reactions SO 4 ·− radicals could spontaneously convert into peroxydisulfate (PDS) which were subsequently reduced back to SO 4 ·− at the cathodes. The quasi-steady-state concentrations of ·OH and SO 4 ·− were estimated to be 0.51×10 −12 M and 0.56×10 −12 M, respectively. This study provides insight into the synergistic generation of ·OH/SO 4 ·− from the integrated electrochemical anode oxidation of sulfate and cathode reduction of dissolved oxygen, which indicates a potential practical approach to efficiently degrade the emerging organic water contaminants.
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Frontiers in Bioengineering and Biotechnology
·
2023
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IF 5.7
Xiaoxue Ren,Xiaoting Gao,Yicheng Cheng,Lingxia Xie,Liping Tong,Wei Li,Paul K. Chu,Huaiyu Wang
Mesenchymal stem cells (MSCs), with high self-renewal ability and multipotency, are commonly used as the seed cells for tissue engineering. However, the reduction and loss of multipotential ability after necessary expansion in vitro set up a heavy obstacle to the clinical application of MSCs. Here in this study, we exploit the autologous crystallization ability of biocompatible poly (ε-caprolactone) (PCL) to obtain uniformly distributed nanoneedle arrays. By controlling the molecular weight of PCL, nanoneedle with a width of 2 μm and height of 50 nm, 80 nm, and 100 nm can be successfully fabricated. After surface chemical modification with polydopamine (PDA), the water contact angle of the fabricated PCL nanoneedle arrays are reduced from 84° to almost 60° with no significant change of the nanostructure. All the fabricated substrates are cultured with bone marrow MSCs (BMMSCs), and the adhesion, spreading, proliferation ability and multipotency of cells on different substrates are investigated. Compared with the BMMSCs cultured on pure PCL nanoneedle arrays, the decoration of PDA can improve the adhesion and spreading of cells and further change them from aggregated distribution to laminar distribution. Nevertheless, the laminar distribution of cultured cells leads to a weak cell-cell interaction, and hence the multipotency of BMMSCs cultured on the PCL-PDA substrates is decimated. On the contrary, the pure PCL nanoneedle arrays can be used to maintain the multipotency of BMMSCs via clustered growth, and the PCL1 nanoneedle array with a height of 50 nm is more promising than the other 2 with regard to the highest proliferation rate and best multipotential differentiation ability of cultured cells. Interestingly, there is a positive correlation between the strength of cell-cell interaction and the multipotency of stem cells in vitro . In conclusion, we have successfully maintained the multipotency of BMMSCs by using the PCL nanoneedle arrays, especially the PCL1 nanoneedle array with a height of 50 nm, as the substrates for in vitro extension, and further revealed the importance of cell-cell interaction on the multipotency of MSCs. The study provides a theoretical basis for the behavioral regulation of MSCs, and is instructive to the design of tissue engineering scaffolds.
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PeerJ
·
2022
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IF 3.061
Jinhuang Shen,Xinhua Ma,Yubin He,Yanjun Wang,Tianhua Zhong,Yonghong Zhang
Background Ulcerative colitis is a unique inflammatory bowel disease with ulcerative lesions of the colonic mucosa. Melianodiol (MN), a triterpenoid, isolated from the fruits of the Chinese medicinal plant Melia azedarach , possesses significant anti-inflammatory properties. Objective The present study investigated the protective effects of MN on lipopolysaccharide (LPS)-induced macrophages and DSS-mediated ulcerative colitis in mice. Methods In the study, mice were given MN (50, 100, and 200 mg/kg) and 5-ASA (500 mg/kg) daily for 9 days after induction by DSS for 1 week. The progress of the disease was monitored daily by observation of changes in clinical signs and body weight. Results The results showed that MN effectively improved the overproduction of inflammatory factors (IL-6, NO, and TNF- α ) and suppressed the activation of the NF- κ B signalling cascade in LPS-mediated RAW264.7 cells. For DSS-mediated colitis in mice, MN can reduce weight loss and the disease activity index (DAI) score in UC mice, suppress colon shortening, and alleviate pathological colon injury. Moreover, MN treatment notably up regulated the levels of IL-10 and down regulated those of IL-1 β and TNF- α , and inhibited the protein expression of p-JAK2, p-STAT3, iNOS, NF- κ B P65, p-P65, p-IKK α/β , and p-I κ B α in the colon. After MN treatment, the levels of MDA and NO in colonic tissue were remarkably decreased, whereas the levels of GSH, SOD, Nrf-2, Keap-1, HO-1, I κ B α , and eNOS protein expression levels were significantly increased. Conclusion These results indicate that MN can activate the Nrf-2 signalling pathway and inhibit the JAK/STAT, iNOS/eNOS, and NF- κ B signalling cascades, enhance intestinal barrier function, and effectively reduce the LPS-mediated inflammatory response in mouse macrophages and DSS-induced intestinal injury in UC.
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JOURNAL OF MATERIALS SCIENCE
·
2022
·Vol. 58
·期 1
·383-396
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IF 4.682
Luo Lan,Lv Chengkai,Xing Yukun,Ma Fen,Kong Jie,Chen Fangfang
Abstract Molecular imprinting materials can successfully improve the efficacy and safety of drugs, thus showing good potential in the field of drug delivery. However, some difficulties in imprinted materials, such as the deep embedding of imprinting sites and poor accessibility, limit their application. Herein, we have developed porous designed molecularly imprinted polymers (MIPs) based on cleavage hyperbranched polymers for thiamine hydrochloride controlled release. By introducing hyperbranched polymers with terminal double bonds and sensitive disulfide bonds, the resulting porous MIPs (PMIPs) can expose more effective recognition sites and improve the drug-controlled release behavior, where significantly improved the drug loading (101.25 mg g −1 ) compared with the porous non-imprinted polymers (PNIPs, 16.57 mg g −1 ). Moreover, under the optimized conditions of pH 1.7 and 25 °C, the whole drug release time was increased from 16 h (PNIPs) to 32 h (PMIPs). As a result, this porous structure of MIPs designed approach provides an insight to fabricating improved imprinted constituents with higher adsorption capacity and faster recognition kinetics, which not only inspires more brilliant work in the future but also paves the way for the application of MIPs in the field of drug delivery. Graphical abstract
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CARBOHYDRATE POLYMERS
·
2022
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IF 10.723
Yuhan Yang,Yangyi Chen,Dianpeng Li,Shiyuan Lin,Hui Chen,Wei Wu,Wei Zhang
A novel delivery system based on linolenic acid (LA) conjugated chitosan (CS) polymeric micelles were proposed for improving the oral absorption of doxorubicin (DOX) through targeting intestinal fatty acid transporter. LA, as a ligand of the transporter, was grafted into CS to construct CS-LA micelles, and DOX was encapsulated into the micelles. The synthesized micelle material was identified by 1 H NMR and FT-IR. The micelles showed regular spherical shapes with a particle size of 117.1 ± 1.6 nm, drug loading of 8.77 ± 0.02 %, and critical micelle concentration (CMC) of 23.6 μg/ml. The pharmacokinetics studies showed the relative bioavailability of 166 % versus DOX·HCl. The fatty acid transport protein 4-mediated intestinal uptake process of micelles was confirmed by the intracellular uptake, immunofluorescent imaging and permeation test. These findings confirmed the potential of CS-LA micelles as an effective oral delivery vehicle, and fatty acid transporter as a target spot for enhancing intestinal drug absorption.
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