Latest ArticlesSmall-angle neutron scattering (SANS) is a non-destructive structural characterization technique based on neutron-matter interactions, capable of providing microstructural information at the nanometer to micrometer scale (1-1 000 nm), including particle size distribution, morphological features, internal phase structures, and intermolecular interactions in pharmaceutical formulations. With the rapid development of nanodrug delivery systems (e.g., liposomes, polymeric micelles, lipid nanoparticles) and biologics (e.g., monoclonal antibodies, mRNA vaccines), conventional characterization techniques (e.g., electron microscopy, dynamic light scattering) face limitations in analyzing complex drug systems. Owing to its high sensitivity to light elements, exceptional penetration depth, and isotope discrimination capability, SANS offers unique advantages for probing the microstructure of pharmaceutical formulations. This review systematically summarizes recent advances in SANS applications for drug characterization, focusing on its pivotal role in elucidating the structure of nanodrug carriers, monitoring conformational dynamics of biologics, and investigating the self-assembly behavior of active pharmaceutical ingredients (APIs). Furthermore, the challenges of SANS in sample preparation, data analysis, and facility accessibility are discussed, along with future perspectives on integrating SANS with emerging technologies such as artificial intelligence and multiscale modeling. This review aims to provide new insights and technical support for the rational design and performance optimization of advanced drug formulations.
In recent years, the research of transdermal drug delivery systems (TDDS) represented by patches and gel plasters is in the ascendant. The interactions between drugs, pressure-sensitive adhesives, permeation enhancers and skin components, including hydrogen bonds, ionic interactions, dipole-dipole interactions, etc., play a key role in regulating the release and penetration of drugs in transdermal patches, thus affecting the efficiency of transdermal absorption of drugs. Infrared spectroscopy, molecular simulations or molecular docking, differential scanning calorimetry, Raman spectroscopy, nuclear magnetic resonance and other methods have been widely used to characterize multiple intermolecular interactions in patches. The aim of this review is to summary the molecular mechanisms of drug release from patches and transdermal permeation processes, provide useful theoretical guidance for the design and research of novel transdermal drug delivery systems.
The application of microneedle technology in biomedicine has attracted widespread attention due to its versatility in tissue sampling, biosensing and drug delivery. In particular, drug-loaded microneedle formulations can directly penetrate the stratum corneum to deliver drugs, enhance drug delivery efficiency, and achieve the purpose of disease treatment, which is characterized by high efficiency, portability, low trauma, and high controllability. When combined with smart responsive materials, microneedles enable precise drug delivery, improving targeting accuracy for diseases such as tumors while minimizing toxic side effects on normal tissues and cells. In this review, we introduce the history of microneedle technology and highlight its applications in smart-responsive systems for oncology therapy. We also discuss the current challenges and obstacles faced by microneedle technology in oncology therapy and clinical translation. Finally, we provide prospective recommendations on the current situation, aiming to inspire new ideas and directions for the development of related technologies.
Hair follicle is the organ of hair growth. Hair growth is highly associated with hair follicle cycle, which can be assessed by both promoting hair follicles from telogen to anagen and prolonging the anagen duration. In this study, according to the investigation of the hair follicle cycle in C57BL/6J mice, an evaluation model for the activity of hair follicles entering the anagen was established. Then, the hair follicle cycle was synchronized by beeswax-depilation, and the correspondence between the skin phenotypes and each phase of the hair follicle cycle was quantified, and the efficacy evaluation model for prolonging the anagen duration was innovatively constructed. Two mouse models established in this study can be utilized for active substances discovery and pharmacodynamic evaluation in vivo, which provides the methodology for development of hair growth promoting-drugs and health products. All animal experiments were approved by the Animal Care & Welfare Committee of Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (approval numbers: 00001932, 00001933, 00007786, and 00007787).
Nineteen compounds were isolated from the dichloromethane portion of the ethanol extract of Chinese Yam (Dioscorea opposita Thunb.) peel, using various chromatographic techniques including: silica gel column chromatography, medium-pressure liquid chromatography, Sephadex LH-20 gel column chromatography, and preparative high-performance liquid chromatography. Based on the physicochemical properties and spectral data, their structures were determined as follows: six phenanthrenes: 7′-hydroxybleformin E (1), 1,7-dihydroxy-5-methoxy-9,10-dihydrophenanthrene (2), 6-methoxycoelonin (3), 6-hydroxy-2,4,7-trimethoxyphenanthrene (4), 2,7-dihydroxy-4,6-dimethoxyphenanthrene (5), 5,7-dimethoxy-2,3-phenanthrenediol (6); three bibenzyls: dihydropinosylvin (7), 2′,3-dihydroxy-5-methoxybibenzyl (8), demethyl batatasin Ⅳ (9); eight diarylheptanoids: 1,7-bis(4-hydroxyphenyl)-1,5-epoxy-3-hydroxyheptane (10), engelheptanoxide C (11), diosniponol A (12), (+)-hannokinol (13), (3S,5S)-3,5-dihydroxy-1-(4-hydroxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane (14), (3S,5S)-3,5-dihydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptane (15), hexahydrocurcumin (16), (5S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)-3-heptanone (17); other compounds: one alkaloid, feruloyltyramine (18), and one fatty acid, octadecadienoic acid-2,3-dihydroxypropyl ester (19). Compound 1 is a new compound, whereas the 1H NMR and 13C NMR spectral signals of 2 were fully attributed. compounds 2, 11, 16-19 were isolated from the Dioscoreaceae family for the first time, while compounds 3, 6, and 12 were the first to be reported from D. opposita. Among these, thirteen compounds showed differential inhibitory activities against α-glucosidase.
Thirteen compounds (1-13) were isolated from the ethanol extract of an endophytic fungus Cercophora sp. UJN-EF001 derived from Vaccinium bracteatum, using normal-phase silica gel column chromatography (CC), reversed-phase C18 CC and high-performance liquid chromatography. The structures of these isolates were elucidated through spectroscopic methods including high-resolution mass spectrometry, nuclear magnetic resonance and electronic circular dichroism. Among them, two (1 and 2) were previously unreported molecules, two (3 and 4) were obtained for the first time as natural products, and nine (5-13) were isolated for the first time from the genus Cercophora. All 13 compounds were evaluated for their inhibitory activities against α-glucosidase and nitric oxide (NO) production. As a result, none of them exhibited significant inhibition toward α-glucosidase, while compound 13 displayed moderate inhibition against lipopolysaccharide-induced release of NO in RAW264.7 macrophages with an IC50 value of 34.3 ± 3.8 μmol·L-1.
Shexiang Tongxin Dropping Pill (STDP), a compound oral preparation of traditional Chinese medicine, has the therapeutic effects of improving myocardial ischemia and relieving chest tightness and pain. It is often used in combination with chemical drugs for cardiovascular diseases in clinical practice. In this paper, the inhibitory effects of STDP on 17 human transporters were studied by cellular accumulation experiments using overexpressing transgenic cell models, including important transporters in the intestine (PEPT1, OATP2B1, MDR1, BCRP), liver (OATP1B1, OATP1B3, OCT1, OAT2), kidney (OAT1, OAT3, OAT4, OCT2, MATE1, MATE2-K), and heart (OCTN1, OCTN2, OCT3). The results showed that STDP inhibited the renal cation transport system (OCT2, MATE1/2-K), but had no significant inhibitory effect on the other 14 transporters. Since the commonly co-administered drugs are not substrates of OCT2 and MATE1/2-K, atenolol and procainamide, the potential co-administered drugs of STDP, were selected as substrates for further study. The results reveled that STDP inhibited the transport of atenolol mediated by MATE1 and MATE2-K, as well as the transport of procainamide mediated by MATE1. Further study showed that the extracts of plasma, liver, and kidney from mice orally administered with STDP, even at 10-folds of clinical dose, merely inhibited MATE1-mediad transport of atenolol by 20%, without inhibiting MATE2-K-meidated transport of atenolol and MATE1/2-K-mediated transport of procainamide. It is speculated that at the clinical dose, STDP is unlikely to significantly affect the renal excretion of the two drugs. The above results suggest that at the clinical dose, STDP is unlikely to induce significant drug-drug interactions (DDIs) due to the inhibition of the above transporters. The animal experiments have been approved by the Animal Ethics Committee of Zhejiang University (approval number: ZJU20230086).
To explore the effects of Zhimu extract on the absorption and pharmacokinetic process of puerarin, thus to elucidate the scientific connotation of the compatibility application of Gegen-Zhimu herb pair from the perspective of P-glycoprotein (P-gp) regulation, a rapid and sensitive quantification method for puerarin in biological samples was established based on HPLC-UV technology. Combined with the rat single-pass intestinal perfusion model and pharmacokinetic experiments, with the classic P-gp inhibitor verapamil as control, the effects of Zhimu extract on the absorption and metabolism process of puerarin were investigated. The established HPLC method for puerarin in intestine perfusate and plasma samples met the requirements for quantitative analysis of biological samples. The Ka and Papp values of puerarin in the duodenal segment were significantly higher than those in the jejunal and ileal segments (P < 0.000 1). Co-administration with Zhimu extract or verapamil significantly increased the Ka and Papp values of puerarin in the duodenal segment (P < 0.000 1). Co-administration with high-dose Zhimu extract or verapamil significantly increased the Cmax of puerarin in rats to (1.017 ± 0.25) µg·mL-1 and (1.827 ± 0.87) µg·mL-1 (P < 0.05), respectively, and AUC0-∞ also significantly increased (P < 0.05), reaching 1.37-fold and 2.25-fold that of the puerarin group, respectively. Puerarin is best absorbed in the duodenal segment; by inhibiting the efflux of P-gp, Zhimu extract can promote the absorption of puerarin in the duodenal segment, increase its plasma concentration, and effectively improve the oral bioavailability of puerarin, which suggests the mechanism underlying the compatibility of Gegen-Zhimu herb pair. This experiment was approved by the Animal Ethics Committee of Naval Medical University (approval No.: NMUARE-21077).
The masking level of adverse taste of drugs, defined as taste-masking efficiency, directly affects the palatability of drugs, which in turn affects medication compliance. However, there is no effective and unified evaluation method. In this paper, three preparations with different dosage form and varied solubility, fexofenadine hydrochloride dry suspension, calcium carbonate D3 particles and compound polyethylene glycol electrolyte powder, were selected to carry out simultaneous research on TS-5000Z, Astree Ⅱ V5 and iTongue20 electronic tongues. Through the determination of judgment criteria for reasonable solution preparation, effective sensor cleaning and repeatable sample testing, combined with high-dimensional data similarity discrimination methods such as principal component analysis and Euclidean distance, an evaluation method of taste-masking efficiency for drugs was established based on the design of reference solutions and determination of taste similarity between sample solution and reference solution. The above method was reproducible with comparable results among instruments, and with consistent results with human sensory evaluation. The above method is a standardized new method that can be used for multi-type drugs and multi-principle equipment, which provides technical support for the comparison of taste palatability between pharmaceutical preparations.
Proteolysis-targeting chimeras (PROTACs) leverage their "event-driven" mechanism to target traditionally undruggable proteins inaccessible to conventional small molecule inhibitors, thereby significantly expanding the therapeutic landscape of drug discovery. Furthermore, PROTACs overcome the resistance associated with small molecule inhibitors by achieving complete degradation of target proteins rather than transient functional inhibition. However, their sustained catalytic activity may induce off-target effects and systemic toxicity. To mitigate these limitations, stimuli-responsive PROTAC prodrug systems have emerged as a promising strategy to spatiotemporally control PROTAC activation within tumor microenvironments. PROTAC prodrug systems demonstrate tumor microenvironment-responsive activation through endogenous/exogenous stimuli (e.g., light, enzymes, reactive oxygen species), enabling spatiotemporal control of PROTAC liberation. This precision engineering strategy significantly reduces off-target toxicity while maintaining potent on-target protein degradation efficacy. This review provides a systematic overview of cutting-edge advances in stimuli-activatable PROTAC platforms, critically examines current limitations and challenges in the field, and proposes strategic directions for future development to accelerate the evolution of precision cancer therapeutics.
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