Shu Zhang

Localized rectal delivery is a promising strategy for ulcerative colitis, as it may increase drug exposure at inflamed sites in the distal colorectum while reducing systemic exposure. However, many natural anti-inflammatory small molecules, including β-sitosterol, are hydrophobic and have poor aqueous dispersibility, limiting their formulation and therapeutic use. Conventional rectal dosage forms typically have fixed structures, making it difficult to tailor drug-release behavior. To address these challenges, a β-sitosterol-loaded self-emulsifying lipid suppository was fabricated using semisolid extrusion (SSE) three-dimensional (3D) printing, and the ability of the internal architecture to modulate early in vitro drug release was investigated. The Gelucire® 44/14-based matrix exhibited shear-thinning behavior and temperature-dependent softening, enabling SSE 3D printing. Upon contact with an aqueous medium, the printed suppositories formed submicron dispersions. Liquefaction and self-emulsification times ranged from 18.27 to 24.27 min and from 4.33 to 8.54 min, respectively. A representative formulation had a droplet size of 370.67 ± 39.09 nm and a polydispersity index of 0.27 ± 0.04. Fourier transform infrared, differential scanning calorimetry, and X-ray diffraction analyses indicated good drug–matrix compatibility and reduced β-sitosterol crystallinity, suggesting partial solubilization within the lipid matrix. With the matrix composition and external geometry held constant, in vitro release was adjusted by varying the internal pore architecture and nominal infill density. Lower-infill-density structures promoted faster medium penetration and earlier β-sitosterol release, whereas higher-infill-density structures slowed release by increasing structural resistance and diffusion-path tortuosity. These results demonstrate the feasibility of using SSE 3D printing to produce structure-modulated rectal dosage forms containing poorly water-soluble natural compounds.

Precision therapy for ulcerative colitis (UC) relies on achieving sufficiently high drug concentrations at the site of inflammation. However, many natural anti-inflammatory small molecules, including β-sitosterol, exhibit inherent hydrophobicity and poor bioavailability, limiting their therapeutic potential. Conventional rectal dosage forms typically possess structurally fixed designs, making it difficult to precisely control the drug dose and release kinetics according to patient-specific therapeutic needs, thereby restricting clinical efficacy during local administration. To address these challenges, a β-sitosterol self-emulsifying lipid suppository was fabricated using semisolid extrusion (SSE) three-dimensional (3D) printing, and a programmable “structure-driven release” strategy was proposed for controllable drug delivery. The self-emulsifying Gelucire 44/14 matrix exhibited shear-thinning and thermoresponsive properties, enabling 3D printing under near-ambient conditions. Upon contact with physiological fluids, the suppository rapidly generated a stable oil-in-water nanoemulsion (self-emulsification time: 4.54 ± 0.17 min; droplet size: 386.16 ± 22.55 nm; polydispersity index: 0.26 ± 0.02), markedly improving the apparent solubility of the poorly water-soluble drug. Spectroscopic and thermodynamic analyses confirmed the stable molecular dispersion of the drug in the lipid matrix. Without altering the chemical composition, the release kinetics could be programmed through structural engineering. By precisely tuning the internal pore architecture and infill density of the printed suppository, the system enabled controllable transitions from rapid drug release to sustained release. This study establishes a structure-driven programmable delivery strategy that bridges 3D architectural design with pharmacokinetic regulation, exhibiting potential for the colon-targeted delivery of poorly soluble natural anti-inflammatory agents and for personalized therapy of mucosal inflammatory diseases, including UC.

Sebum plays a dual role in skin homeostasis, maintaining barrier function and providing antimicrobial defense. However, its dysregulation drives the pathophysiology of common skin diseases. This review explains that abnormal sebum secretion promotes acne vulgaris by inducing follicular occlusion and Cutibacterium acnes (C. acnes) proliferation, while altered composition impairs the epidermal barrier. Key factors such as high-glycemic diets, androgen fluctuations, and environmental conditions significantly influence sebaceous gland activity. The underlying molecular mechanisms involve inflammatory and hormonal pathways, including dysregulation of peroxisome proliferator-activated receptor gamma (PPARγ) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling. We conducted a systematic literature search using keywords related to sebum physiology and pathology. This review also discusses emerging therapeutic targets and the potential of advanced sebaceous gland models for future research. This synthesis provides a theoretical foundation for developing targeted interventions in dermatology and cosmetics.

Background: Slow healing of skin wounds is a major health problem affecting millions of people each year, and traditional dressings have limited effectiveness in treating them. Gallic acid has anti-inflammatory, antibacterial and antioxidant properties, and combined with nanotechnology can improve its solubility and provide new directions for wound treatment. Methods: In this study, Gallic acid nanocrystals (GC-NCs) were prepared by a “top-down” method, and GC-NCs were combined with a polyacrylic acid matrix to form Gallic acid nanocrystal hydrogel (GC-NCs-Gel) by co-gelation. The micromorphology, mechanical properties, adhesion properties and bioactivity of GC-NCs-Gel were tested. Finally, the ability of GC-NCs-Gel to promote wound healing and inhibit scar formation was evaluated in a rat whole skin defect model. Results: The average particle size of GC-NCs was 348.20 ± 1.42 nm, and GC-NCs-Gel had a honeycomb porous structure with excellent swelling properties (963%), water vapor transmission rate (2400 g/m²/h), tensile stress (28,000 Pa), and adhesive strength (9.6 kPa). GC-NCs-Gel also demonstrated a sustained and controlled drug release property after 48 h of release, the cumulative release was about 57%, and GC-NCs-Gel reached the highest cumulative permeability of 127.2 μg/cm² within 6 h. In vitro experiments showed that the inhibition circle diameter of GC-NCs-Gel was 39.75 ± 0.61 mm for S. aureus and 21.52 ± 0.06 mm for E. coli. The free radical scavenging efficiency of GC-NCs-Gel reached 77.7% in the DPPH assay and up to 98.6% in ABTS. In vivo experiments showed that GC-NCs-Gel accelerated wound healing by promoting neovascularization, epidermal regeneration and collagen deposition. Conclusion: In this study, a GC-NCs-Gel with anti-inflammatory, antibacterial as well as antioxidant and wound tissue adhesion was prepared. This multi-functional hydrogel has significant advantages in wound healing, and is expected to provide a new and effective means of wound treatment in the clinic.

Danggui–Jianzhong decoction (DGJZ) is a famous classical traditional Chinese medicine formula, which ingredients are complex and the quality is difficult to control. Our study aimed to identify the overall chemical profile of DGJZ qualitatively by ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and UPLC. A total of 77 components, including terpenoids, flavonoids, phenolic acids, gingerols and other components, were firstly detected and characterized by UPLC-Q-TOF-MS and 18 peaks marked after analyzing the UPLC fingerprint. Finally, paeoniflorin, liquiritin, ferulic acid, cinnamic acid, glycyrrhizic acid and 6-gingerol were quantified, which was validated in terms of linearity, precision, accuracy, repeatability and recovery. Taken together, the chemical constitutes of DGJZ were systematically identified and a reliable quantitative method coupled with fingerprint analysis was successfully employed for evaluating the holistic quality, which will provide a robust foundation for the quality control of DGJZ.

Today, about 50% of men and 15–30% of women are estimated to face hair-related problems, which create a significant psychological burden. Conventional treatments, including drug therapy and transplantation, remain the main strategies for the clinical management of these problems. However, these treatments are hindered by challenges such as drug-induced adverse effects and poor drug penetration due to the skin’s barrier. Therefore, various efforts have been undertaken to enhance drug permeation based on the mechanisms of hair regrowth. Notably, understanding the delivery and diffusion of topically administered drugs is essential in hair loss research. This review focuses on the advancement of transdermal strategies for hair regrowth, particularly those involving external stimulation and regeneration (topical administration) as well as microneedles (transdermal delivery). Furthermore, it also describes the natural products that have become alternative agents to prevent hair loss. In addition, given that skin visualization is necessary for hair regrowth as it provides information on drug localization within the skin’s structure, this review also discusses skin visualization strategies. Finally, it details the relevant patents and clinical trials in these areas. Together, this review highlights the innovative strategies for skin visualization and hair regrowth, aiming to provide novel ideas to researchers studying hair regrowth in the future.

Archidendron clypearia (A. clypearia), a Fabaceae family member, is widely used as an anti-inflammatory herbal medicine; however, its antibacterial and antidiabetic properties have not been extensively investigated. This study aimed to systematically analyze the antibacterial and antidiabetic components of A. clypearia by utilizing a combination of analytical methods. First, ten different polarity extracts were analyzed through ultra-performance liquid chromatography (UPLC), and their antibacterial and antidiabetic activities were evaluated. Then the spectrum–effect relationship between the biological activity and UPLC chromatograms was analyzed by partial least squares regression and gray relational analysis, followed by corresponding validation using isolated components. Finally, network pharmacology and molecular docking were implemented to predict the main antibacterial target components of A. clypearia and the enzyme inhibition active sites of α-amylase and α-glucosidase. P15, P16, and P20 were found to be the antibacterial and antidiabetic active components. The inhibitory effect of 7-O-galloyltricetiflavan (P15) on six bacterial species may be mediated through the lipid and atherosclerosis pathway, prostate cancer, adherens junctions, and targets such as SRC, MAPK1, and AKT1. The molecular docking results revealed that 7-O-galloyltricetiflavan and 7,4′-di-O-galloyltricetiflavan (P16/P20) can bind to α-amylase and α-glucosidase pockets with binding energies lower than −6 kcal/mol. Our study provides guidance for the development of antibacterial and antidiabetic products based on A. clypearia and can be used as a reference for the evaluation of bioactivity of other herbs.

Exosomes act as emerging transdermal drug delivery vehicles with high deformability and excellent permeability, which can be used to deliver various small-molecule drugs and macromolecular drugs and increase the transdermal and dermal retention of drugs, improving the local efficacy and drug delivery compliance. At present, there are many studies on the use of plant exosome-like nanoparticles (PELNVs) as drug carriers. In this review, the source, extraction, isolation, and chemical composition of plant exosomes are reviewed, and the research progress on PELNVs as drug delivery systems in transdermal drug delivery systems in recent years has elucidated the broad application prospect of PELNVs.

Malassezia is a genus of commensal and lipid-dependent yeasts in human skin which also have a pathogenic lifestyle associated with several common skin disorders such as atopic dermatitis and eczema. Symptoms include red, itchy, and inflamed skin. We studied the growth characteristics and biochemical analyses of M. furfur which showed that the protein contents were greater in extracts taken at 24 h. These were then used to infect C57BL/6 mice, resulting in skin rupture. Polygalaxanthone III (POL), a more effective anti-inflammatory ingredient in Polygala japonica Houtt., was applied externally to the ulceration and successfully healed the wounds quickly. POL could not inhibit Malassezia activity as tested by the inhibition zone test, but affected the formation of lipid droplets in HaCaT cells. The wound-healing molecular mechanisms may be involved in the STAT3 pathway according to the Western blot results of skin tissues. Malassezia’s role in skin health is far from certain, and there is no clear solution, so understanding the development of Malassezia-associated skin diseases in general and seeking solutions are very important.