Microneedles represent a novel transdermal drug delivery technology that relies on micron-sized needle structures. This approach effectively penetrates the stratum corneum to achieve localized or systemic therapeutic effects, addressing the pain associated with traditional injections and the low bioavailability issues of oral administration. It addresses the pain associated with traditional injections and the low bioavailability of oral administration. Dissolving microneedles have emerged as a research hotspot in microneedle technology due to their distinctive advantages, including dissolvability, ease of operation, and absence of sharp waste. They have garnered widespread attention and application in the pharmaceutical field as an efficient means to enhance transdermal drug absorption. However, many drugs (particularly poorly soluble ones) require higher transdermal absorption enhancement factors, which traditional dissolving microneedles struggle to meet. In light of this, this paper will compare dissolving microneedles with other types of microneedles, propose optimization strategies for dissolving microneedle technology, discuss existing challenges, and outline future research directions, aiming to provide valuable references for the further development of dissolving microneedles.

ABSTRACT Atherosclerotic cardiovascular disease (AS) remains a leading global health concern. In this study, we investigated a macrophage‐derived exosome‐based delivery system for puerarin (Pue). The isolated vesicles were characterized by transmission electron microscopy, particle‐size and zeta‐potential analysis, and Western blot validation of extracellular vesicle‐associated markers, including CD63, CD9, CD81, TSG101, and Alix, together with Calnexin as an endoplasmic‐reticulum‐associated negative/depletion marker. In vitro experiments showed that exosome‐based delivery enhanced cellular uptake of puerarin and was associated with reduced oxidative‐stress‐related signals, decreased macrophage migratory activity, and reduced foam‐cell‐related readouts under the tested conditions. In vivo studies using an ApoE−/− mouse model showed that Pue–Exos reduced aortic plaque burden, promoted collagen deposition, and improved serum lipid‐related indices. No obvious histopathological abnormalities were observed in major organs after treatment, suggesting preliminary in vivo tolerability. Mechanistic evaluation in C57BL/6 mice showed that treatment was associated with increased expression of HIF‐1α, NF‐κB, IL‐6, IL‐1β, CD68, and α‐SMA under the present experimental conditions. Therefore, these findings are more appropriately interpreted as inflammation‐associated signaling changes and remodeling‐related responses, rather than definitive evidence of a uniformly suppressed inflammatory state or a confirmed anti‐atherosclerotic mechanism. Taken together, these results suggest that macrophage‐derived exosome‐based delivery may improve the performance of puerarin in atherosclerosis‐related experimental settings, although the underlying mechanism requires further clarification.

Compared with small-molecule drugs, macromolecular drugs offer advantages such as high safety, strong specificity, and low immunogenicity. Although macromolecular drugs suffer from inherently low bioavailability and face multiple physiological barriers, a systematic review that comprehensively summarizes the strategies to overcome these challenges is still lacking. Therefore, developing effective strategies to enhance the bioavailability of macromolecular drugs represents a highly promising research direction. Numerous studies have shown that macromolecular drugs prepared through biotechnology can be used in combination with various biological carriers to activate the immune system by inducing the production of immune cells and immune factors, thereby achieving disease prevention and treatment. This article reviews the multiple absorption barriers encountered by macromolecular drugs, such as peptides and proteins, in different delivery systems, as well as the strategies to improve their bioavailability and the technical approaches to overcome the related delivery challenges, aiming to provide theoretical references and a foundation for the design of novel macromolecular drug delivery systems.

Tight junctions (TJs), a critical regulator of intestinal barrier integrity, has gained increasing attention on fields like intestinal health and drug absorption. Recent researches highlighted the remarkable potential of natural plants on intestinal TJs through multiple mechanisms. This review selected several represented active components derived from natural medicinal plants (like flavonoids, saponins, alkaloids, and etc.) and formulas of traditional Chinese medicine (TCM), and systematically reviewed their mechanisms on modulating intestinal TJs, including the modulation of inflammatory responses, upregulation of tight junction proteins (TJPs) expression and promotion of intestinal epithelial cell repair. Furthermore, their potential applications in fields like management of intestinal disorders management and oral absorption are discussed. This review could provide novel perspectives and theoretical support on intestinal TJs related researches.

Oral drugs classified under Class III of the Biopharmaceutics Classification System (BCS) are defined by high aqueous solubility yet low intestinal permeability. Their restricted oral bioavailability arises not from inadequate dissolution, but is primarily governed by the intestinal permeability barrier, coupled with substantial inter-individual variability in absorption. This review adopts the intestinal permeability barrier as its core analytical framework to dissect the key determinants of oral absorption for BCS III drugs, while presenting a comparative and critical evaluation of prevailing bioavailability enhancement strategies. From perspectives including mechanism of action, achievable magnitude of enhancement, applicable physicochemical and physiological conditions, and translational feasibility, the intrinsic mechanistic limitations and applicable boundaries of distinct strategies are delineated. Finally, this paper concludes that the absorption barriers of BCS III drugs cannot be universally surmounted by a single strategy, emphasizing the significance of mechanism-guided strategy selection for the rational design of oral drug delivery systems. In doing so, it provides a foundational basis for the rational development of oral delivery systems tailored to BCS III drugs.

Central nervous system diseases (CNSDs) pose a significant therapeutic challenge, largely due to the restrictive blood-brain barrier (BBB). While nanocarriers like liposomes, polymeric nanoparticles, and exosomes have been explored for brain delivery, carbon dots (CDs) have emerged as a particularly promising platform. These carbon-based nanomaterials offer advantages such as small size, excellent biocompatibility, and versatile surface chemistry, enabling precise functionalization. Compared to liposomes and polymer nanoparticles, CDs exhibit superior size uniformity, photophysical properties, and chemical stability. Unlike exosomes, they are synthetically controllable, scalable for mass production, and amenable to precise surface modification. A key advantage lies in their ability to cross the BBB via specific molecular mechanisms, such as receptor‑mediated transcytosis, when conjugated with targeting ligands (e.g., transferrin, lactoferrin, or cell‑penetrating peptides). This allows for disease-specific targeting, for instance, of amyloid-β plaques in Alzheimer's or overexpressed receptors in brain tumors. CDs can serve as intrinsic therapeutics or as drug carriers. However, their clinical translation depends on addressing critical issues of long-term safety, potential neurotoxicity (such as inducing oxidative stress and inflammation), and biodegradability. This review systematically summarizes the synthesis methods and functionalization strategies of CDs, alongside the molecular mechanisms underlying their BBB penetration. It focuses on their therapeutic potential for CNSDs, providing a comparative analysis with other common nanocarriers. Furthermore, it evaluates the current research and improvement strategies concerning CDs toxicity, biocompatibility, and long-term safety. Finally, the review outlines ongoing challenges and future directions for the field.

The tumor-targeted drug delivery system (TTDNS) uses nanocarriers to transport chemotherapeutic agents to target tumor cells or tissues precisely. This innovative approach considerably increases the effective concentration of these drugs at the tumor site, thereby enhancing their therapeutic efficacy. Many chemotherapeutic agents face challenges, such as low bioavailability, high cytotoxicity, and inadequate drug resistance. To address these obstacles, TTDNS comprising natural polysaccharides have gained increasing popularity in the field of nanotechnology owing to their ability to improve safety, bioavailability, and biocompatibility while reducing toxicity. In addition, it enhances permeability and allows for controlled drug delivery and release. This review focuses on the sources of natural polysaccharides and their direct and indirect mechanisms of anti-tumor activity. We also explored the preparation of various polysaccharide-based nanocarriers, including nanoparticles, nanoemulsions, nanohydrogels, nanoliposomes, nanocapsules, nanomicelles, nanocrystals, and nanofibers. Furthermore, this review delves into the versatile applications of polysaccharide-based nanocarriers, elucidating their capabilities for in vivo targeting, controlled release, and responsiveness to endogenous and exogenous stimuli, such as pH, reactive oxygen species, glutathione, light, ultrasound, and magnetic fields. This sophisticated design substantially enhances the chemotherapeutic efficacy of the encapsulated drugs at tumor sites and provides a basis for preclinical and clinical research. However, the in vivo stability, drug loading, and permeability of these preparations into tumor tissues still need to be improved. Most of the currently developed biomarker-sensitive polysaccharide nanocarriers are still in the laboratory stage, more innovative delivery mechanisms and clinical studies are needed to develop commercial nanocarriers for medical use.

Cryptotanshinone (CTS), an antiplatelet compound from Salvia miltiorrhiza, exhibits in vitro potency comparable to aspirin. This study integrated network pharmacology and metabolomics to elucidate its underlying mechanisms. An acute blood stasis model was induced in Sprague-Dawley rats using epinephrine and ice-water immersion. Animals were assigned to seven groups. Platelet aggregation was measured turbidimetrically using arachidonic acid (AA) and adenosine diphosphate (ADP) as agonists. Core targets were predicted by network pharmacology, differential metabolites were screened, and pathways were enriched using untargeted metabolomics. Integrated analysis identified shared pathways and key targets, validated by molecular docking. AA- and ADP-induced aggregation was significantly increased in model rats versus the blank group. CTS at all doses markedly inhibited aggregation in a dose-dependent manner. Network pharmacology identified 15 core targets. Metabolomics identified 51 differential metabolites enriched in seven pathways, including glycerophospholipid and butanoate metabolism. Integrated analysis revealed five common pathways: linoleic acid metabolism, arginine biosynthesis, AA metabolism, glutathione metabolism, and drug metabolism—and four key targets (CYP3A4, NOS3, PTGS2, and GSTP1). Molecular docking showed strong binding energies (<−9 kcal/mol) between CTS and these targets. CTS inhibits platelet aggregation by regulating CYP3A4, NOS3, PTGS2, and GSTP1 and intervening in five metabolic pathways, supporting its potential as an anti-platelet agent.

Background/Objectives: Achyranthes bidentata (AB), recognized as a food and traditional Chinese medicine, exhibits notable biological activity. Our previous study showed the hypoglycemic effect of Achyrantha bidentata polysaccharide (ABP). The properties and digestion process of polysaccharides affect their pharmacological activities. The digestion characteristics of ABP are unclear. In this study, we aimed to explore the characteristics of ABP’s simulated digestion and its prebiotic properties and hypoglycemic effects. Methods: We used simulated digestion methods to investigate the alterations in ABP levels in the process of digestion and fermentation. Animal experiments were used to compare the effects of the prebiotic properties of ABP on normal control (NC) and type 2 diabetes mellitus (T2DM) mice. Then, in order to further verify the hypoglycemic effect of ABP after fermentation (ABPF), α-glucosidase activity and glucose uptake in Caco-2 cells were examined. Results: The results showed that ABP was anti-digestive and mainly degraded by the intestinal flora. Moreover, ABP showed a stronger promoting advantage against beneficial bacteria and inhibited harmful bacteria in the T2DM mice. Compared with NC mice, after ABP treatment, T2DM mice showed a higher increase in levels of short-chain fatty acids (SCFAs). Additionally, the glucose uptake and α-glucosidase activity of Caco-2 cells were significantly decreased after treatment with ABPF. Conclusions: These results underscore the potential of ABP as a prebiotic candidate for gut health promotion and T2DM alleviation.

Atherosclerosis is a complex cardiovascular disease driven by multiple factors, including aging, inflammation, oxidative stress, and plaque rupture. The progression of this disease is often covert, emphasizing the need for early biomarkers and effective intervention measures. In recent years, advancements in therapeutic strategies have highlighted the potential of targeting specific processes in atherosclerosis, such as plaque localization, macrophage activity, and key enzymes. Based on this, this review discusses the potential role of targeted drugs in the treatment of atherosclerosis. It also focuses on their clinical efficacy in anti-atherosclerosis treatment and their ability to provide more precise therapeutic approaches. The findings underscore that future research can concentrate on exploring newer drug delivery systems and biomarkers to further refine clinical treatment strategies and enhance the long-term dynamic management of atherosclerosis. 1. Forming mechanisms of atherogenesis. 2. Impact of nanomedicines on atherosclerotic cancer patients: a systematic review. 3. Protective potential of immunity against atherosclerotic targets: a case-control study. 4. G3BP2 peptide immunization against atherosclerosis: a randomized controlled trial.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by synovial hyperplasia and joint destruction. Previous studies have demonstrated that the alkaloids of Rushanhu (ARSHs), the dried root and stem of Zanthoxylum nitidum var. tomentosum, exhibit favorable therapeutic effects on RA, and this study aims to investigate the underlying molecular mechanisms involved. Methods: A complete Freund’s adjuvant (CFA)-induced arthritis model in male SD rats (n = 64) was used to evaluate ARSHs. Groups included control, model, methotrexate (MTX), and ARSH-treated. Therapeutic effects were assessed via arthritis index, paw swelling, and serum cytokines (IL-1β, IL-6, IL-17A). Network pharmacology identified bioactive alkaloids and core targets, validated by molecular docking. In vitro mechanisms (proliferation, apoptosis, signaling pathways) were examined in MH7A synovial cells. Results: ARSHs significantly attenuated joint inflammation and damage in CFA rats (* p < 0.01 vs. model), reducing pro-inflammatory cytokines. Fifteen alkaloids (e.g., dihydrochelerythrine, magnoflorine) and 24 targets (e.g., SRC, STAT3, MAPK3) were prioritized. Molecular docking confirmed strong binding (binding energy < −7.0 kcal/mol). In vitro, ARSHs suppressed MH7A proliferation and induced apoptosis via Bcl-2/Bax dysregulation and the inhibition of SRC/STAT3/MAPK3 phosphorylation. Conclusions: ARSHs mitigate RA pathogenesis by targeting the SRC/STAT3/MAPK3 signaling axis in synovial cells. This study provides mechanistic validation of ARSHs as multi-target phytotherapeutic agents against inflammatory arthritis.

Background and aim: Pulsatilla saponin (Ps) was isolated from Pulsatilla chinensis (Bunge) Regel, a traditional Chinese medicine, that has anti-proliferation, anti-inflammation, anti-tumor and immunomodulation activities. However, the anti-psoriasis activity of Ps and its underlying mechanisms have not been fully elucidated. This study aims to investigate the effect and potential mechanisms of Ps on psoriasis. Experimental procedure: Ps underwent quality control through HPLC and NMR analysis. Wound healing assay, MTT, clone assay, and EdU staining were used to detect HaCaT cells proliferation. Western blot and immunofluorescence were used to assess the expression of proteins. The th17 cells population was analyzed by flow cytometry. The levels of cytokines in the mice skin tissues were measured by RT-qPCR and ELISA. Results and conclusion: In vitro, Ps has an inhibition effect on the proliferation of M5-induced HaCaT cells. Ps inhibited proliferation by regulating NF-kappa B and JAK1/STAT3 pathways. Additionally, Ps decreased TNF-alpha, IL-1R, and IL-6 mRNA levels in M5-induced HaCaT cells. In vivo, Ps improved the pathological damage of Imiquimod (IMQ)-induced psoriasis BALB/c mice skin and reduced the Ki67 level in mice skin tissue. Further results showed that Ps decreased Th17 cells differentiation and IL-22, IL-17A, IL-6, IFN-gamma, TNF-alpha, and IL-1R secretion. Ps could ameliorate the psoriatic symptoms, decrease M5-induced HaCaT cell proliferation, and decrease the differentiation of Th17 cells in IMQ-induced psoriasis mice. Ps suppressed the release of inflammation cytokines by regulating NF-kappa B and JAK1/STAT3 pathways. Those results indicate that Ps has promising therapeutic potential for psoriasis treatment.

Oral administration remains the most prevalent route of drug delivery due to its non-invasive nature and excellent patient compliance. However, the suboptimal bioavailability of many orally administered drugs poses a significant challenge, which can be attributed to complex absorption mechanisms involving factors such as solubility, permeability, first-pass metabolism, and efflux transporter effects. Consequently, exploring effective strategies to enhance oral drug absorption has become a major research focus. Among these, the prodrug approach has garnered significant attention for its versatility in optimizing drug properties. This article systematically reviews recent research progress in improving the oral bioavailability of drugs based on the prodrug strategy. It focuses on enhancing drug solubility, permeability, and metabolic stability through prodrug design, leveraging gastrointestinal transporter- mediated absorption mechanisms, and combining formulation strategies to further improve oral drug absorption. The aim is to provide a theoretical foundation and strategic support for related research and applications in this field.

To investigate the therapeutic benefits and possible mechanism of total flavonoids of Litchi chinensis Sonn. seed (TFLS) on hepatic fibrosis (HF) in vivo and in vitro. A carbon tetrachloride (CCl4)-induced rat HF model and transforming growth factor β1 (TGF-β1)-stimulated hepatic stellate cell (HSC)-T6 cells were employed. For in vivo study, rats were randomly divided into 6 groups using a random number table method, including vehicle, CCl4, silybin (50 mg/kg), and low-, medium-, high-dose (25, 50, and 100 mg/kg) TFLS treatment groups. TFLS or silybin was administered daily by gavage for 8 weeks during CCl4 induction period. For in vitro study, HSC-T6 cells were divided into 4 groups, including control, TGF-β1 (20 ng/mL), TGF-β1 + Z-DNA binding protein 1 (ZBP1) siRNA (si-ZBP1), TGF-β1 + low-dose (80 µg/mL) TFLS, and TGF-β1 + high-dose (160 µg/mL) TFLS groups. Serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST), hydroxyproline (HYP), total bile acid (TBA), interleukin (IL)-1β, IL-18, IL-6, and tumor necrosis factor (TNF)-α were measured using enzyme-linked immunosorbent assay. Hematoxylin-eosin and Masson’s trichrome staining were employed to conduct a histological examination of the liver tissue. Apoptosis was assessed by TUNEL. Cysteine-aspartic acid protease (CASP)-8, NLR family pyrin domain containing 3 (NLRP3), gasdermin D (GSDMD), and receptor-interacting protein kinase (RIPK) 3 were immunohistochemically detected. CASP-8, NLRP3, GSDMD, CASP-3, BCL-2, BCL-2-associated X (BAX), ZBP1, RIPK1, and RIPK3 mRNA levels were measured by quantitative real-time polymerase chain reaction. PANoptosis-related proteins were detected by Western blot. In CCl4-induced HF rats, TFLS improved liver function, inflammatory response, and liver tissue fibrosis (P<0.05 or P<0.01). TFLs inhibited the activation of PANoptosis initiator ZBP1, which subsequently regulated PANoptosis by increasing BAX, CASP-3, CASP-8 and decreasing BCL-2, NLRP3, GSDMD, CASP-1, RIPK1, RIPK3, and mixed lineage kinase domain-like expressions (P<0.05 or P<0.01). In vitro, TFLS inhibited TGF-β1-induced HSC-T6 cells activation and PANoptosis (P<0.05 or P<0.01). TFLS might ameliorate HF by targeting ZBP1 to suppress PANoptosis, highlighting its multi-modal regulation of apoptosis, pyroptosis, and necroptosis.

Traditional chemical analysis methods for evaluating the quality of traditional Chinese medicine (TCM), such as Cortex fraxini ( C. fraxini), often fail to comprehensively address spectrum-effect, dose-effect, and toxicity-effect relationships, limiting their ability to predict clinical efficacy and safety. To overcome this challenge, this study introduces the effect-constituent index (ECI), a novel metric integrating multidimensional chemical composition data and bioactivity-based weighting strategies for holistic quality assessment. Focusing on the antioxidant properties of C. fraxini, we established a high-performance liquid chromatography (HPLC) fingerprint profile to quantify four key bioactive components (esculin, fraxin, esculetin, and fraxetin) and evaluated their antioxidant capacities via 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2 '-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical-scavenging assays. The ECI framework revealed significant variability in antioxidant potential across 38 batches, with batches S13, S16, and S11 exhibiting the highest DPPH-and ABTS-based ECI values, while S10, S35, and S14 consistently ranked lowest. Validation experiments confirmed a strong correlation between calculated ECI values and experimentally determined antioxidant activities, although certain batches (e.g., S11, S13, S15, S16) demonstrated higher measured bioactivity than predicted. This study successfully bridges chemical composition with therapeutic efficacy by establishing concentration-effect relationships for active constituents, offering a robust and innovative tool for advancing quality control paradigms in herbal medicine. The ECI model provides a scientific foundation for optimizing the safety, efficacy, and standardization of TCM.

Andrographis paniculata is a plant of the Acanthaceae family and its primary bioactive constituent, andrographolide, exhibits a broad spectrum of pharmacological activities and notable clinical efficacy. However, its poor solubility and limited bioavailability pose significant challenges for therapeutic applications. To overcome these limitations, researchers have synthesized andrographolide sulfonates by reacting andrographolide with ethanol and sulfuric acid. This sulfonated derivative significantly enhances water solubility and bioavailability while retaining key pharmacological properties such as anti-inflammatory and antiviral activities. As a representative formulation, Xiyanping injection has been widely employed in the treatment of respiratory infections, pneumonia, and related conditions, playing a critical role during the COVID-19 pandemic. Despite its widespread application, there has yet to be a comprehensive review of its chemical composition and pharmacological mechanisms. Additionally, the safety of Xiyanping injection remains a topic of some debate. This review systematically examines the chemical composition, pharmacological activities, clinical applications, and adverse reactions of andrographolide sulfonates and their formulation in Xiyanping injection to provide a scientific basis for further research and applications, while also offering valuable insights for the development of similar sulfonated drugs.

Utilizing transporter-mediated drug delivery to achieve effective oral absorption emerges as a promising strategy. Researchers have been concentrated on discovering solutions to the issues of low solubility and poor permeability of insoluble drugs, whereas, current reports have revealed that drug transporter proteins are abundantly expressed in the mucosa of intestinal epithelial cells, and that their mediated drug absorption effectively improved the bioavailability of orally administered drugs. There are two main categories based on the transporter mechanism, which include the family of ATP-binding cassette (ABC) transporters with efflux effects that reduce drug bioavailability and the family of solute carriers (SLC) transporters with uptake effects that promote drug absorption, respectively. Thus, we review studies of intestinal transporter-mediated delivery of drugs to enhance oral absorption, including the types of intestinal transporters, distribution characteristics, and strategies for enhancing oral absorption using transporter-mediated drug delivery systems are summarized, with the aim of providing important theoretical references for the development of intestinal-targeted delivery system.

Yan Huanglian is the whole grass and rhizome of Corydalis saxicola Bunting (CSB) of the Papaveraceae family. CSB has various pharmacological effects and is a promising ethnopharmaceutical. The chromatographic fingerprint of 16 batches of CSB samples was established in this study. Quantitative analysis of multi-components by single marker and the external standard method (ESM) was used to quantitatively assess seven constituents of CSB. Because of its high stability and availability, dehydrocavidine was used as a reference to determine the relative correction factors (RCFs) of columbamine, epiberberine, coptisine hydrochloride, palmatine chloride, berberine hydrochloride, and chelerythrine based on high-performance liquid chromatography. The calculated quantitative analysis of multi-components by single marker values is consistent with those obtained from the ESM, and the repeatability of the RCFs was demonstrated. For the first time, the quantitative analysis of multi-components by the single marker method has been established for the simultaneous determination of seven components, and it is demonstrated to be feasible and accurate for the quality evaluation of CSB combined with chromatographic fingerprint analysis. The combination of these methods could be used as a reference for quality control in Chinese medicine.

Many researchers have studied the oral absorption mechanisms yet, however, considering stabilizers often participate in the absorption process of nanocrystals, these known mechanisms may be incorrect. Hence in this study, we aimed to explore the correct absorption mechanism of nanocrystals by performing related studies on stabilizer-free nanocrystals. We firstly prepared stabilizer-free silymarin nanocrystals by high-pressure homogenization, and then performed absorption-related studies, such as solubility, dissolution rate, pharmacokinetic study, cellular uptake and intracellular transport. Results showed the stabilizer-free silymarin nanocrystals had an average particle size of (450.2 +/- 4.46) nm, with PDI of 0.280 +/- 0.021 and Zeta potential of -26.9 +/- 2.4 mV. The conversion of silymarin crude drug to stabilizer-free silymarin nanocrystals increased the compound's solubility by 1.41 times, with a dissolution rate of 92.2 % in water within 30 min compared to 38.5 % for crude drugs. Pharmacokinetic studies showed the oral bioavailability of stabilizer-free silymarin nanocrystals was found to be 1.48 times greater than that of the crude drugs. The cell experimentation results demonstrated that the stabilizer-silymarin nanocrystals can improve uptake but have poor transmembrane transport properties. Most researchers believe that nanocrystals can enhance transmembrane transport of drugs via an endocytosismediated pathway. In fact, nanocrystals are indeed endocytosed more by the cells, but this transport pathway is poor because the cells lack the intracellular transport pathway to transport nanocrystals from the AP side to the BP side. Therefore, we believe that the intracellular transport of nanocrystals can be enhanced by modifications and other carriers if needed to improve nanocrystals' ability to promote oral absorption.

Oral administration is the most acceptable route of drug delivery at this stage due to its convenience, safety, and non-invasiveness. However, drugs given orally are exposed to a complex gastrointestinal environment, causing a tremendous challenge for their successful absorption into the circulation. Over the past decades, researchers have developed various novel pharmaceutical technologies to improve oral absorption, among which the vesicular drug delivery system (like liposomes, niosomes and transfersomes) has received extensive attention. Encouragingly, there have been several investigations confirming the improved effect of vesicular drug delivery systems on oral drug absorption. Nevertheless, the clinical translation of oral vesicular drug delivery systems has been less impressive than implied by the positive results, and few vesicular formulations for oral use have been marketed yet. Against this background, this article provides an overview of the current applications and challenges associated with the vesicular delivery systems available for oral drug delivery, specifically liposomes, niosomes, transfersomes, chitosomes and bilosomes. The composition, formation mechanism, drug delivery advantages and application cases of these carriers in oral drug delivery are summarized. The possible mechanisms by which vesicular carriers enhance oral drug absorption are analyzed in terms of the in vivo process of oral drugs. Further, the challenges that oral vesicular carriers now face, such as safety, undefined in vivo fate, and scale-up production, are summarized, while possible strategies to deal with them are indicated. By reviewing the aforementioned, it can facilitate a more comprehensive knowledge of vesicular systems that can be used for oral drug delivery, providing a theoretical basis and reference for the design of oral formulations.