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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. Graphical abstract Key point 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.

Improving the stability of drugs in the gastrointestinal tract and their penetration ability in the mucosal layer by implementing a nanoparticle delivery strategy is currently a research focus in the pharmaceutical field. However, for most drugs, nanoparticles failed in enhancing their oral absorption on a large scale (4 folds or above), which hinders their clinical application. Recently, several researchers have proved that the intestinal epithelial cell membrane crossing behaviors of nanoparticles deeply influenced their oral absorption, and relevant reviews were rare. In this paper, we systematically review the behaviors of nanoparticles in the intestinal epithelial cell membrane and mainly focus on their intracellular mechanism. The three key complex intracellular processes of nanoparticles are described: uptake by intestinal epithelial cells on the apical side, intracellular transport and basal side exocytosis. We believe that this review will help scientists understand the in vivo performance of nanoparticles in the intestinal epithelial cell membrane and assist in the design of novel strategies for further improving the bioavailability of nanoparticles.

Prolonging in vivo circulation has proved to be an efficient route for enhancing the therapeutic effect of rapidly metabolized drugs. In this study, we aimed to construct a nanocrystal-loaded micelles delivery system to enhance the blood circulation of docetaxel (DOC). We employed high-pressure homogenization to prepare docetaxel nanocrystals (DOC(Nc)), and then produced docetaxel nanocrystal-loaded micelles (DOC(Nc)@mPEG-PLA) by a thin-film hydration method. The particle sizes of optimized DOC(Nc), docetaxel micelles (DOC@mPEG-PLA), and DOC(Nc)@mPEG-PLA were 168.4, 36.3, and 72.5 nm, respectively. The crystallinity of docetaxel was decreased after transforming it into nanocrystals, and the crystalline state of docetaxel in micelles was amorphous. The constructed DOC(Nc)@mPEG-PLA showed good stability as its particle size showed no significant change in 7 days. Despite their rapid dissolution, docetaxel nanocrystals exhibited higher bioavailability. The micelles prolonged the retention time of docetaxel in the circulation system of rats, and DOC(Nc)@mPEG-PLA exhibited the highest retention time and bioavailability. These results reveal that constructing nanocrystal-loaded micelles may be a promising way to enhance the in vivo circulation and bioavailability of rapidly metabolized drugs such as docetaxel.

Modifying nanocrystals with functional materials have been common strategy to enlarge the enhancing ability on oral absorption via nanocrystals; however, whether the functional materials have played their full enhancing ability in oral absorption is still unknown. In this study, we synthetized a novel chitosan-based copolymer (the copolymer of sodium dodecyl sulfate (SDS), chitosan (CS) and D-α-Tocopherol polyethylene glycol 1000 succinate, SDS-CS-TPGS), and modified nanocrystals with this copolymer, aiming to enhance the oral absorption of polymer andrographolide (ADR). In real-time distribution study, we found the distribution of ADR, SDS, CS and TPGS varies in gastrointestinal tract, while the distribution of ADR and SDS-CS-TPGS was similar, revealing the SDS-CS-TPGS could able to participate in the absorption process of andrographolide timely. To explore the oral absorption enhancing ability of SDS-CS-TPGS, we prepared a series of nanocrystals modified with different materials and explored their pharmacokinetic performances on SD rats. The results showed the nanocrystals modified with SDS-CS-TPGS (S-C-TANs) exhibited the highest bioavailability, which could enhance the AUC 0-∞ of ADR from 1.291 mg/L*h to 5.275 mg/L*h (enhanced for about 4.09-folds). The enhanced anti- inflammatory efficacy was also found on ICR mice by employing ear swelling rate, TNF-α, IL-1β and IL-6 and pharmacodynamic index. These results indicated that modified with synthesized copolymer containing different functional stabilizers is an efficient strategy to enlarge the enhancing ability on oral absorption of nanocrystals.

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.

GPR119 is a promising target for discovery of anti-type 2 diabetes mellitus agents. We described the optimisation of a novel series of pyrimido[5,4-b][1,4]oxazine derivatives as GPR119 agonists. Most designed compounds exhibited good agonistic activities. Among them, compound 10 and 15 demonstrated the potent EC 50 values (13 and 12 nM, respectively) and strong inherent activities. Moreover, significant hypoglycaemic effect of compound 15 was observed by reducing the blood glucose AUC 0-2h at the dose of 30 mg/kg, which is stronger than Vildagliptin (23.4% reduction vs. 17.9% reduction).

Intestinal lymphatic transport offers an alternative and effective way to deliver drugs, such as avoiding first-pass metabolism, enhancing oral bioavailability, and facilitating the treatment of targeted lymphoid-related diseases. However, the clinical use of luteolin (LUT) is limited by its poor water solubility and low bioavailability, and enhancing lymphatic transport by nanoemulsion may be an efficient way to enhance its oral bioavailability. The objective of this work is to prepare the luteolin nanoemulsions (LUT NEs), optimized its preparation parameters by using Box-Behnken design optimization (BBD) and evaluated it in vitro and in vivo . An Caco-2 / Raji B cell co-incubation monolayer model was established to simulate the M-cell pathway, and the differences in the transmembrane transport of LUT and NEs were compared. Cycloheximide (CHX) was utilized to establish rat chylomicron (CM) blocking model, and for investigating the influence of pharmacokinetic parameters in rats thereafter. The results showed that LUT NEs have good stability, the particle sizes were about 23.87 ± 0.57 nm. Compared with LUT suspension, The P app of LUT NEs was enhanced for 3.5-folds, the oral bioavailability was increased by about 2.97-folds. In addition, after binding with chylomicron, the oral bioavailability of LUT NEs was decreased for about 30% (AUC 0–∞ (μg/L*h): 5.356 ± 1.144 vs 3.753 ± 0.188). These results demonstrated that NEs could enhance the oral absorption of luteolin via lymphatic transport routes. Graphical Abstract

A novel oral drug delivery system, TPGS modified docetaxel proniosomes (DTX-TPGS-PNs), was designed to enhance the oral bioavailability and antitumor efficiency of the poorly water-soluble drug docetaxel. DTX-TPGS-PN niosomes were 93 ± 6.5 nm in size, −18.53 ± 1.65 mV in zeta potential and exhibited spherical morphology, with an encapsulation efficiency of 97.31 ± 0.60%. The system showed sustained release in both simulated gastric and intestinal fluid. The results of caco-2 monolayer, everted gut sac model and improved single-pass intestinal perfusion model transport studies showed that DTX-TPGS-PN niosomes could significantly improve the absorption of DTX. The pharmacokinetics study suggested the absolute bioavailability of DTX-TPGS-PN niosomes were 7.3 times that of DTX solution. In addition, a higher antitumor efficacy than DTX solution was demonstrated in MCF-7 and MDA-MB-231 cells in vitro and in MCF-7 tumor-bearing mice model in vivo . Our results demonstrated DTX-TPGS-PN is promising in enhancing the bioavailability and efficiency of poorly water-soluble drug DTX, and the potential of proniosomes as stable precursors for oral drug delivery.

GPR119 is a promising target for discovery of anti-type 2 diabetes mellitus agents. We described the optimisation of a novel series of pyrimido[5,4-b][1,4]oxazine derivatives as GPR119 agonists. Most designed compounds exhibited good agonistic activities. Among them, compound 10 and 15 demonstrated the potent EC50 values (13 and 12 nM, respectively) and strong inherent activities. Moreover, significant hypoglycaemic effect of compound 15 was observed by reducing the blood glucose AUC0-2h at the dose of 30 mg/kg, which is stronger than Vildagliptin (23.4% reduction vs. 17.9% reduction).GPR119 is a promising target for discovery of anti-type 2 diabetes mellitus agents. We described the optimisation of a novel series of pyrimido[5,4-b][1,4]oxazine derivatives as GPR119 agonists. Most designed compounds exhibited good agonistic activities. Among them, compound 10 and 15 demonstrated the potent EC50 values (13 and 12 nM, respectively) and strong inherent activities. Moreover, significant hypoglycaemic effect of compound 15 was observed by reducing the blood glucose AUC0-2h at the dose of 30 mg/kg, which is stronger than Vildagliptin (23.4% reduction vs. 17.9% reduction).

Staphylococcus aureus colonization and infection occur more commonly among persons living or working in crowded conditions, but characterization of S. aureus colonization within medical communities in China is lacking. A total of 144 (15.4%, 144/935) S. aureus isolates, including 28 (3.0%, 28/935) MRSA isolates, were recovered from the nares of 935 healthy human volunteers residing on a Chinese medical college campus. All S. aureus isolates were susceptible to vancomycin, quinupristin/dalfopristin and linezolid but the majority were resistant to penicillin (96.5%), ampicillin/sulbactam (83.3%) and trimethoprim/sulfamethoxazole (93.1%). 82%, (23/28) of the MRSA isolates and 66% (77/116) of the MSSA isolates were resistant to multiple antibiotics, and 3 MRSA isolates were resistant to mupirocin--an agent commonly used for nasal decolonization. 16 different sequence types (STs), as well as SCCmec genes II, III, IVd, and V, were represented among MRSA isolates. We also identified, for the first time, two novel STs (ST1778 and ST1779) and 5 novel spa types for MRSA. MRSA isolates were distributed in different sporadic clones, and ST59-MRSA-VId- t437 was found within 3 MRSA isolates. Moreover, one isolate with multidrug resistance belonging to ST398-MRSA-V- t571 associated with animal infections was identified, and 3 isolates distributed in three different clones harbored PVL genes. Collectively, these data indicate a high prevalence of nasal MRSA carriage and molecular heterogeneity of S. aureus isolates among persons residing on a Chinese medical college campus. Identification of epidemic MRSA clones associated with community infection supports the need for more effective infection control measures to reduce nasal carriage and prevent dissemination of MRSA to hospitalized patients and health care workers in this community.