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Oral probiotics have significant potential for preventing and treating many diseases. Yet, their efficacy is often hindered by challenges related to survival and colonization within the gastrointestinal tract. Nanoparticles emerge as a transformative solution, offering robust protection and enhancing the stability and bioavailability of these probiotics. This review explores the innovative application of nanoparticle-armored engineered probiotics for precise disease treatment, specifically addressing the physiological barriers associated with oral administration. A comprehensive evaluation of various nano-armor probiotics and encapsulation methods is provided, carefully analyzing their respective merits and limitations, alongside strategies to enhance probiotic survival and achieve targeted delivery and colonization within the gastrointestinal tract. Furthermore, the review explores the potential clinical applications of nano-armored probiotics in precision therapeutics, critically addressing safety and regulatory considerations, and proposing the innovative concept of 'probiotic intestinal colonization with nano armor' for brain-targeted therapies. Ultimately, this review aspires to guide the advancement of nano-armored probiotic therapies, driving progress in precision medicine and paving the way for groundbreaking treatment modalities. [ABSTRACT FROM AUTHOR]

Background & Problems: Oral administration is the most common mode of medical treatment for pediatric patients. Although over 98% of the patients in the targeted pediatric unit require oral medication, the oral administration adherence rate in 2022 was 43.9%. The reasons for this low rate were identified as: (1) no relevant oral administration educational materials, (2) no relevant continued nursing education provided, and (3) lack of assistive tools and feeding aids to help administer oral medication to young children. Purpose: This project was developed to increase the adherence rate of oral administration of preschool pediatric inpatients in our hospital. Resolutions: The improvement strategies included the design of patient-centered oral medication care guidance leaflets and QR code (quick response code) video links, the development of therapeutic play aids, adding cartoon characters to medicine feeders, and the creation of a "Rescue the Forest" picture book and video and reward stickers. Results: The oral medication adherence rate increased from 43.9% pretest to 91.9% posttest. Conclusion: This project and its positive effect on the rate of oral medication adherence may be referenced by other pediatric units. [ABSTRACT FROM AUTHOR]

Solid lipid nanoparticles (SLNs) have gained interest as drug delivery carriers due to their efficient cellular internalization and increased therapeutic effect of the loaded drug, with minimal side effects. Although recently several studies have shown the possibility to administer SLNs during pregnancy to vehicle mRNA to the placenta, data about the effect of premating exposure to SLNs on pregnancy outcome are scant. Considering that assumption of drug-delivering nanocarriers in reproductive age may potentially affect women's reproductive health, the aim of the present study was to evaluate whether repeated oral administration of SLNs to female mice prior to mating would influence key pregnancy outcomes. For this purpose, SLNs melatonin loaded (SLN + mlt) or unloaded were orally administered to CD1 female mice at two different dosages—low (7.5 mg/kg) and high (750 mg/kg) —three times a week for 6 weeks. Females mice were mated and pregnancy was monitored from conception to delivery. All the assessed pregnancy parameters, including time to pregnancy, pregnancy duration, litter size, and the presence of any gross anomalies in the pups, and maternal key biochemical parameters were not significantly affected by SLN administration. Embryonic development was also evaluated and no effects on the number of implantation sites, fetus numbers, incidence of fetal resorptions, and measurements of crown-rump length, as well as fetal and placental weights, were observed in the treated mothers. The impact of SLNs on maternal intestinal barrier integrity and inflammation was assessed both in vivo in mice and in vitro using an intestinal epithelial barrier model by qRT-PCR. Results showed that unloaded SLNs, but not the SLN + mlt, affected intestinal barrier integrity. Although variation in the expression of inflammatory cytokines was recorded, this did not reflect in significant histological alterations and the integrity of the intestinal barrier was maintained. The in vitro model further confirmed the biocompatibility of SLNs, showing that both loaded and unloaded SLNs did not affect the integrity of the simulated intestinal epithelial barrier. In conclusion, these data suggest that administering SLNs, as a drug delivery vehicle, prior to conception does not affect either maternal health or fetal development, posing no risk to future pregnancy. [ABSTRACT FROM AUTHOR]

Metal–organic framework (MOF) is a porous material composed of metal ions/clusters and organic ligands. It has attracted much attention due to its high specific surface area, good biocompatibility, chemical modifiability, and diversity of components. Among many MOFs, zirconium‐based MOFs are particularly suitable for biological applications due to their optimal stability and low toxicity to hydrolysis. However, due to the weak coordination bonds between many metal clusters and organic ligands, most MOFs are prone to collapse in acidic environments, and the stability of MOFs as drug carriers cannot be guaranteed so that they cannot be widely used as oral drug carriers. This study synthesized the three MOFs using metal Zr ion clusters as the center and different nitrogen‐containing organic ligands, which are stable in gastric acid, namely, UiO‐66‐PDC, UiO‐66‐NH2, and UiO‐66‐NO2. The anionic drug loxoprofen (LOX) was loaded and characterized using scanning electron microscopy, infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and x‐ray diffraction. The adsorption and release behaviors of LOX and the three MOFs were studied from the molecular point of view by computer simulation. A series of behaviors and mechanisms of pH‐responsive nitrogen‐containing MOFs as oral drug carriers were further explored through rat pharmacokinetic experiments, the everted gut sac experiments, and intestinal absorption mechanism experiments. The experimental results show that there is a strong electrostatic interaction between anionic drug LOX and UiO‐66‐PDC under simulated gastric acid environment, which prolongs the half‐life of the drug, proving that LOX@UiO‐66‐PDC is a promising new oral drug delivery system. [ABSTRACT FROM AUTHOR]

Background/Aim: Salmonella typhimurium A1-R (A1-R) targets and inhibits a wide range of cancer types without continuously infecting healthy tissue. Chloroquine, an antimalarial drug, induces apoptosis and inhibits autophagy in cancer cells. The aim of the present study was to determine the synergy of A1-R plus chloroquine on HT1080 human fibrosarcoma cells in vitro and in a nude-mouse model. Materials and Methods: HT1080 human fibrosarcoma cells were used for in vitro experiments. Four groups were analysed in vitro: No-treatment control; A1-R; chloroquine; A1-R plus chloroquine. The nude-mouse models of HT1080 human fibrosarcoma were randomly assigned into four groups: G1: untreated control; G2: Oral A1-R [5×107 colony forming units (CFU)/body, twice a week, 2 weeks]; G3: Chloroquine [100 mg/kg/body, intraperitoneal (IP) administration, twice a week, 2 weeks]; G4: Oral A1-R (5×107 CFU/body), twice a week, 2 weeks plus chloroquine (100 mg/kg/body, IP), twice a week, 2 weeks. Each cohort consisted of five mice. Tumor volume and body weight were assessed biweekly. Results: A1-R combined with chloroquine synergistically decreased the viability of HT1080 cells in vitro compared to other groups. Orally-administered A1-R at 5×107 CFU combined with IP-administered chloroquine eradicated HT1080 tumors in nude mice, without body-weight decrease. Conclusion: The combination treatment of A1-R plus chloroquine demonstrated synergy against HT1080 cancer cells in vitro and in vivo. A1-R was administered orally, suggesting its potential as a probiotic. The present results suggest the clinical potential of the combination of A1-R and chloroquine for soft-tissue sarcoma therapy, a recalcitrant disease. [ABSTRACT FROM AUTHOR]

BackgroundCommercial foot-and-mouth disease (FMD) vaccines have several drawbacks, including a short duration of the immune response after vaccination and local adverse reactions at the vaccination site. Therefore, we developed a new vaccination strategy that simultaneously improves the health status of the host and stimulates systemic immunity by combining the oral administration of glycyrrhizic acid (GA) and intramuscular injection of the FMD vaccine.MethodsWe evaluated the efficacy of the oral immune enhancer GA in conjunction with an intramuscular injection of the FMD vaccine. After vaccination, the experimental (mice) and target animals (pigs) were orally administered GA daily for 4 weeks and once a week for the next 4 weeks. Subsequently, we evaluated safety using various biochemical serum assays, the efficacy of inducing immune responses using serological assays, and the expression of genes related to systemic immunity induction.ResultsOral administration of GA in combination with an intramuscular injection of the FMD vaccine enhanced early, mid-term, and long-term immunity in experimental and target animals. We also confirmed that this co-administration increased the expression of secretory IgA (sIgA), an important indicator of mucosal immunity. Additionally, significant gene elevations in systemic immune markers along with T helper (Th) immune responses were observed.ConclusionThese findings suggest that combining the oral administration of GA with the intramuscular injection of an inactivated FMD vaccine can induce a potent and sustained immune response and stimulate the systemic immune system by promoting sIgA and cytokine gene expression. Our research can be used to enhance the efficacy of existing commercial vaccines as well as control other animal diseases by improving the host’s immune system.

Pain management in horses plays a pivotal role in the therapeutic approach to several diseases. Horses have cannabinoid receptors at the level of dorsal root ganglia, blood vessels, and synoviocytes that can be up or down- regulated by inflammatory conditions, justifying the possible efficacy of exogenous cannabinoids (i.e., phytocannabinoids) in managing several painful pathologies in this animal species. However, the current use of supplements containing cannabidiol (CBD) in equines is based on anecdotal evidence, without the support of sufficient pharmacokinetic studies. In humans, the concentration peak of CBD and the area under the concentration-time curve (AUC) are both strongly influenced by food administration. Also, in equids, the oral bioavailability of some drugs can be influenced by the meal but no information is available about CBD. This study investigated the pharmacokinetics of CBD following single oral administration of two different formulations of pure CBD (oil and paste), dosed at 1 mg/kg, at two different times about food administration. CBD oil and CBD paste were administered orally at 1 mg/kg to eight healthy horses according to a cross over design, and blood samples were taken at pre-fixed time-points for the pharmacokinetic analyses. The obtained pharmacokinetic data did not allow for statistically significant differences between formulations (paste or oil) and feeding time (fed and fasted status). However, following treatment with the paste, the Cmax was achieved in a shorter time range compared to the oily formulation, indicating that it could be a better formulation to consider in future equine studies.

Solid lipid nanoparticles (SLNs) have gained interest as drug delivery carriers due to their efficient cellular internalization and increased therapeutic effect of the loaded drug, with minimal side effects. Although recently several studies have shown the possibility to administer SLNs during pregnancy to vehicle mRNA to the placenta, data about the effect of premating exposure to SLNs on pregnancy outcome are scant. Considering that assumption of drug-delivering nanocarriers in reproductive age may potentially affect women’s reproductive health, the aim of the present study was to evaluate whether repeated oral administration of SLNs to female mice prior to mating would influence key pregnancy outcomes. For this purpose, SLNs melatonin loaded (SLN + mlt) or unloaded were orally administered to CD1 female mice at two different dosages—low (7.5 mg/kg) and high (750 mg/kg) —three times a week for 6 weeks. Females mice were mated and pregnancy was monitored from conception to delivery. All the assessed pregnancy parameters, including time to pregnancy, pregnancy duration, litter size, and the presence of any gross anomalies in the pups, and maternal key biochemical parameters were not significantly affected by SLN administration. Embryonic development was also evaluated and no effects on the number of implantation sites, fetus numbers, incidence of fetal resorptions, and measurements of crown-rump length, as well as fetal and placental weights, were observed in the treated mothers. The impact of SLNs on maternal intestinal barrier integrity and inflammation was assessed both in vivo in mice and in vitro using an intestinal epithelial barrier model by qRT-PCR. Results showed that unloaded SLNs, but not the SLN + mlt, affected intestinal barrier integrity. Although variation in the expression of inflammatory cytokines was recorded, this did not reflect in significant histological alterations and the integrity of the intestinal barrier was maintained. The in vitro model further confirmed the biocompatibility of SLNs, showing that both loaded and unloaded SLNs did not affect the integrity of the simulated intestinal epithelial barrier. In conclusion, these data suggest that administering SLNs, as a drug delivery vehicle, prior to conception does not affect either maternal health or fetal development, posing no risk to future pregnancy.

Extracellular vesicles (EVs) are nanoscale phospholipid-based particles secreted by cells and are essential mediators responsible for intercellular signal communication. The rapid development of EV nanotechnology has brought unprecedented opportunities for nanomedicine. Among various administration methods, oral administration is the most convenient and simplest. However, most drugs (peptides, small molecule drugs, nucleic acids, and therapeutic proteins) greatly reduce their oral bioavailability due to the harsh gastrointestinal environment. Notably, some EVs have been shown to cross biological barriers, including the gastrointestinal tract. The distinctive biological properties of EVs make them a promising natural carrier for oral drug delivery. This review introduces the characteristics of EVs, covering their classification, production methods, and therapeutic efficacy in oral administration. Additionally, we explore the potential roles of EVs in disease prevention and treatment, as well as their future prospects in pharmaceutical applications. This comprehensive overview aims to provide insights into the application of EVs in oral drug delivery, highlighting their advantages, current progress, and the challenges that need to be overcome for successful clinical translation., (© 2025 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Background & Problems: Oral administration is the most common mode of medical treatment for pediatric patients. Although over 98% of the patients in the targeted pediatric unit require oral medication, the oral administration adherence rate in 2022 was 43.9%. The reasons for this low rate were identified as: (1) no relevant oral administration educational materials, (2) no relevant continued nursing education provided, and (3) lack of assistive tools and feeding aids to help administer oral medication to young children., Purpose: This project was developed to increase the adherence rate of oral administration of preschool pediatric inpatients in our hospital., Resolutions: The improvement strategies included the design of patient-centered oral medication care guidance leaflets and QR code (quick response code) video links, the development of therapeutic play aids, adding cartoon characters to medicine feeders, and the creation of a "Rescue the Forest" picture book and video and reward stickers., Results: The oral medication adherence rate increased from 43.9% pretest to 91.9% posttest., Conclusions: This project and its positive effect on the rate of oral medication adherence may be referenced by other pediatric units.

Despite being a groundbreaking approach to treating colorectal cancer (CRC), the efficacy of immunotherapy is significantly compromised by the immunosuppressive tumor microenvironment and dysbiotic intestinal microbiota. Here, leveraging the superior carrying capacity and innate immunity-stimulating property of living bacteria, a nanomedicine-engineered bacterium, LR-S-CD/CpG@LNP, with optical responsiveness, immune-stimulating activity, and the ability to regulate microbiota metabolome is developed. Immunoadjuvant (CpG) and carbon dot (CD) co-loaded plant lipid nanoparticles (CD/CpG@LNPs) are constructed and conjugated to the surface of Limosilactobacillus reuteri (LR) via reactive oxygen species (ROS)-responsive linkers. The inherent photothermal and photodynamic properties of oral CD/CpG@LNPs induce in situ cytotoxic ROS generation and immunogenic cell death of colorectal tumor cells. The generated neoantigens and the released CpG function as a potent in situ vaccine that stimulates the maturation of immature dendritic cells. The mature dendritic cells and metabolites secreted by LR subsequently facilitated the tumor infiltration of cytotoxic T lymphocytes to eradicate colorectal tumors. The further in vivo results demonstrate that the photo-immunotherapy and intestinal microbial metabolite regulation of LR-S-CD/CpG@LNPs collectively suppressed the growth of orthotopic colorectal tumors and their liver metastases, presenting a promising avenue for synergistic treatment of CRC via the oral route., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: The purpose of this study was to evaluate the effects of preoperative oral carbohydrate (CHO) loading on postoperative insulin resistance, hospital stay, and pain in patients undergoing elective arthroplasty., Methods: Clinical randomized controlled trials (RCTs) on the effects of preoperative oral CHO loading in patients undergoing elective hip and knee arthroplasty were searched on PubMed, Web of Science, Cochrane Library, Embase, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure (CNKI) from inception to February 2024. The Cochrane Risk of Bias Assessment Tool was used to evaluate the quality of the enrolled RCTs., Results: There were 16 papers included. Meta-analysis unveiled that compared with the control group, the test group had notably reduced postoperative anxiety scores [SMD (standard mean difference)= -0.06, 95% CI (confidence interval) (-0.42 to 0.30)] and complication rates [OR (odds ratio) = 0.64, 95% CI (0.41 to 0.99)] and enhanced postoperative active GLP-1 levels after preoperative oral CHO loading [SMD = 0.46, 95% CI (0.06 to 0.86)]. There was no marked difference in postoperative blood glucose levels, hospitalization time, insulin levels, and pain score., Conclusions: Available evidence suggests that preoperative oral CHO loading in patients undergoing arthroplasty may reduce related complications, improve postoperative active GLP-1 levels, and alleviate postoperative anxiety., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Portal vein tumor thrombus (PVTT) is a poor prognostic factor for hepatocellular carcinoma (HCC) patients, highlighting the need for an oral drug delivery system that combines convenience, simplicity, biosafety, and improved patient compliance. Leveraging the unique anatomy of the portal vein and insights from single-cell RNA sequencing of the PVTT tumor microenvironment, we developed oral pellets using CaCO 3 @PDA nanoparticles (NPs) encapsulating both doxorubicin hydrochloride and low molecular weight heparin. These NPs target the tumor thrombus microenvironment, aiming to break down the thrombus barrier and turn the challenge of portal vein blockage into an advantage by enhancing drug delivery efficiency through oral administration. The NPs-based oral delivery system achieved excellent antitumor effects with minimal side effects, demonstrating a promising strategy for managing PVTT in advanced HCC and addressing tumor types associated with vascular invasion and hypercoagulability.

Hematopoietic progenitor pinase1 (HPK1) knockout has been identified as an efficient route to enhance anti-tumor immune response. Here, this work develops an oral proteolysis targeting chimera (PROTAC) targeting HPK1 to efficiently and selectively degrade HPK1 to augment immunotherapeutic outcomes. In a postoperative tumor model of human cervical cancer in NSG mice, the orally-administrated PROTAC can reach tumors, down-regulate HPK1 levels in locally-administrated CAR-T cells, and promote their efficiency in inhibiting solid tumor recurrence, achieving 50% partial response (PR) and 50% complete response (CR). In addition, oral administration of PROTAC can amplify the suppression capability of the anti-PD-L1 antibody on the growth of CT26 solid tumors in BALB/c mice by promoting the infiltration of CD45-positive immune cells from 0.7% to 1.5% and CD3-positive T cells from 0.2% to 0.5% within the tumors., (© 2024 Wiley‐VCH GmbH.)

Background/aim: Salmonella typhimurium A1-R (A1-R) targets and inhibits a wide range of cancer types without continuously infecting healthy tissue. Chloroquine, an antimalarial drug, induces apoptosis and inhibits autophagy in cancer cells. The aim of the present study was to determine the synergy of A1-R plus chloroquine on HT1080 human fibrosarcoma cells in vitro and in a nude-mouse model., Materials and Methods: HT1080 human fibrosarcoma cells were used for in vitro experiments. Four groups were analysed in vitro: No-treatment control; A1-R; chloroquine; A1-R plus chloroquine. The nude-mouse models of HT1080 human fibrosarcoma were randomly assigned into four groups: G1: untreated control; G2: Oral A1-R [5×10 7 colony forming units (CFU)/body, twice a week, 2 weeks]; G3: Chloroquine [100 mg/kg/body, intraperitoneal (IP) administration, twice a week, 2 weeks]; G4: Oral A1-R (5×10 7 CFU/body), twice a week, 2 weeks plus chloroquine (100 mg/kg/body, IP), twice a week, 2 weeks. Each cohort consisted of five mice. Tumor volume and body weight were assessed biweekly., Results: A1-R combined with chloroquine synergistically decreased the viability of HT1080 cells in vitro compared to other groups. Orally-administered A1-R at 5×10 7 CFU combined with IP-administered chloroquine eradicated HT1080 tumors in nude mice, without body-weight decrease., Conclusion: The combination treatment of A1-R plus chloroquine demonstrated synergy against HT1080 cancer cells in vitro and in vivo. A1-R was administered orally, suggesting its potential as a probiotic. The present results suggest the clinical potential of the combination of A1-R and chloroquine for soft-tissue sarcoma therapy, a recalcitrant disease., (Copyright © 2025, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)