Physiological Barriers Research Articles

Nanomedicine in the treatment of Alzheimer's disease: bypassing the blood-brain barrier with cutting-edge nanotechnology.

Alzheimer's disease (AD) remains a formidable challenge in the field of neurodegenerative disorders, necessitating innovative therapeutic strategies. Nanomedicine, leveraging nanomaterials, has emerged as a promising avenue for AD treatment, with a key emphasis on overcoming the blood-brain barrier (BBB) to enhance drug delivery efficiency. This review provides a comprehensive analysis of recent advancements in the application of nanomaterials for AD therapy, highlighting their unique properties and functions. The blood-brain barrier, a complex physiological barrier, poses a significant hurdle for traditional drug delivery to the brain. Nanomedicine addresses this challenge by utilizing various nanomaterials such as liposomes, polymeric nanoparticles, and metal nanoparticles. These nanocarriers enable improved drug bioavailability, sustained release, and targeted delivery to specific brain regions affected by AD pathology. The review discusses the diverse range of nanomaterials employed in AD treatment, exploring their capacity to encapsulate therapeutic agents, modulate drug release kinetics, and enhance drug stability. Additionally, the multifunctionality of nanomaterials allows for simultaneous imaging and therapy, facilitating early diagnosis and intervention. Key aspects covered include the interaction of nanomaterials with Aβ aggregates, the role of antioxidants in mitigating oxidative stress, and the potential of nanomedicine in alleviating neuroinflammation associated with AD. Furthermore, the safety, biocompatibility, and toxicity profiles of various nanomaterials are scrutinized to ensure their clinical applicability. In conclusion, this review underscores the pivotal role of nanomedicine and nanomaterials in revolutionizing AD treatment strategies. By specifically addressing BBB challenges, these innovative approaches offer new avenues for targeted drug delivery and improved therapeutic outcomes in the complex landscape of Alzheimer's disease.

Biopolymeric Inhalable Dry Powders for Pulmonary Drug Delivery

Natural and synthetic biopolymers are gaining popularity in the development of inhaled drug formulations. Their highly tunable properties and ability to sustain drug release allow for the incorporation of attributes not achieved in dry powder inhaler formulations composed only of micronized drugs, standard excipients, and/or carriers. There are multiple physiological barriers to the penetration of inhaled drugs to the epithelial surface, such as the periciliary layer mucus mesh, pulmonary macrophages, and inflammation and mucus compositional changes resulting from respiratory diseases. Biopolymers may facilitate transport to the epithelial surface despite such barriers. A variety of categories of biopolymers have been assessed for their potential in inhaled drug formulations throughout the research literature, ranging from natural biopolymers (e.g., chitosan, alginate, hyaluronic acid) to those synthesized in a laboratory setting (e.g., polycaprolactone, poly(lactic-co-glycolic acid)) with varying structures and compositions. To date, no biopolymers have been approved as a commercial dry powder inhaler product. However, advances may be possible in the treatment of respiratory diseases and infections upon further investigation and evaluation. Herein, this review will provide a thorough foundation of reported research utilizing biopolymers in dry powder inhaler formulations. Furthermore, insight and considerations for the future development of dry powder formulations will be proposed.

Bioinspired micro- and nanostructured systems for cancer therapy.

Numerous organisms in nature have demonstrated enhanced biocompatibility, precise tumor targeting capabilities, and efficient tissue traversal within the human body. Drawing inspiration from these organisms, researchers have employed bioengineering, bioconjugation, and micro- or nanotechnology to fabricate bioinspired micro- and nanostructured systems. These systems play a crucial role in addressing the limitations of conventional anticancer drugs and nanomaterials concerning biocompatibility, effective penetration of physiological barriers, as well as selective tumor targeting, thereby leading to improved therapeutic efficacy while minimizing nonspecific adverse effects on healthy cells. Consequently, extensive exploration of these bioinspired micro- and nanostructured systems has been undertaken across various cancer treatment modalities with some progressing into preclinical or clinical stages. However, our understanding of this field remains limited which may impede research progress, clinical translation efforts, and practical applications. Therefore, this study presents a systematic classification of bioinspired micro- and nanostructured systems for cancer therapy that comprehensively elucidates their sources of inspiration and design principles. Furthermore, it extensively discusses the current status of clinical translation efforts while identifying prevailing challenges and exploring future prospects. This work will establish a robust theoretical framework and serve as a valuable reference to facilitate advancements in research and clinical application within this field.

In Situ Photo Responsive Biodegradable Nanoparticle Forming Intrauterine Implant for Drug Delivery to Treat Ovarian Diseases: A Rationale-based Review.

Ovarian disease constitutes various types of endocrine disorders, such as polycystic ovarian syndrome (PCOS), ovarian cancer, premature ovarian failure, ovarian endometriosis, and ovarian cysts. The prevalence of ovarian-related diseases is highly vulnerable in the world. The utility of various drug delivery systems for ovarian diseases has resulted in varied success. Moreover, most of them lead to severe adverse effects and are incapable of ameliorating the signs and symptoms of the condition. Intrauterine devices (IUDs) have positioned themselves as a mechanism to deliver the drug for various ovarian-related diseases. Thereby avoiding various stability-related issues arising due to various physiological barriers of the female reproductive tract. However, the use of intrauterine devices for drug delivery to the ovaries has not been fully explored. This is attributed to the fact that they cause cysts in the ovaries and skepticism among patients and physicians. Photo-sensitive devices are an appealing approach for managing disorders affecting the ovaries. Photo-sensitive in situ forming intrauterine implants (IUIs) have several advantages, including simplicity in application, reduced invasiveness, as well as improved site-specific drug release control. Polymeric nanoparticles (PNPs) loaded with a drug may be a suitable choice to provide sustained release, alter the pharmacokinetics, and reduce the dose and dosing frequency. The current manuscript hypothesizes the utility of a PNP-loaded biodegradable photo-responsive intrauterine implantable device as an alternate novel strategy for ameliorating ovarian-related diseases.

Latest developments in biomaterial interfaces and drug delivery: challenges, innovations, and future outlook.

An ideal drug carrier system should demonstrate optimal payload and release characteristics, thereby ensuring prolonged therapeutic index while minimizing adverse effects. The field of drug delivery has undergone significant advancements, particularly within the last two decades, owing to the revolutionary impact of biomaterials. The use of biomaterials presents significant due to their biocompatibility and biodegradability, which must be addressed in order to achieve effective drug delivery. The properties of the biomaterial and its interface are primarily influenced by their physicochemical attributes, physiological barriers, cellular trafficking, and immunomodulatory effects. By attuning these barriers, regulating the physicochemical properties, and masking the immune system's response, the biointerface can be effectively modulated, leading to the development of innovative supramolecular structures with enhanced effectiveness. With a comprehensive understanding of these technologies, there is a growing demand for repurposing existing drugs for new therapeutic indications within this space. This review aims to provide a substantial body of evidence showcasing the productiveness of biomaterials and their interface in drug delivery, as well as methods for mitigating and modulating barriers and physicochemical properties along with an examination of future prospects in this field.

Nanomotors activating both cGAS-STING pathway and immune checkpoint blockade for tumor therapy and bioimaging

Cellular innate immune response is closely related to cGAS-STING pathway and PD-1/PD-L1 immune checkpoint blockade. The lack of tissue penetration of STING agonists and nanomedicines in conventional approaches reduces their immunotherapeutic efficacy. At the same time, because the cGAS-STING signaling pathway is silent in many breast cancer cells, it cannot play its role. To address these challenges, here, we developed a silica nanomotor based on bubble propulsion. Its hollow structure was packed with the photosensitizer Ce6 molecule. Under 808 nm laser irradiation, Ce6 produced 1O2, which lead to intracellular DNA damage and further activated the cGAS-STING pathway, stimulating the maturation of DC cells, and enhancing the tumor infiltration of CD8+ T cells. The nanomotor had an asymmetrical structure. One side of the nanomotor was modified with Pt nanoparticle. This asymmetric modification can catalyze H2O2 in the environment, producing an asymmetric concentration of O2, which realized the bubble driving nanomotor movement and enhances penetration into breast cancer cells of nanomotor. The other side of the nanomotor was modified the LXL-1 aptamer, triphenylphosphine and peptide CLP002. Peptide CLP002 specifically bound residues of PD-L1 interaction with PD-1, blocked the mutual binding between PD-1 and PD-L1, and further improved the immune response ability of tumor infiltrating T cells. In this study, we developed a multi-pronged immunotherapy strategy of intelligent target finding, breaking through the physiological barrier through kinetic energy, accurately intervening the target and bioimaging, providing a new idea for breast cancer cells targeted therapy.

A Reflective Thematic Analysis Into the Perceptions of Pregnant Radiographers Regarding the Usefulness of the PregiDose Mobile App to Enhance Fetal Dosimetry and Well-Being: Qualitative Exploration.

Pregnancy apps are widely used by pregnant women, who benefit from self-tracking features to support their health goals. Pregnant radiographers are considered a high-risk group of health workers practicing in ionizing radiation environments. Radiation exposure above threshold limits can cause harmful genetic effects on a fetus. Accordingly, pregnant radiographers are required to wear special fetal dosimeters, which provide real-time readings of radiation dose exposure to the fetus. Pregnant radiographers have the responsibility to self-track their fetal doses to ensure that the threshold limit of 1 mGy is not exceeded. The traditional method used to track doses includes a written log of doses in a notebook. Thus, PregiDose, a unique offering in the context of pregnancy apps, was developed to enhance fetal dose tracking and monitoring using technological methods. This study aims to describe the users' perceptions of the app's usefulness using PregiDose in a natural setting. The overarching framework adopted for the study was a design science research (DSR) methodology encompassing five steps, namely (1) problem awareness, (2) suggestion, (3) development, (4) evaluation, and (5) conclusion. This paper presents the evaluation step of DSR. DSR step 4 included a qualitative approach to explore users' perceptions regarding the app. Data were collected using a semistructured interview guide. Open-ended questions were guided by the app's core features, namely dose tracking, education, and wellness. In total, 17 pregnant radiographers in South Africa enrolled to use the app, 9 (53%) engaged with the app, and 4 (24%) agreed to participate in the feedback interviews. The data were collected from October 2023 to March 2024 and analyzed using a reflective thematic data analysis method. Three overarching themes emerged from the data, namely (1) usefulness of PregiDose, (2) barriers to PregiDose adoption and use, and (3) recommendations for the advancement of PregiDose. Users labeled the app's usefulness as positive and perceived it as a modern approach to traditional dose-tracking methods. They perceived the graph output of the dose-tracking feature to be useful for viewing their accumulative doses. They did not fully engage with the journaling feature, indicating that it was a personal preference and not a practice they would usually engage in. Physiological barriers, such as fatigue and "pregnancy brain," were contributors to decreased engagement. Finally, because of the demanding workload and fast-paced nature of the radiography department, users recommended the automation of fetal dosimetry through the Internet of Things. PregiDose is an occupational health and safety mobile app developed for pregnant radiographers through a DSR approach. The app offers a modern method of dose tracking consistent with technological advancements in the context of self-tracking. However, future implementation would require using Internet of Things to make fetal dose tracking more effective.

Modified PEG-Lipids Enhance the Nasal Mucosal Immune Capacity of Lipid Nanoparticle mRNA Vaccines.

Omicron, the predominant variant of SARS-CoV-2, exhibits strong immune-evasive properties, leading to the reduced efficacy of existing vaccines. Consequently, the development of versatile vaccines is imperative. Intranasal mRNA vaccines offer convenient administration and have the potential to enhance mucosal immunity. However, delivering vaccines via the nasal mucosa requires overcoming complex physiological barriers. The aim of this study is to modify PEGylated lipids to enhance the mucosal immune efficacy of the vaccine. The PEGylated lipid component of lipid nanoparticle (LNP) delivery vectors was modified with chitosan or mannose to generate novel LNPs that enhance vaccine adhesion or targeting on mucosal surfaces. The impact of the mRNA encoding the receptor-binding domain of Omicron BA.4/BA.5 on the immune response was examined. Compared to the unmodified LNP group, the IgG and IgA titers in the chitosan or mannose-modified LNP groups showed an increasing trend. The chitosan-modified group showed better effects. Notably, the PEGylated lipid with 1.5 mol% of chitosan modification produced high levels of IgG1 and IgG2a antibodies, promoting Th1/Th2 responses while also generating high levels of IgA, which can induce stronger cellular immunity, humoral immunity, and mucosal immunity. The 1.5 mol% of chitosan-modified LNPs (mRNA-LNP-1.5CS) can serve as a safe and effective carrier for intranasal mRNA vaccines, offering a promising strategy for combating the Omicron variant.

Standalone single- and bi-layered human skin 3D models supported by recombinant silk feature native spatial organization

Physiologically relevant human skin models that include key skin cell types can be used forin vitrodrug testing, skin pathology studies, or clinical applications such as skin grafts. However, there is still no golden standard for such a model. We investigated the potential of a recombinant functionalized spider silk protein, FN-silk, for the construction of a dermal, an epidermal, and a bilayered skin equivalent (BSE). Specifically, two formats of FN-silk (i.e. 3D network and nanomembrane) were evaluated. The 3D network was used as an elastic ECM-like support for the dermis, and the thin, permeable nanomembrane was used as a basement membrane to support the epidermal epithelium. Immunofluorescence microscopy and spatially resolved transcriptomics analysis demonstrated the secretion of key ECM components and the formation of microvascular-like structures. Furthermore, the epidermal layer exhibited clear stratification and the formation of a cornified layer, resulting in a tight physiologic epithelial barrier. Our findings indicate that the presented FN-silk-based skin models can be proposed as physiologically relevant standalone epidermal or dermal models, as well as a combined BSE.

Functional Assessment of a Bioprinted Immuno-Mimetic Peyer's Patch Recapitulating Gut-Associated Lymphoid Tissue.

Gut immune models have attracted much interest in better understanding the microbiome in the human gastrointestinal tract. The gut-associated lymphoid tissue (GALT) has complex structures that interact with microorganisms, including the intestinal monolayer as a physiological barrier and the Peyer's patch (PP) involved in the immune system. Although essential for studying GALT and microbiome interactions, current research often uses simplified models that only recapitulate some components. In this study, GALT is recapitulated to consider the morphology and function of lymphocyte-containing PP beneath the intestinal monolayer and to analyze microbiome interaction. Using the bioprinting technique, a dome-shaped structure array for the PP is fabricated, and epithelial cells are cocultured to form the intestinal monolayer. The developed GALT model shows stable cell differentiation on the hydrogel while exhibiting durability against lipopolysaccharides. It also exhibits increased responsiveness to Escherichia coli, as indicated by elevated nitric oxide levels. In addition, the model underscores the critical role of GALT in maintaining bacterial coexistence and in facilitating immune defense against foreign antigens through the secretion of immunoglobulin A by lymphocyte spheroids. The proposed GALT model is expected to provide significant insights into studying the gut-immune system complexity and microbiome.

Developments in Emerging Topical Drug Delivery Systems for Ocular Disorders.

According to the current information, using nano gels in the eyes have therapeutic benefits. Industry growth in the pharmaceutical and healthcare sectors has been filled by nanotechnology. Traditional ocular preparations have a short retention duration and restricted drug bioavailability because of the eye's architectural and physiological barriers, a big issue for physicians, patients, and chemists. In contrast, nano gels can encapsulate drugs within threedimensional cross-linked polymeric networks. Because of their distinctive structural designs and preparation methods, they can deliver loaded medications in a controlled and sustained manner, enhancing patient compliance and therapeutic efficacy. Due to their excellent drugloading capacity and biocompatibility, nano-gels outperform other nano-carriers. This study focuses on using nano gels to treat eye diseases and provides a brief overview of their creation and response to stimuli. Our understanding of topical drug administration will be advanced using nano gel developments to treat common ocular diseases such as glaucoma, cataracts, dry eye syndrome, bacterial keratitis, and linked medication-loaded contact lenses and natural active ingredients.

Preservative-free electrospun nanofibrous inserts for sustained delivery of ceftazidime; design, characterization and pharmacokinetic investigation in rabbit's eye

Ocular drug delivery presents significant challenges, attributed to the various anatomical and physiological barriers, as well as the limitations associated with conventional ocular formulations including low bioavailability, necessitating frequent dosing. The objective of the essay was to design sustained release nanofibrous inserts loaded with ceftazidime (CAZ), an antibiotic effective against gram-negative and gram-positive microorganisms, for the treatment of ocular infections. These nanofibers were fabricated using the electrospinning technique, employing biodegradable polymers such as polyvinyl alcohol (PVA), polycaprolactone (PCL) and Eudragit® (EUD). The nanofibrous inserts exhibited adequate mechanical strength for ocular use with an average diameter < 250 nm. In the initial 12-h period, a burst drug release was observed, followed by a controlled release for 120 h. Cell viability test confirmed the non-toxicity and safety of the nanofibers. The in vivo study demonstrated that the inserts sustain a drug concentration exceeding the minimum inhibitory concentration (MIC) of Pseudomonas aeruginosa and Staphylococcus aureus for 4 and 5 days, respectively. The AUC0–120 for CAZ-PVA-PCL was reported 11,882.81 ± 80.5 μg·h/ml and for CAZ-PVA-EUD was 9649.39 ± 86.84 μg·h/ml. The nanofibrous inserts' extended drug release maintains effective antimicrobial concentrations, avoids the fluctuations of eye drops, and, by being preservative-free, eliminates cytotoxicity.

Tetrahydropyrimidine Ionizable Lipids for Efficient mRNA Delivery.

Lipid nanoparticles (LNPs) have emerged as an effective and promising technology for messenger RNA (mRNA) delivery, offering a potential solution to physiological barriers and providing an alternative approach to gene therapy without the drawbacks associated with viral delivery. However, efficiently delivering mRNA remains a significant challenge in nucleic acid-based therapies due to the limitations of current LNP platforms in achieving optimal endosomal escape and mRNA release, which largely relies on finding a suitable ionizable lipid. Additionally, the synthesis of these ionizable lipids involves multiple chemical reactions, often making the process time-consuming and difficult to translate. In this study, we employed a facile, catalyst-free, and versatile one-pot multicomponent reaction (MCR) to develop a library of ionizable lipids featuring a pharmacologically significant tetrahydropyrimidine (THP) backbone, tailored for enhanced mRNA delivery. A library of 26 THP ionizable lipids was systematically synthesized in just 3 h and formulated with luciferase mRNA for initial in vitro screening. The THP LNPs exhibited tunable particle sizes, favorable ζ-potentials, and high encapsulation efficiencies. Among them, THP1 demonstrated the highest transfection efficiency both in vitro and in vivo after intramuscular administration, comparable to DLin-MC3-DMA (MC3), a conventional benchmark. Further optimization of THP1 with phospholipids significantly enhanced intramuscular mRNA delivery and showed sustained protein expression in vivo for up to 5 days. More importantly, it demonstrated successful intravenous delivery in a dose-dependent manner with minimal toxicity, as indicated by hematological, histopathological, and proinflammatory cytokine assessments. Furthermore, THP1 LNPs also demonstrated the ability to edit genes in specific liver tissues in a tdTomato transgenic mouse model, highlighting their precision and utility in targeted therapeutic applications. These findings position THP1 LNPs as promising candidates for advancing mRNA-based therapies, with significant implications for clinical translation in vaccine delivery and CRISPR/Cas9-mediated gene editing in the liver.

A Self-Assembled Transdermal Nanomedicines Incorporating Pendant Disulfides for Non-Invasive, Synergistic Treatment of Melanoma.

Transdermal drug delivery system (TDDS) offers lower systemic toxicity and good patient compliance, making it a promising treatment option for skin-related cancers. However, physiological barriers in the skin frequently impede the therapeutic efficiency of TDDS. To address this, a unique self-assembled TDDS that incorporates disulfide pendant groups (termed Sup-TDDS) is presented. It is formulated with dithiolane-containing lipoic acid (LA), photosensitizers Ce6, and chemotherapeutic agents trametinib. Pendant disulfide moieties on Sup-TDDS facilitate thiol-disulfide exchange reactions with exofacial thiols on cell surfaces, thus enhancing stratum corneum penetration. In contrast to intravenous injection, topical administration of Sup-TDDS can penetrate deeper into the skin (> 500 µm) and promote drug accumulation in subcutaneous tumors. In a B16F10-bearing mouse model, Sup-TDDS treatment demonstrates significant anti-tumor effects in primary and recurrent melanoma, benefiting from the synergistic effects of Ce6 and trametinib. These results underscore that Sup-TDDS's transdermal properties allow non-invasive melanoma therapy, implying the potential of nanodrugs containing pendant disulfides for transdermal treatment of skin illnesses.

Therapeutic Contact Lenses for Intraocular Drug Administration: Innovations and Applications in Treating Fungal Keratitis

This review examines the advancements in ocular medication administration, focusing on therapeutic contact lenses (TCLs) as a novel approach for treating fungal keratitis. Traditional eye Drops' bioavailability is poor due to various anatomical and physiological barriers, necessitating frequent administration and leading to poor patient compliance. TCLs offer a promising alternative, providing extended drug release, improved bioavailability, and enhanced patient comfort. This review explores different antifungal drugs, innovative methods for drug incorporation into TCLs, and their therapeutic efficacy. The potential of TCLs to revolutionize ocular drug delivery and improve treatment outcomes for fungal keratitis is discussed.

Advancements in Ocular Therapy: A Review of Emerging Drug Delivery Approaches and Pharmaceutical Technologies

Eye disorders affect a substantial portion of the global population, yet the availability of efficacious ophthalmic drug products remains limited. This can be partly ascribed to a number of factors: (1) inadequate understanding of physiological barriers, treatment strategies, drug and polymer properties, and delivery systems; (2) challenges in effectively delivering drugs to the anterior and posterior segments of the eye due to anatomical and physiological constraints; and (3) manufacturing and regulatory hurdles in ocular drug product development. The present review discusses innovative ocular delivery and treatments, encompassing implants, liposomes, nanoparticles, nanomicelles, microparticles, iontophoresis, in situ gels, contact lenses, microneedles, hydrogels, bispecific antibodies, and gene delivery strategies. Furthermore, this review also introduces advanced manufacturing technologies such as 3D printing and hot-melt extrusion (HME), aimed at improving bioavailability, reducing therapeutic dosages and side effects, facilitating the design of personalized ophthalmic dosage forms, as well as enhancing patient compliance. This comprehensive review lastly offers insights into digital healthcare, market trends, and industry and regulatory perspectives pertaining to ocular product development.

Delivery Aspects for Implementing siRNA Therapeutics for Blood Diseases.

Hematological disorders result in significant health consequences, and traditional therapies frequently entail adverse reactions without addressing the root cause. A potential solution for hematological disorders characterized by gain-of-function mutations lies in the emergence of small interfering RNA (siRNA) molecules as a therapeutic option. siRNAs are a class of RNA molecules composed of double-stranded RNAs that can degrade specific mRNAs, thereby inhibiting the synthesis of underlying disease proteins. Therapeutic interventions utilizing siRNA can be tailored to selectively target genes implicated in diverse hematological disorders, including sickle cell anemia, β-thalassemia, and malignancies such as lymphoma, myeloma, and leukemia. The development of efficient siRNA silencers necessitates meticulous contemplation of variables such as the RNA backbone, stability, and specificity. Transportation of siRNA to specific cells poses a significant hurdle, prompting investigations of diverse delivery approaches, including chemically modified forms of siRNA and nanoparticle formulations with various biocompatible carriers. This review delves into the crucial role of siRNA technology in targeting and treating hematological malignancies and disorders. It sheds light on the latest research, development, and clinical trials, detailing how various pharmaceutical approaches leverage siRNA against blood disorders, mainly concentrating on cancers. It outlines the preferred molecular targets and physiological barriers to delivery while emphasizing the growing potential of various therapeutic delivery methods. The need for further research is articulated in the context of overcoming the shortcomings of siRNA in order to enrich discussions around siRNA's role in managing blood disorders and aiding the scientific community in advancing more targeted and effective treatments.

Hydroxamate Siderophores Intensify the Co-Deposition of Cadmium and Silicon as Phytolith-Like Particulates in Rice Stem Nodes: A Natural Strategy to Mitigate Grain Cadmium Accumulation.

Sequestration of cadmium (Cd) in rice phytolith can effectively restrict its migration to the grains, but how hydroxamate siderophore (HDS) affects phytolith formation within rice plants especially the fate of Cd and silicon (Si) remains poorly understood. Here, we found that the addition of HDS increased the content of dissolved Si and Cd in soil pore water as well as its absorption by the rice roots during the reproductive growth stage. HDS effectively trapped orthosilicic acid and Cd ions at the third stem nodes of rice plants via hydrogen bonds and chelation interactions, which then rapidly deposited on the xylem cell wall through hydrophobic interactions. Ultimately, Cd was immobilized as phytolith-like particulates in the form of CdSiO3. Field experiments verified that Cd accumulation was significantly reduced by 46.4% in rice grains but increased by 41.2% in rice stems after HDS addition. Overall, this study advances our understanding of microbial metabolites enhancing the instinctive physiological barriers within rice plants.

Dynamic Liver Chip Based on Well-Coupled Microfluidics: An Accurate NASH Model for Drug Evaluation.

The convenient liver model in vitro recapitulating the hepatic functions, metabolism, and even steatohepatitis to perform the accurate drug evaluation is still challenging because of the unattainable hominine physiological microenvironment in vitro. Here, the progressed stages of nonalcoholic steatohepatitis (NASH) disease were precisely modeled to accurately evaluate the performance of antilipemic based on the dynamic liver chip adopting the well-coupled microfluidics, which well recapitulated the normal and steatohepatitis of liver in vitro. In brief, the mild nutrient flow and sufficient oxygen supply for parenchymal liver cells could be well supplied through the endothelial cells layer that mimicked the real physiological barrier of endothelium, while the loading of drugs might be obtained by directly adding drug into the running nutrient flow to mimic the intravenously administrable. The progressed degree of steatohepatitis could be directly reflected by the amount of intramyocellular lipid content (IMLC) of the HepG2 cell hepatocyte layer in wells that were induced by different concentrations of free fatty acids (FFA). To prove the concept of the liver chip in drug evaluation, an accurate assessment of the performance of firsocostat, the acetyl-CoA carboxylase (ACC) inhibitor of hepatic mitochondria of hepatocytes, was carried out. The subtle time dependence of firsocostat treatment to different progressed stages of NASH was clearly figured out. Therefore, we prospect the liver chip that adopted well-coupled microfluidics could be an accurate and standard liver model in vitro to carry out the antilipemic evaluation and screening, which significantly enlightens the drug evaluation by liver on chip in vitro.

"Enhancing Oral Drug Absorption: Overcoming Physiological and Pharmaceutical Barriers for Improved Bioavailability".

The oral route stands out as the most commonly used method for drug administration, prized for its non-invasive nature, patient compliance, and easy administration. Several elements influence the absorption of oral medications, including their solubility, permeability across mucosal membranes, and stability within the gastrointestinal (GI) environment. Research has delved into comprehending physicochemical, biochemical, metabolic, and biological obstacles that impact the bioavailability of a drug. To improve oral drug absorption, several pharmaceutical technologies and delivery methods have been studied, including cyclodextrins, micelles, nanocarriers, and lipid-based carriers. This review examines both traditional and innovative drug delivery methods, as well as the physiological and pharmacological barriers influencing medication bioavailability when taken orally. Additionally, it describes the challenges and advancements in developing formulations suitable for oral use.