Drug Delivery Research Articles

Elucidating the E‐Cadherin⋯ADTC5 Interactions: A Theoretical Examination of Amino Acid Active Site Binding on the Electronic Level via Density Functional Theory

AbstractThe presence of E‐cadherin⋯E‐cadherin interactions in the intercellular space (paracellular pathway) poses a notable limitation in drug delivery across the blood‐brain barrier (BBB). ADTC5 peptide has shown promising results in improving drug delivery across the BBB by modulating E‐cadherin⋯E‐cadherin interactions. However, the study of E‐cadherin⋯ADTC5 amino acid interactions using quantum mechanics approach has not been observed clearly. Herein, we observed the interaction between E‐cadherin⋯ADTC5 amino acids using density functional theory (DFT). Natural bond orbital (NBO), quantum theory of atoms in molecules (QTAIM), and reduced density gradient (RDG) analysis are performed to study the non‐covalent interaction in detail. The Arg55⋯Asp2 shows the strongest interaction between E‐cadherin⋯ADTC5 modulation, indicated by the highest stabilization energy (E(2)), and hydrogen bonding energy (EHB) about 22.04 and −6.90 kcal/mol, respectively. This interaction is dominated by hydrogen bonding. Such advancements could lead to significant improvements in therapeutic strategies for neurodegenerative diseases, where effective drug delivery across the BBB remains a major challenge.

Nanosuspension: A Novel Drug Delivery System

It is over past two years ago. It has technology has been developed R& D pharmaceutical business. Nanotechnology is science is deals with the process that occurs at Molecular level and Nanolength scale size, Nano refer to the particle size range is 1- 1000 micrometre. Nano suspension can be used in oral, topical parenteral and pulmonary route of administration of drug delivery, Nano suspension is used in incorporated into ocular inserts and mucoadhesive hydrocele for targeted drug delivery. There are medication candidate is with very high effectiveness. Nanosuspension was prepared by using combination of high speed homogenization (HSH) and media milling (MM),Poligomer( stabilizer)ZIO2 heads ( milling media). Reducing particle size in Nanosuspension is the primary cause of an increase in .Because of their specific qualities, nanosuspension can be used in a variety of dosage forms, including ones that require specialised delivery methods like mucoadhesive hydrogels.The Atomization of the drug discovery process through technologies like computer-aid drug design, combinatorial chemistry, an high-throughput screening is producing a large number of very effective therapeutic candidates. Regrettably, a lot of these potentiate medications are not very soluble in water. This review article describes the physicochemical properties of drug Nanosuspension, preparation methods and; it’s potential clinical advantages.

In Silico Design of Novel EpCAM-Binding Aptamers for Targeted Delivery of RNA Therapeutics

Aptamers are short DNA or RNA sequences that adopt 3D structures and can bind to protein targets with high binding affinity and specificity. Aptamers exhibit excellent tissue penetration, are inexpensive to produce, and can be internalized by cells. Therefore, aptamers are attractive targeting ligands to direct the delivery of theranostic agents to the desired cells. Epithelial cell adhesion molecule (EpCAM) is a tumor-associated antigen that is aberrantly overexpressed on many epithelial-derived cancers, including on cholangiocarcinoma (CCA) cells. Its expression on treatment-resistant cancer stem cells, along with its abundance in the CCA tumor microenvironment, highlights the need to develop EpCAM-targeted therapies for CCA. Herein, an in silico approach was used to design and screen DNA aptamers capable of binding to the EpCAM monomer and homodimer. Two aptamers, PLD01 and PLD02, met the selection criteria and were validated in vitro. Both aptamers exhibited high affinity for EpCAM+ CCA cells, with negligible binding to EpCAM- leukemia cells. Modified versions of PLD01 and PLD02 were successfully incorporated into the membranes of milk-derived nanovesicles. PLD01-functionalized nanovesicles enabled EpCAM-targeted delivery of the therapeutic cargo to CCA cells. In summary, these EpCAM-targeting aptamers can be utilized to direct the delivery of theranostic agents to EpCAM-expressing cells.

Advances in Chitosan Derivatives: Preparation, Properties and Applications in Pharmacy and Medicine

Chitosan (CS) derivatives have been extensively investigated to enhance the physicochemical and biological properties of CS, such as its solubility, biocompatibility, and bioactivity, which are required in various areas of pharmacy and medicine. The present work emphasizes the ongoing research and development in this field, suggesting that the further exploration of CS derivatives could lead to innovative solutions that benefit society. The physicochemical properties, biological activities, methods of preparation, advantages, limitations, intended application areas, and realized practical implementations of particular CS derivatives are summarized and discussed herein. Despite the numerous promising attributes of CS derivatives as reported in this paper, however, challenges like target selectivity, standardization (purity, chitosan structural variability), and cost-effectiveness still need addressing for widespread implementation, especially in drug delivery. Therefore, basic research studies still prevail in CS drug delivery systems. However, for specific applications such as wound healing and tissue engineering, implementations of CS derivatives in practice are found to be more frequent. To obtain a more complex view of the topic, information from the scientific papers reviewed is supplemented with information from actual patents and clinical studies. Both basic research advances and the most successful and important medical implementations of CS derivatives are discussed concerning further challenges and future perspectives.

Investigation of structural frustration in symmetric diblock copolymers confined in polar discs through cell dynamic simulation

Nanotechnology has opened new avenues for advanced research in various fields of soft materials. Materials scientists, chemists, physicists, and computational mathematicians have begun to take a keen interest in soft materials due to their potential applications in nanopatterning, membrane separation, drug delivery, nanolithography, advanced storage media, and nanorobotics. The unique properties of soft materials, particularly self-assembly, have made them useful in fields ranging from nanotechnology to biomedicine. The discovery of new morphologies in the diblock copolymer system in curved geometries is a challenging problem for mathematicians and theoretical scientists. Structural frustration under the effects of confinement in the system helps predict new structures. This mathematical study evaluates the effects of confinement and curvature on symmetric diblock copolymer melt using a cell dynamic simulation model. New patterns in lamella morphologies are predicted. The Laplacian involved in the cell dynamic simulation model is approximated by generating a 17-point stencil discretized to a polar grid by the finite difference method. Codes are programmed in FORTRAN to run the simulation, and IBM open DX is used to visualize the results. Comparison of computational results with existing studies validates this study and identifies defects and new patterns.

Cell-microsphere based Living Microhybrids for Osteogenesis Regulating to Boosting Biomineralization

Abstract Biomineralization-based cell-material living composites ex vivo showed great potential for living materials construction and cell regulation. However, cells in scaffolds with unconnected pores usually induce confined nutrient transfer and cell-cell communications, affecting the transformation of osteoblasts into osteocytes and the mineralization process. Herein, the osteoblast-materials living hybrids were constructed with porous PLLA microspheres using a rational design, in which cell-based living materials presented an improved osteoblast differentiation and mineralization model using rationally designed cell-microsphere composites. The results indicated that the microfluidic-based technique provided an efficient and highly controllable approach for producing on-demand PLLA microspheres with tiny pores (< 5 μm), medium pores (5-15 μm), and large pores (> 15 μm), as well as further drug delivery. Furthermore, the simvastatin (SIM)-loaded porous PLLA microsphere with ε-polylysine (ε-PL) modification was used for osteoblast (MC3T3-E1) implantation, achieving the cell-material living microhybrids, and the results demonstrated the ε-PL surface modification and simvastatin could improve osteoblast behavior regulation, including cell adhesion, proliferation, as well as the antibacterial effects. Both in vitro and in vivo results significantly demonstrated further cell proliferation, differentiation, and cascade mineralization regulation. Then, the qPCR or histological staining of typical markers, including collagen type I (Col I), alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2) and bone morphogenetic protein 2 (BMP2), as well as the calcium mineral deposition staining in situ, reconfirmed the transformation of osteoblasts into osteocytes. These achievements revealed a promising boost in osteogenesis towards mineralization at the microtissue level by cell-microsphere integration, suggesting an alternative strategy for materials-based ex vivo tissue construction and cell regulation, further demonstrating excellent application prospects in the field of biomineralization-based tissue regeneration.

Microneedles as an Emerging Platform for Transdermal Delivery of Phytochemicals.

Phytochemicals, which are predominantly found in plants, hold substantial medicinal value. Despite their potential, challenges such as poor oral bioavailability and instability in the gastrointestinal tract have limited their therapeutic use. Traditional intra/transdermal drug delivery systems offer some advantages over oral administration but still suffer from issues such as limited penetration depth, slow drug release rates, and inconsistent drug absorption. In contrast, microneedles (MNs) represent a significant advancement in intra/transdermal drug delivery by providing precise control over phytochemical delivery and enhanced penetration capabilities. By circumventing skin barriers, MNs directly access dermal layers rich in blood vessels and lymphatics, thus facilitating efficient phytochemical delivery. This review extensively discusses the obstacles of traditional oral delivery and the benefits of intra/transdermal delivery routes with a particular focus on the transformative potential of MNs for phytochemical delivery. This review explores the complexities of delivering phytochemicals through intra/transdermal routes, the development and types of MNs as innovative delivery tools, and the optimal design and properties of MNs for effective phytochemical delivery. Additionally, this review examines the versatile applications of MN-mediated phytochemical delivery, including its role in administering phytophotosensitizers for photodynamic therapy, and concludes with insights into relevant patents and future perspectives.

Glycocalyx Interactions Modulate the Cellular Uptake of Albumin-Coated Nanoparticles.

Albumin-based nanoparticles (ABNPs) represent promising drug carriers in nanomedicine due to their versatility and biocompatibility, but optimizing their effectiveness in drug delivery requires understanding their interactions with and uptake by cells. Notably, albumin interacts with the cellular glycocalyx, a phenomenon particularly studied in endothelial cells. This observation suggests that the glycocalyx could modulate ABNP uptake and therapeutic efficacy, although this possibility remains unrecognized. In this study, we elucidate the critical role of the glycocalyx in the cellular uptake of a model ABNP system consisting of silica nanoparticles (NPs) coated with native, cationic, and anionic albumin variants (BSA, BSA+, and BSA-). Using various methodologies-including fluorescence anisotropy, dynamic light scattering, microscale thermophoresis, surface plasmon resonance spectroscopy, and computer simulations─we found that both BSA and BSA+, but not BSA-, interact with heparin, a model glycosaminoglycan (GAG). To explore the influence of albumin-GAG interactions on NP uptake, we performed comparative uptake studies in wild-type and GAG-mutated Chinese hamster ovary cells (CHO), along with complementary approaches such as enzymatic GAG cleavage in wild-type cells, chemical inhibition, and competition assays with exogenous heparin. We found that the glycocalyx enhances the cell uptake of NPs coated with BSA and BSA+, while serving as a barrier to the uptake of NPs coated with BSA-. Furthermore, we showed that harnessing albumin-GAG interactions increases cancer cell death induced by paclitaxel-loaded albumin-coated NPs. These findings underscore the importance of albumin-glycocalyx interactions in the rational design and optimization of albumin-based drug delivery systems.

Targeting the undruggable in glioblastoma using nano-based intracellular drug delivery.

Glioblastoma (GBM) is a highly prevalent and aggressive brain tumor in adults with limited treatment response, leading to a 5-year survival rate of less than 5%. Standard therapies, including surgery, radiation, and chemotherapy, often fall short due to the tumor's location, hypoxic conditions, and the challenge of complete removal. Moreover, brain metastases from cancers such as breast and melanoma carry similarly poor prognoses. Recent advancements in nanomedicine offer promising solutions for targeted GBM therapies, with nanoparticles (NPs) capable of delivering chemotherapy drugs or radiation sensitizers across the blood-brain barrier (BBB) to specific tumor sites. Leveraging the enhanced permeability and retention effect, NPs can preferentially accumulate in tumor tissues, where compromised BBB regions enhance delivery efficiency. By modifying NP characteristics such as size, shape, and surface charge, researchers have improved circulation times and cellular uptake, enhancing therapeutic efficacy. Recent studies show that combining photothermal therapy with magnetic hyperthermia using AuNPs and magnetic NPs induces ROS-dependent apoptosis and immunogenic cell death providing dual-targeted, immune-activating approaches. This review discusses the latest NP-based drug delivery strategies, including gene therapy, receptor-mediated transport, and multi-modal approaches like photothermal-magnetic hyperthermia combinations, all aimed at optimizing therapeutic outcomes for GBM.

Integrating AI with Chemical Engineering for Rapid Biomaterial Development in Health Applications

This research presents an innovative approach to healthcare biomaterial development by integrating AI with chemical engineering methodologies. This study combines AI’s predictive power with the precision of chemical engineering to accelerate the discovery and optimization of biomaterials tailored for health applications while focusing on biocompatibility, adaptability, and stringent biomedical functionality. By using machine learning frameworks and advanced simulation software, the project developed predictive models that streamline biomaterial synthesis. This reduced experimental cycles by up to 40% and shortened development timelines by over 30%. Through neural networks and hybrid AI models, material properties such as degradation rate, strength, and biocompatibility can be accurately predicted, which minimizes in vivo testing and accelerates the transition from laboratory research to clinical trials. Protocols optimized through AI-driven insights enhance biomaterial production’s reproducibility and scalability while reducing material costs by 20%, which supports economically viable synthesis methods for large-scale applications. This research contributes a customizable AI framework for health-focused biomaterial solutions and impacts areas such as regenerative medicine, drug delivery, and implantable devices. Future directions include integrating real-time clinical feedback into AI models to improve safety and adaptability, thus advancing sustainable and personalized approaches to biomaterial development. This interdisciplinary framework demonstrates how AI-enhanced chemical engineering workflows can yield adaptive biomaterials suited to specific biomedical needs and offers unprecedented precision in material selection. The model’s high predictive accuracy in biocompatibility screening, achieving over 90%, enables focused experimental validation while reducing the need to rely on animal studies, which fosters ethical research practices. The sustainability impact of this project is significant, as AI-driven optimization reduces resource consumption and waste and aligns with eco-friendly biomaterial development practices. Ultimately, this research paves the way for rapid, efficient, and sustainable innovations in healthcare materials and sets a foundation for future advancements in personalized medical applications.

Reimagining Anti-Inflammatory Drugs Delivery: The Integration of Ordered Mesoporous Silica and MOF Materials for Enhanced Therapeutic Outcomes

Abstract Migraine, one of the neurological conditions, affects approximately 15% of the global population. It is characterized by intense headaches accompanied by nausea, vomiting, and heightened sensitivity to light. The first line of drugs for treating migraine are non-steroidal anti-inflammatory drugs. Unfortunately, these medications suffer from poor solubility in water, uncontrolled release, and numerous adverse side effects. In order to maximize their therapeutic effect by preventing premature release and degradation, novel drug delivery systems based on composites are being dynamically developed. Herein, the biocompatible ketoprofen, naproxen sodium, and diclofenac sodium vehicles integrating ordered mesoporous silica (SBA-16) with Fe-based metal–organic frameworks (MIL-101(Fe)) were synthesized via the solvothermal method. The composites were characterized by different percentages of MIL-101(Fe) 
(25 and 50 wt.%), which had a significant impact on their porosity, structure, and number of functional groups. The SBA-16@MIL-101(Fe)-25 and SBA-16@MIL-101(Fe)-50 samples exhibited BET surface areas of 768 and 324 m2/g, respectively. Their sorption capacities towards selected anti-inflammatory drugs were in the range of 141-318 mg/g for ketoprofen, 481-490 mg/g for naproxen sodium, and 246-589 mg/g for diclofenac sodium, notably exceeding the values obtained for pure mesoporous silica (5-9 mg/g). Morphological defects and specific functional groups, derived from SBA-16 and MIL-101(Fe), contributed to generating new adsorption sites in composites, enhancing host-guest interactions. The drug release profiles were determined by the carrier porosity, surface charge, and the presence of functional groups. The diffusion of ketoprofen and diclofenac sodium from the composites into the phosphate buffer (pH 7.7), mimicking rectal fluid, occurred in a more controlled manner compared to pristine silica. The SBA-16@MIL-101(Fe)-50 carrier released 82% of ketoprofen and 90% of diclofenac sodium over 24 hours.

Transforming Lung Cancer Care: The Role of Transferosomes in Modern Drug Delivery.

Cancer stands as one of the leading causes of death worldwide, and lung cancer represents its most aggressive and persistent form. Traditional strategies for addressing lung cancer involve various medical therapies such as radiotherapy, chemotherapy, and surgical excision. Despite their prevalence, these conventional methods lack precision and inadvert-ently cause collateral damage to neighboring healthy cells. Recently, nanotechnology has emerged as a potential strategy for the treatment and management of lung carcinomas, bring-ing about a transformative shift in existing approaches. The primary focus of this shift is on minimizing harmful effects and improving the bioavailability of chemotherapy drugs specif-ically targeted at tumour cells. Currently, transferosome nanocarrier systems are widely em-ployed to overcome the obstacles presented by lung cancer. The utilization of transferosome-loaded therapeutic medication administration technology holds tremendous potential in reg-ulating tumour cell growth and treating lung cancer. The purpose of this study is to provide an overview and analysis of current advancements in transferosome-based drug delivery sys-tems, employing inhalational nanoparticle strategies for precise drug targeting in lung cancer management.

Enhanced Ocular Drug Delivery of Dexamethasone Using a Chitosan-Coated Soluplus®-Based Mixed Micellar System

Background: This study introduces a novel dexamethasone (DEX) mixed micellar system (DEX-MM) using Soluplus® and Pluronic F-127 (PF127) to enhance ocular drug delivery. The enhancement of ocular application properties was achieved by creating a chitosan-coated DEX-MM (DEX-CMM), which promotes better adherence to the ocular surface, thereby improving drug absorption. Methods: Using the solvent evaporation method, a formulation was developed with a Soluplus®-to-drug ratio of 1:10, enhanced with 0.25% PF127. After dispersing in water, 1% chitosan (CS) was added. The stability and integrity of DEX within the micelles were verified using attenuated total reflection–Fourier transform infrared spectroscopy (ATR-FTIR) and differential scanning calorimetry (DSC). Additionally, in vitro and ex vivo drug release studies were conducted. Results: DEX-CMM (F6) demonstrated a particle size of 151.9 ± 1 nm and a polydispersity index (PDI) of 0.168 ± 0.003, suggesting uniformity and high electrostatic stability with a zeta potential of +35.96 ± 2.13 mV. The non-Fickian drug release mechanism indicated prolonged drug retention. Comparative analyses showed DEX-CMM outperforming a standard DEX suspension in drug release and ocular tissue permeation, with flux measurements significantly higher than the DEX suspension. Conclusion: The study confirmed the efficacy of DEX-CMM in enhancing drug delivery to ocular tissues, evidenced by improved permeability. Safety evaluations using the HET-CAM test demonstrated that DEX-CMM was non-irritant, supporting its potential for effective ocular drug delivery.

Sericin Protein: Structure, Properties, and Applications

Silk sericin, the glue protein binding fibroin fibers together, is present in the Bombyx mori silkworms’ cocoons. In recent years, sericin has gained attention for its wide range of properties and possible opportunities for various applications, as evidenced by the meta-analysis conducted in this review. Sericin extraction methods have evolved over the years to become more efficient and environmentally friendly, preserving its structure. Due to its biocompatibility, biodegradability, anti-inflammatory, antibacterial, antioxidant, UV-protective, anti-tyrosinase, anti-aging, and anti-cancer properties, sericin is increasingly used in biomedical fields like drug delivery, tissue engineering, and serum-free cell culture media. Beyond healthcare, sericin shows promise in industries such as textiles, cosmetics, and food packaging. This review aims to highlight recent advancements in sericin extraction, research, and applications, while also summarizing key findings from earlier studies.

Targeted isolation of extracellular vesicles from cell culture supernatant using immuno-affinity chromatography

Extracellular vesicles (EVs) have emerged as promising therapeutics with broad clinical applications as diagnostic biomarkers and therapeutic drug delivery systems. Yet, these biopharmaceuticals pose a challenge in terms of manufacturing due to their complexity and heterogeneity. Despite advancements in the field, current purification technologies lack scalability and/or selectivity. Affinity chromatography (AC) − coupling unmatched specificity and scalability − could be used to simplify purification processing and generate clinical-grade EVs with higher titers and purity.In the present work, we report the implementation of an immuno-AC resin to capture and purify EVs directly from clarified cellular feedstocks. Firstly, to guide and support marker selection, vesicle phenotype characterization was conducted using single particle interferometric reflectance image sensing (SP-IRIS) coupled with immunofluorescence. CD81 was the marker which shown to be more present and more likely to have the other markers (CD63 and CD9). Thus, anti-CD81 VHH ligand was generated and evaluated towards recombinant CD81 protein and CD81 bearing EV particles using surface plasmon resonance (SPR). Different chromatographic studies with Anti-CD81 ligand immobilized onto agarose beads resin were conducted to optimize the process parameters (residence time, dynamic binding capacity and impurity clearance). At residence time of 2 min, on average 40 % of pure triple tetraspanin-positive EV fraction was recovered. The enrichment in EV particles herein obtained, based on scale-up calculations, it would be possible to produce 1 × 1013 EVs from a 1L cell culture, while meeting impurity requirements in a single-step purification process (impurity removal over 2 log reduction value). A single-step purification process is possible, enabling the successful isolation of homogeneous EVs population, counting with a final HCP titer of 60 ng/mL and 9 ng/mL of dsDNA impurities. EV’s morphological integrity and internalization ability were also demonstrated, showcasing elution’s efficiency under mild conditions.Overall, this work contributes to the development of a novel, highly specific, AC technology using a camelid-derived affinity ligand which, bridging the scalability requirements demanded of large-scale production, could potentiate the advent of EV-based therapies.

Application of Smart Polymer Materialsarts

With the wide application of polymer materials, the performance of ordinary polymer materials gradually cannot meet the shortcomings of use in special environments, such as limited strength, insufficient wear resistance, poor stability and so on. And can not adjust and repair according to changes in the environment. Therefore, the demand for intelligent polymer materials has gradually expanded, and has been applied to a variety of fields after research. This paper introduces the information and application of three kinds of intelligent polymer materials: targeting, shape memory and self-healing. Targeting is mainly used in cancer or other diseases that require precise drug delivery; The characteristics of shape memory can be applied to plaster and surgical sutures in the medical field, and can also be applied to the performance upgrade of traditional manufacturing industry. Self-healing can be used to improve the service life of composite materials by using different methods according to the requirements of different material use scenarios.

Recent Advances of PDMS In Vitro Biomodels for Flow Visualizations and Measurements: From Macro to Nanoscale Applications

Polydimethylsiloxane (PDMS) has become a popular material in microfluidic and macroscale in vitro models due to its elastomeric properties and versatility. PDMS-based biomodels are widely used in blood flow studies, offering a platform for improving flow models and validating numerical simulations. This review highlights recent advances in bioflow studies conducted using both PDMS microfluidic devices and macroscale biomodels, particularly in replicating physiological environments. PDMS microchannels are used in studies of blood cell deformation under confined conditions, demonstrating the potential to distinguish between healthy and diseased cells. PDMS also plays a critical role in fabricating arterial models from real medical images, including pathological conditions such as aneurysms. Cutting-edge applications, such as nanofluid hemodynamic studies and nanoparticle drug delivery in organ-on-a-chip platforms, represent the latest developments in PDMS research. In addition to these applications, this review critically discusses PDMS properties, fabrication methods, and its expanding role in micro- and nanoscale flow studies.

Nanomedicine in Cancer Treatment: Mechanisms, Applications, and Future Directions

Nanomedicine, an emerging field at the intersection of nanotechnology and medicine, holds significant promise for revolutionizing cancer treatment. By utilizing materials at the nanoscale, ranging from 1 to 100 nanometers, nanomedicine offers a versatile platform for targeting tumors, improving drug delivery, and minimizing side effects. This paper explores the design and preparation of nanoparticles, including common materials like liposomes, polymers, metals, and quantum dots, as well as their mechanisms of targeted delivery through both passive and active methods. Key applications of nanomedicine are discussed, particularly in chemotherapy, immunotherapy, and imaging. Clinical progress is highlighted through examples such as FDA-approved drugs like Onivyde for pancreatic cancer and experimental treatments like BIND-014 for metastatic prostate cancer. Despite rapid advancements, significant challenges remain, particularly in scaling up production and ensuring batch consistency. Safety concerns, such as nanoparticle toxicity and unintended accumulation in organs, must be addressed through rigorous testing and design improvements. Ethical considerations and regulatory hurdles also pose obstacles to the widespread clinical adoption of nanomedicine. Looking forward, multifunctionalization and personalized nanomedicine represent key areas of future growth, offering the potential for highly individualized treatments that combine therapeutic and diagnostic capabilities. Continued research and collaboration across scientific disciplines will be crucial in overcoming current limitations and unlocking the full potential of nanomedicine for cancer treatment.

Application of Polymers as Drug Nanocarriers in the Oral Treatment of Ulcerative Colitis

AbstractUlcerative colitis (UC) is a chronic non‐specific inflammatory disease of the intestines with a high prevalence. Polymer‐prepared nanoparticles are well‐targeted, highly biocompatible, and have high potential for personalized therapy. Polymer nanoparticles are able to achieve localized therapy through their unique design. First, this review compares the advantages and disadvantages of natural and synthetic polymeric materials as well as describes the application of polymeric nanoparticles in UC therapy. Then, the preparation, characterization methods, and current challenges of common polymer nanoparticles are presented. Next, one‐by‐one examples of polymer nanoparticle‐targeted drug delivery strategies for the treatment of UC are presented. In addition, polymer nanoparticle‐based therapeutic approaches for UC, including anti‐inflammatory therapies, reactive oxygen species scavenging therapies, and intestinal flora modulation therapies, are presented. Finally, future research directions for polymer nanoparticles in UC therapy are discussed and current challenges are identified. The aim of this paper is to provide valuable references and guidance for researchers to design and develop novel UC therapies.

Region-independent active CNS net uptake of marketed H+/OC antiporter system substrates

The pyrilamine-sensitive proton-coupled organic cation (H+/OC) antiporter system facilitates the active net uptake of several marketed organic cationic drugs across the blood-brain barrier (BBB). This rare phenomenon has garnered interest in the H+/OC antiporter system as a potential target for CNS drug delivery. However, analysis of pharmacovigilance data has uncovered a significant association between substrates of the H+/OC antiporter and neurotoxicity, particularly drug-induced seizures (DIS) and mood- and cognitive-related adverse events (MCAEs). This preclinical study aimed to elucidate the CNS regional disposition of H+/OC antiporter substrates at therapeutically relevant plasma concentrations to uncover potential pharmacokinetic mechanisms underlying DIS and MCAEs. Here, we investigated the neuropharmacokinetics of pyrilamine, diphenhydramine, bupropion, tramadol, oxycodone, and memantine. Using the Combinatory Mapping Approach for Regions of Interest (CMA-ROI), we characterized the transport of unbound drugs across the BBB in specific CNS regions, as well as the blood-spinal cord barrier (BSCB) and the blood-cerebrospinal fluid barrier (BCSFB). Our findings demonstrated active net uptake across the BBB and BSCB, with unbound ROI-to-plasma concentration ratio, Kp,uu,ROI, values consistently exceeding unity in all assessed regions. Despite minor regional differences, no significant distinctions were found when comparing the whole brain to investigated regions of interest, indicating region-independent active transport. Furthermore, we observed intracellular accumulation via lysosomal trapping for all studied drugs. These results provide new insights into the CNS regional neuropharmacokinetics of these drugs, suggesting that while the brain uptake is region-independent, the active transport mechanism enables high extracellular and intracellular drug concentrations, potentially contributing to neurotoxicity. This finding emphasizes the necessity of thorough neuropharmacokinetic evaluation and neurotoxicity profiling in the development of drugs that utilize this transport pathway.