Intelligent Drug Delivery Systems Research Articles

Construction of an intelligent pH-sensitive hydrogel drug delivery system and its application in gastric ulcer treatment

The occurrence of gastric ulcer is mainly due to the damage of gastric mucosa which leads to inward flow of gastric acid to corrode the gastric cavity, thus producing gastric fever, vomiting, loss of appetite and other adverse reactions. Prevention and treatment of such injuries are crucial. In this study, a simple and non-toxic composite hydrogel (PLGA/CMCS) was prepared through Schiff base reaction between poly(lactic-co-glycolic acid) (PLGA) and carboxymethyl cellulose (CMCS). Subsequently, compound 1 was loaded onto it to construct PLGA/CMCS@1. A series of structural characterization and performance experiments were conducted on these novel hydrogel polymers. Furthermore, we detected the gene expression level of Fas/FasL apoptotic pathway after treating the cells with different concentrations of PLGA/CMCS@1 through an ethanol-induced damaged gastric mucosal epithelial cell model. The results showed that the system was able to significantly regulate the expression of genes related to the apoptotic pathway. The system can regulate the Fas/FasL apoptosis pathway to treat gastric ulcer.

CHITOSAN AS A DRUG CARRIER

The review discusses the latest issues related to using chitosan, a biocompatible and biodegradable polymer derived from chitin, as a carrier in intelligent drug-delivery systems. The continuous development of medicine and rapid technological progress pose new challenges in designing new therapeutic agents. Chitosan has properties that make it suitable for drug-delivery applications, such as its ability to form nanoparticles and its mucoadhesion that enhance drug absorption. Chitosan can be combined with antibiotics, analgesics and other ingredients with specific properties. While chitosan is not medicinal substance, it can be a carrier in controlled drug-release systems.

Using Hybrid MnO2-Au Nanoflowers to Accelerate ROS Scavenging and Wound Healing in Diabetes

Objectives: Excessive reactive oxygen species (ROS) in diabetic wounds are major contributors to chronic wounds and impaired healing, posing significant challenges in regenerative medicine. Developing innovative drug delivery systems is crucial to address these issues by modifying the adverse microenvironment and promoting effective wound healing. Methods: Herein, we designed a novel drug delivery platform using manganese dioxide nanoflower hybridized gold nanoparticle composites (MnO2-Au) synthesized via a hydrothermal reaction, and investigated the potential of MnO2-Au nanoflowers to relieve the high oxidative stress microenvironment and regulate diabetic wound tissue healing. Results: This hybrid material demonstrated superior catalytic activity compared to MnO2 alone, enabling the rapid decomposition of hydrogen peroxide and a substantial reduction in ROS levels within dermal fibroblasts. The MnO2-Au nanoflowers also facilitated enhanced dermal fibroblast migration and Col-I expression, which are critical for tissue regeneration. Additionally, a hydrogel-based wound dressing incorporating MnO2-Au nanoflowers was developed, showing its potential as an intelligent drug delivery system. This dressing significantly reduced oxidative stress, accelerated wound closure, and improved the quality of neonatal epithelial tissue regeneration in a diabetic rat skin defect model. Conclusions: Our findings underscore the potential of MnO2-Au nanoflower-based drug delivery systems as a promising therapeutic approach for chronic wound healing, particularly in regenerative medicine.

Development of a Controllable Intelligent Drug Delivery System for Efficient Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a complex inflammatory disease of the joints, which is often accompanied by degeneration of articular cartilage and bone erosion, seriously affecting the quality of life and psychological state of patients. RA is difficult to be cured completely, and currently the main purpose of relief is through the use of anti-inflammatory and antirheumatic drugs, hormones, and biological agents. Tofacitib is a new type of small molecule inhibitor, which has a good effect in the treatment of RA. The current direct drug delivery method has serious side effects caused by the systemic distribution of the drug, so there is a need to develop an intelligent drug delivery system to realize precise treatment. In this work, tofacitib, gallic acid, targeted molecule folic acid, and Fe(III) were selected to assemble a novel type of artificial controllable nanodrug GF-TF. The self-photoacoustic/magnetic resonance imaging (self-PA/MRI) monitored the enrichment of GF-TF in the lesion in real-time, and artificially regulated the addition of deferoxamine (DFO) at the optimal enrichment. DFO strongly chelates Fe(III) in GF-TF and causes its structure to disintegrate gradually, and the self-PA/MRI signal of GF-TF became weaker while tofacitib began to be released, thus realizing the precise and artificially controlled release of the drug under the guidance of imaging. This nanodrug not only achieves efficient aggregation of drugs in inflamed joints, but also achieves real-time monitoring and precise control of drug release through self-PA/MRI, providing a new strategy for the precise treatment of RA.

Block Copolymers‐Enabled Organic–Organic Assembly for Unique Carbonaceous Micro‐/Nano‐Structures

AbstractOver the past decade, there has been growing research interest in deriving advanced carbonaceous materials with unique architectures, including diverse morphologies and compositions, from polymer‐based precursors with tailored nano/micro‐structures. The organic–organic assembly between organic molecules and block copolymers (BCPs) has emerged as a promising strategy for advancing the preformed polymers with multiple levels of complexity. This review provides a comprehensive overview of the synthesis and potential applications of unique carbonaceous nano/micro‐structures derived from commonly used organic precursors, including phenol/formaldehyde, dopamine, and biomass. It begins with a brief summary of the polymerization mechanism for each type of precursors. Following this, it details the delicate design and preparation strategies for unique polymer architectures, including the formation mechanisms of the first‐level assembly involving BCPs and organic precursors, which form composite micelles as building units, and the principles for manipulation the higher‐level assembly process of the composite micelles, illustrated with some representative examples. The review then highlights the advanced applications of these materials in heterogeneous catalysts, secondary batteries, separation, and intelligent drug delivery systems. Finally, the synthetic challenges and potential development directions of unique carbonaceous nano/micro‐structures are outlined, underscoring a pathway for developing advanced materials.

Self-Indicating Polymer Prodrug Nanoparticles for pH-Responsive Drug Delivery in Cancer Cells and Real-Time Monitoring of Drug Release.

Amphiphilic self-indicating and responsive polymer-based prodrugs have generated much interest as potential stimuli-responsive intelligent drug delivery systems (DDS) due to their ability to selectively deliver drugs to the cancer cells and to monitor real-time cellular uptake of the drug by imaging technique(s). In this direction, we have synthesized a new pH-responsive N-vinyl-2-pyrrolidone and coumarin-based fluorescent self-indicating polymeric prodrug (SIPD), poly(NVP)-b-poly(FPA.DOX-r-FPA-r-CA). This block copolymer prodrug self-assembled into stable micellar nanoparticles under physiological conditions that reduced undesirable drug leakage to normal cells but resulted in the release of the anticancer drug doxorubicin (DOX) in cancer cells because of acidic pH-induced cleavage of imine bonds between DOX and the copolymer. While the polymer was found to be highly biocompatible with both normal (HEK-293) cells and cancer (MCF-7) cells even at high concentrations by MTT assay, the polymer prodrug nanoparticles showed toxicity even higher than that of free DOX in cancer cells. Phase contrast microscopy also depicted the cytotoxic effects of the nanoparticles on cancer cells. The coumarin units present in the polymer served as a fluorescence resonance energy transfer (FRET) pair with the covalently attached DOX molecules, which was established by steady-state and time-resolved fluorescence spectroscopy. Furthermore, confocal microscopy results confirmed the FRET phenomenon, as the fluorescence intensity of coumarin in the micellar nanoparticles remained quenched initially in MCF-7 cells but recovered with time as the DOX molecules were released and gradually shifted toward the targeted nucleus. All of these studies implied that the synthesized prodrug nanoparticles may provide another viable option for delivering chemotherapeutic drugs into cancer cells with a capability of real-time monitoring of drug release.

Construction and evaluation of a folate-mediated adriamycin phosphorene thermosensitive hydrogel delivery system against osteosarcoma

The management of osteosarcoma presents a significant challenge, and the creation of an intelligent synergistic drug delivery system is broadly acknowledged as a promising approach to therapy. Hence, in this study, a temperature-sensitive hydrogel containing DOX-loaded and folic acid-modified BPNSs that can be injected was developed to enable drug release via a pH/NIR response, aimed at synergistic photothermal‒chemotherapeutic treatment of osteosarcoma. The active targeting of BPNSs-PEG-FA/DOX involved liquid-phase stripping and electrostatic adsorption, leading to the preparation of the BPNSs-PEG-FA/DOX aqueous dispersion hybrid hydrogel matrix as a BPNSs-PEG-FA/DOX@Hydrogel through a cold method. This composite hydrogel exhibits favorable through-needle properties, superior photothermal conversion efficiency, pH/NIR intelligent responsiveness, and controlled delayed-release drug release capabilities, along with favorable in vitro cellular biocompatibility. It also demonstrates effective in vitro and in vivo active targeting, controlled delayed release, and synergistic photothermal-chemotherapeutic anti-osteosarcoma activity, showing considerable promise for the treatment of superficial tumors such as osteosarcoma.

Preparation and Characterization of Oxide Nanotubes on Titanium Surface for Use in Controlled Drug Release Systems.

Preventing or treating infections at implantation sites where the risk of bacterial contamination is high requires the development of intelligent drug delivery systems. The objective of this work was to develop a production method and characterization of fourth-generation oxide nanotubes on titanium grade 4 surface as a potential drug carrier. This study focused on the anodizing process; physico-chemical characterization using FE-SEM, EDS, and FTIR; in vitro corrosion resistance in an artificial saliva solution; and determining the drug release kinetics of gentamicin sulfate using UV-VIS. The anodizing process was optimized to produce fourth-generation oxide nanotubes in a fluoride-free electrolyte, ensuring rapid growth and lack of order. Results showed that the length of the oxide nanotubes was inversely proportional to the anodizing voltage, with longer nanotubes formed at lower voltages. The nanotubes were shown to have a honeycomb structure with silver particles co-deposited on the surface for antibacterial properties and were capable of carrying and releasing the antibiotic gentamicin sulfate in a controlled manner, following Fick's first law of diffusion. The corrosion resistance study demonstrates that the oxide nanotubes enhance the corrosion resistance of the titanium surface. The oxide nanotubes show promise in enhancing osseointegration and reducing post-implantation complications.

Tumor Microenvironment Responsive RNA Drug Delivery Systems: Intelligent Platforms for Sophisticated Release.

Cancer is a significant health concern, increasingly showing insensitivity to traditional treatments, highlighting the urgent need for safer and more practical treatment options. Ribonucleic acid (RNA) gene therapy drugs have demonstrated promising potential in preclinical and clinical trials for antitumor therapy by regulating tumor-related gene expression. However, RNA's poor membrane permeability and stability restrict its effectiveness in entering and being utilized in cells. An appropriate delivery system is crucial for achieving targeted tumor effects. The tumor microenvironment (TME), characterized by acidity, hypoxia, enzyme overexpression, elevated glutathione (GSH) concentration, and excessive reactive oxygen species (ROS), is essential for tumor survival. Furthermore, these distinctive features can also be harnessed to develop intelligent drug delivery systems. Various nanocarriers that respond to the TME have been designed for RNA drug delivery, showing the advantages of tumor targeting and low toxicity. This Review discusses the abnormal changes of components in TME, therapeutic RNAs' roles, underlying mechanisms, and the latest developments in utilizing vectors that respond to microenvironments for treating tumors. We hope it provides insight into creating and optimizing RNA delivery vectors to improve their effectiveness.

A Review of Recent Advancements and Perspectives of Nanotechnology in the Application of Biomedical Imaging and Instrumentation

AbstractThe development of imaging, diagnosis, prognosis and early detection of diseases has been greatly impacted by nanotechnology by enhancing already existing clinically applicable technologies. With the help of their capacity to alter nanoparticles for molecular‐level specificity, tissue‐specific diagnosis is made possible gratitude to the unique biophysical features of the nanoparticles that enable contrast augmentation will boost biomedical imaging. The unique prospect of multiplexing is possible by the fact that minute changes in the nanoparticles’ size or composition can have significant effects on their optical, magnetic, or electrical capabilities. This article examines nanotechnology's function in biomedical imaging. In this article, the fundamentals and applications of biomedical imaging, pharmaceutical application of microbial surfactants, intelligent drug delivery systems, and green metallic nanoparticle manufacturing are all examined. The biomedical applications comprising organic (carbon nanotubes, metal oxide and liposomes) and inorganic (metal oxide, metal) nanoparticles, and materials with nanopatterns in diagnostics, biosensing, and bioimaging devices, along with drug delivery systems, are the main topics of discussion. studies conducted in vitro and in vivo have demonstrated that different nanoparticles can be utilized to detect seizures early and precisely along with to treat them successfully. To decrease the possible toxicity and enable improved target specificity, respectively, more development in the synthesis and functionalization of adaptable nanotechnologies is required.

Advances in 2,3-Dimethylmaleic Anhydride (DMMA)-Modified Nanocarriers in Drug Delivery Systems.

Cancer represents a significant threat to human health. The cells and tissues within the microenvironment of solid tumors exhibit complex and abnormal properties in comparison to healthy tissues. The efficacy of nanomedicines is inhibited by the presence of substantial and complex physical barriers in the tumor tissue. The latest generation of intelligent drug delivery systems, particularly nanomedicines capable of charge reversal, have shown promise in addressing this issue. These systems can transform their charge from negative to positive upon reaching the tumor site, thereby enhancing tumor penetration via transcytosis and promoting cell internalization by interacting with the negatively charged cell membranes. The modification of nanocarriers with 2,3-dimethylmaleic anhydride (DMMA) and its derivatives, which are responsive to weak acid stimulation, represents a significant advance in the field of charge-reversal nanomedicines. This review provides a comprehensive examination of the recent insights into DMMA-modified nanocarriers in drug delivery systems, with a particular focus on their potential in targeted therapeutics. It also discusses the synthesis of DMMA derivatives and their role in charge reversal, shell detachment, size shift, and ligand reactivation mechanisms, offering the prospect of a tailored, next-generation therapeutic approach to overcome the diverse challenges associated with cancer therapy.

Artificial Intelligence in Pharmaceutical Industry: Revolutionizing Drug Development and Delivery

Abstract: Artificial Intelligence (AI) has ushered in a profound revolution within the pharmaceutical sector, effectively streamlining the processes of drug development and delivery. The application of AI-driven tools and methodologies, including machine learning and natural language processing, in the realm of pharmaceutical research and development has yielded recent breakthroughs. This accelerated the drug discovery process by meticulously scrutinizing copious data and pinpointing potential drug targets, as expounded upon in this comprehensive review. Furthermore, AI has found utility in optimizing clinical trials, thereby refining trial designs and cost-effectiveness and bolstering patient safety. Notably, AI-based strategies are being harnessed to enhance drug delivery, fostering the creation of intelligent drug delivery systems engineered to target specific cells or organs. This results in heightened efficacy and a concomitant reduction in undesirable side effects. This review also delves into the potential biases residing within AI algorithms and the challenges associated with data quality when integrating AI into the pharmaceutical sphere. The findings of this study underscore the immense potential of artificial intelligence in reshaping the pharmaceutical industry, thereby enhancing the quality of life for patients worldwide.

Design and synthesis of drug hydrogels containing carboxymethylcellulose with honeycomb structure and pH-sensitivity as drug delivery systems for adriamycin, metformin, and naproxen

The aim of this research is to prepare and identify functionalized carboxymethylcellulose/mesoporous silica nanohydrogels (CMC/NH2-MCM-41) for obtaining a pH-sensitive system for the controlled release of drugs. The beads of CMC/NH2-MCM-41 nanocomposites were prepared by dispersing NH2-MCM-41 in a CMC polymer matrix and crosslinking with ferric ions (Fe3+). The SEM analysis of samples revealed enhancement in surface porosity of the functionalized nanohydrogel beads compared to the conventional beads. Swelling of the prepared functionalized nanohydrogels was evaluated at various pH values including pH = 7.35–7.45 (simulated body fluid or healthy cells), pH = 6 (simulated intestinal fluid), and pH = 1.5–3.5 (simulated gastric fluid). The swelling of CMC/MCM-41 and CMC/NH2-MCM-41 nanohydrogels at the pH values of simulated body fluid and simulated intestinal fluid is much higher than that of simulated gastric fluid, indicating successful synthesis of pH-sensitive nanohydrogels for drug delivery. The drug loading results showed that drug release in the CMC/NH2-MCM-41 system is much slower than that in the CMC/MCM-41 system. The results of the survival studies for the manufactured systems showed a very good biocompatibility of the designed drug delivery systems for biological applications. By coating the surface of functionalized mesopores with CMC hydrogel, we were able to develop a pH-sensitive intelligent drug delivery system.

Novel Drug Delivery Systems: An Important Direction for Drug Innovation Research and Development.

The escalating demand for enhanced therapeutic efficacy and reduced adverse effects in the pharmaceutical domain has catalyzed a new frontier of innovation and research in the field of pharmacy: novel drug delivery systems. These systems are designed to address the limitations of conventional drug administration, such as abbreviated half-life, inadequate targeting, low solubility, and bioavailability. As the disciplines of pharmacy, materials science, and biomedicine continue to advance and converge, the development of efficient and safe drug delivery systems, including biopharmaceutical formulations, has garnered significant attention both domestically and internationally. This article presents an overview of the latest advancements in drug delivery systems, categorized into four primary areas: carrier-based and coupling-based targeted drug delivery systems, intelligent drug delivery systems, and drug delivery devices, based on their main objectives and methodologies. Additionally, it critically analyzes the technological bottlenecks, current research challenges, and future trends in the application of novel drug delivery systems.

Mesoporous silica nanoparticles as a drug delivery mechanism.

Research in intelligent drug delivery systems within the field of biomedicine promises to enhance drug efficacy at disease sites and reduce associated side effects. Mesoporous silica nanoparticles (MSNs), characterized by their large specific surface area, appropriate pore size, and excellent biocompatibility, have garnered significant attention as one of the most effective carriers for drug delivery. The hydroxyl groups on their surface are active functional groups, facilitating easy functionalization. The installation of controllable molecular machines on the surface of mesoporous silica to construct nanovalves represents a crucial advancement in developing intelligent drug delivery systems (DDSs) and addressing the issue of premature drug release. In this review, we compile several notable and illustrative examples of MSNs and discuss their varied applications in DDSs. These applications span regulated and progressive drug release mechanisms. MSNs hold the potential to enhance drug solubility, improve drug stability, and mitigate drug toxicity, attributable to their ease of functionalization. Furthermore, intelligent hybrid nanomaterials are being developed, featuring programmable properties that react to a broad spectrum of stimuli, including light, pH, enzymes, and redox triggers, through the use of molecular and supramolecular switches.

A Biodegradable Nano-Drug Delivery Platform for Co-Delivery of Minocycline and Chitosan to Achieve Efficient and Safe Non-Surgical Periodontitis Therapy.

Mesoporous silica nanoparticles (MSN) are widely used as ideal nanovehicles for the delivery of chemotherapeutic drugs. However, the balance between high anti-periodontitis activity and low biotoxicity has been challenging to maintain in most relevant studies owing to the slow degradation of silica in living organisms. In this study, -responsive hydroxyapatite (HAP) was doped into the MSN skeleton, and the chemotherapeutic drug minocycline hydrochloride (MH) was loaded into the pores of MSN, forming a negatively charged drug delivery system. Cationic chitosan (COS) is a biodegradable material with high antibacterial performance and good biosafety. In this study, COS was immobilized on the surface of the drug-loaded particles through stable charge interaction to construct a composite drug delivery system (MH@MSNion@COS). In vitro and cellular experiments demonstrated effective degradation of the nanocarrier system and synchronized controlled release of the drug. Notably, compared with single MH administration, this system, in which MH and COS jointly regulated the expression levels of periodontitis- associated inflammatory factors (TNF-α, IL-6, IL-1β, and iNOS), better inhibited the progress of periodontitis and induced tissue regeneration without showing significant toxic side effects in cells. This system provides a promising strategy for the design of intelligent, efficient, and safe anti-periodontitis drug delivery systems.

Rational Design of Coordination Polymers Composited Hollow Multishelled Structures for Drug Delivery.

Multifunctional drug delivery systems (DDS) are in high demand for effectively targeting specific cells, necessitating excellent biocompatibility, precise release mechanisms, and sustained release capabilities. The hollow multishelled structure (HoMS) presents a promising solution, integrating structural and compositional design for efficient DDS development amidst complex cellular environments. Herein, starting from a Fe-based metal-organic framework (MOF), amorphous coordination polymers (CP) composited HoMS with controlled shell numbers are fabricated by balancing the rate of MOF decomposition and shell formation. Fe-CP HoMS loaded with DOX is utilized for synergistic chemotherapy and chemodynamic therapy, offering excellent responsive drug release capability (excellent pH-triggered drug release 82% within 72h at pH 5.0 solution with doxorubicin (DOX) loading capacity of 284mg g-1). In addition to its potent chemotherapy attributes, Fe-CP-HoMS possesses chemodynamic therapy potential by continuously catalyzing H2O2 to generate ·OH species within cancer cells, thus effectively inhibiting cancer cell proliferation. DOX@3S-Fe-CP-HoMS, at a concentration of 12.5µg mL-1, demonstrates significant inhibitory effects on cancer cells while maintaining minimal cytotoxicity toward normal cells. It is envisioned that CP-HoMS could serve as an effective and biocompatible platform for the advancement of intelligent drug delivery systems in the realm of cancer therapy.

Self-assembled nanoparticle-mediated cascade chemotherapy and chemodynamic therapy for enhanced tumor therapy

Chemodynamic therapy (CDT) is a non-invasive treatment strategy that aims to combat tumor growth by efficiently generating reactive oxygen species (ROS). However, the effectiveness of CDT can be limited by factors such as the availability of endogenous hydrogen peroxide (H2O2). Here, we established an intelligent nano-based drug delivery system responsive to the tumor microenvironment by self-assembling Cu2+, cisplatin, and L-histidine to form nanoparticles (Pt/CuH NPs), which can achieve the therapeutic effect of specific tumor killing by cascading chemotherapy with CDT. The Pt/CuH NPs are triggered by the acidic conditions and high glutathione (GSH) levels present in the tumor microenvironment, leading to the release of cisplatin and Cu2+. Cisplatin facilitates the production of H2O2 through a two-step enzymatic reaction, subsequently triggering ROS cascade that is amplified by CDT. Concurrently, Cu2+ consumes GSH and is reduced to Cu+, which reacts with H2O2 in an efficient Fenton-like reaction, amplifying oxidative stress and ultimately enhancing the anti-tumor therapeutic efficacy. Pt/CuH NPs demonstrated a significant cytotoxic effect on tumor cells in vitro. In vivo studies in mice indicated minimal toxic side effects at the tested dosages. The Pt/CuH NPs effectively combine chemotherapy and CDT strategies, showcasing the potential of a chemotherapy-cascading CDT approach for anti-tumor treatment.

Injectable Chitosan Hydrogels Doped with 2D Peptide Nanosheet-Drug Conjugates for Glutathione-Responsive Sustained Drug Delivery.

The development of novel and effective drug delivery systems aimed at enhancing therapeutic profile and efficacy of therapeutic agents is a critical challenge in modern medicine. This study presents an intelligent drug delivery system based on self-assembled two-dimensional peptide nanosheets (2D PNSs). Leveraging the tunable properties of amino acid structures and sequences, we design a peptide with the sequence of Fmoc-FKKGSHC, which self-assembles into 2D PNSs with uniform structure, high biocompatibility, and excellent degradability. Covalent attachment of thiol-modified doxorubicin (DOX) drugs to 2D PNSs via disulfide bond results in the peptide-drug conjugates (PDCs), which is denoted as PNS-SS-DOX. Subsequently, the PDCs are encapsulated within the injectable, thermosensitive chitosan (CS) hydrogels for drug delivery. The designed drug delivery system demonstrates outstanding pH-responsiveness and sustained drug release capabilities, which are facilitated by the characteristics of the CS hydrogels. Meanwhile, the covalently linked disulfide bond within the PNS-SS-DOX is responsive to intracellular glutathione (GSH) within tumor cells, enabling controlled drug release and significantly inhibiting the cancer cell growth. This responsive peptide-drug conjugate based on a 2D peptide nanoplatform paves the way for the development of smart drug delivery systems and has bright prospects in the future biomedicine field.

Synthesis, characterization and evaluation of a pH-responsive molecular imprinted polymer for Matrine as an intelligent drug delivery system

Abstract To address the undesirable reactions associated with matrine (MAT) injection in clinical settings, a high-loading drug delivery system (DDS) based on pH-sensitive molecularly imprinted polymer (MAT@MIPs) was prepared for the first time. The imprinted materials containing recognition sites for the matrine were formed by using carboxyl-functionalized multiwalled carbon nanotubes as a supportive matrix and dopamine as a cross-linker due to its exceptional biocompatibility. Subsequently, the optimal reaction conditions and adsorption performance of MAT@MIPs were systematically investigated. The obtained polymers were characterized and evaluated by Fourier transform infrared spectrometry, scanning electron microscopy, elemental analysis, and thermogravimetric analysis. Results indicated that the MIPs demonstrated a favorable imprinting factor (2.36) and a high binding capacity (21.48 mg·g−1) for matrine. In vitro studies, we performed cell counting kit-8 assays in HepG2 cells, then the drug delivery capabilities of MAT-loaded MIPs were validated through light microscopy analyses, and the matrine content in culture medium was quantified using ultra high-performance liquid chromatography-mass spectrum synchronously. The facile fabrication of MAT@MIPs presents a viable solution for designing high-loading and pH-responsive DDS, which can offer a novel administration approach for drugs requiring injection in clinical applications.