Responsive Drug Delivery System Research Articles

Magnetic Field/Ultrasound-Responsive Fe3O4 Microbubbles for Targeted Mechanical/Catalytic Removal of Bacterial Biofilms

Conventional antibiotics are limited by drug resistance, poor penetration, and inadequate targeting in the treatment of bacterial biofilm-associated infections. Microbubble-based ultrasound (US)-responsive drug delivery systems can disrupt biofilm structures and enhance antibiotic penetration through cavitation effects. However, currently developed US-responsive microbubbles still depend on antibiotics and lack targeting capability. In this work, magnetic field/ultrasound (MF/US)-responsive Fe3O4 microbubbles (FMB) were constructed based on Fe3O4 nanoparticles (NPs) with superparamagnetic and peroxidase-like catalytic properties. In vitro experiments demonstrated that FMB can be targeted to methicillin-resistant Staphylococcus aureus (MRSA) biofilms by the direction of MF. Upon US irradiation, FMB collapse due to inertial cavitation and generate mechanical forces to disrupt the structure of MRSA biofilms and releases Fe3O4 NPs, which catalyze the generation of reactive oxygen species (ROS) from H2O2 in the biofilm microenvironment and kill the bacteria within the biofilm. In a mouse biofilm infection model, FMB efficiently destroyed MRSA biofilms grown in subcutaneous catheters with the MF and US. Magnetic-targeted mechanical/catalytic therapy based on FMB provides a promising strategy for effectively combating bacterial biofilm infection.

A temperature-ultrasound sensitive nanoparticle delivery system for exploring central neuroinflammation mechanism in stroke-heart syndrome

BackgroundCardiovascular events secondary to stroke–collectively classified as stroke-heart syndrome–greatly impair the patient’s prognosis, however its underlying mechanism has yet to be determined. To investigate the mechanism of central neuroinflammation and its effects on stroke-heart syndrome, a temperature-ultrasound responsive brain-targeted drug delivery system, DATS/MION-LPE, was synthesized to specifically study neuroinflammation in the mouse middle cerebral artery occlusion (MCAO) model.ResultsThe specific polymer of DATS/MION-LPE can close the nanoparticle pores at 37 °C, restricting drug release in the circulation. After the nanoparticles were targeted to brains, the polymer can be cleaved under external ultrasound irradiation, reopening the nanoparticle pores and allowing drug release, therefore directly managing the neuroinflammation. After a stroke, a significant cerebral inflammation occurred, with elevated IL-1β and pyrin domain-containing 3 (NLRP3) inflammasome. Accordingly, significantly increased histone deacetylase 6 (HDAC6) and decreased sirtuin 1 (SIRT1) were observed. An antagonistic relationship between HDAC6 and SIRT1 was found, which can jointly regulate the cerebral NLRP3 expression. The systemic IL-1β and ATP levels were increased after the stroke, accompanied by a significant heart injury including contractile dysfunction, elevated IL-1β levels, and oxidative stress. Meanwhile, neuroinflammation can trigger sympathetic nervous overexcitation with associated heart damage. DATS/MION-LPE can targetedly effect on ischemic brain, exhibiting cerebral and cardiac protective effects including downregulated cerebral NLRP3 and HDAC6 expressions, upregulated SIRT1 expressions in brain, reduced IL-1β and ATP in circulation, and alleviated cardiac impairment.ConclusionThis study introduced the key role of neuroinflammation in stroke-heart syndrome and first investigated the crucial HDAC6/SIRT1-NLRP3 circuit in this process. Heart injury secondary to stroke is mediated by neuroinflammation induced systemic inflammatory responses and sympathoexcitation. DATS/MION-LPE is a unique tool and effective therapeutic agent, which provides new insights into combinational heart and cardiac protection.Graphical

A stimulus responsive microneedle-based drug delivery system for cancer therapy.

The intricate nature of the tumor microenvironment (TME) results in the inefficient delivery of anticancer drugs within tumor tissues, significantly compromising the therapeutic effect of cancer treatment. To address this issue, transdermal drug delivery microneedles (MNs) with high mechanical strength have emerged. Such MNs penetrate the skin barrier, enabling efficient drug delivery to tumor tissues. This approach enhances drug bioavailability, while also mitigating concerns such as liver and kidney toxicity associated with intravenous and oral drug administration. Notably, stimulus responsive MNs designed for drug delivery have the capacity to respond to various biological signals and pathological changes. This adaptability enables them to exert therapeutic effects within the TME, exploiting biochemical variations and tailoring treatment strategies to suit tumor characteristics. The present review surveys recent advancements in responsive MN systems. This comprehensive analysis serves as a valuable reference for the prospective application of smart MN drug delivery systems in cancer therapy.

Revolutionizing Influenza Treatment: A Deep Dive into Targeted Drug Delivery Systems.

Influenza, a highly transmissible respiratory infection caused by influenza viruses A and B, poses a persistent threat to global public health due to its high mutation rate, ability to develop resistance to existing antiviral drugs, and capacity for rapid spread. Current treatment options, including four main classes of antiviral agents-adamantanes, neuraminidase inhibitors, RNA-dependent RNA polymerase inhibitors, and polymerase acidic endonuclease inhibitors- are limited by the emergence of drug-resistant viral strains, non-specific drug distribution, and adverse side effects. Moreover, the effectiveness of traditional vaccines is often compromised by antigenic drift and shift, necessitating the development of alternative therapeutic strategies. This review comprehensively explores the potential of novel targeted drug delivery systems to address these limitations and improve influenza management. Nanotechnology-based platforms, including lipid-based, polymer-based, inorganic, and hybrid nanoparticles, offer enhanced drug delivery through improved bioavailability, targeted action, and controlled release, thus minimizing systemic toxicity and optimizing therapeutic outcomes. Inhalation delivery systems such as dry powder inhalers (DPIs), nebulizers, and nanotechnology-based inhalation formulations provide direct delivery of antiviral agents to the respiratory tract, ensuring rapid onset of action with reduced systemic side effects. Transdermal delivery methods, including microneedle patches and hydrogel-based systems, offer non-invasive alternatives that enhance patient compliance and allow for sustained drug release. Furthermore, this review discusses recent innovations, such as responsive drug delivery systems and multifunctional nanoparticles capable of simultaneous delivery of multiple therapeutic agents, representing a significant advancement in the fight against influenza. These novel approaches promise improved targeting and efficacy and enable personalized treatment strategies, enhancing patient outcomes in both seasonal flu and pandemic scenarios. Integrating these advanced drug delivery systems into clinical practice could revolutionize the management of influenza, offering a promising pathway toward more effective and safer therapies.

Reactive Oxygen Species-Responsive Pillararene-Embedded Covalent Organic Frameworks with Amplified Antimicrobial Photodynamic Therapy for the Targeted Elimination of Periodontitis Pathogens.

Reactive oxygen species (ROS)-responsive drug delivery systems possess immense potential for targeted delivery and controlled release of therapeutics. However, the rapid responsiveness to ROS and sustained release of antibacterial drugs are often limited by the challenging microenvironment of periodontitis. Integrating ROS-responsive drug delivery systems with photocatalytic technologies presents a strategic approach to overcome these limitations. Herein, a pillararene-embedded covalent organic framework (PCOF) incorporating the antibacterial prodrug thioacetal (TA) has been developed to treat periodontitis. This drug-loaded nanoplatform, namely TA-loaded PCOF, utilizes the self-amplifying ROS property to enhance therapeutic efficacy. PCOFs demonstrate exceptional photosensitivity and ROS generation capabilities when employed as drug carriers. When exposed to ROS, TA within the nanoplatform was activated and cleaved into cinnamaldehyde (CA), a highly potent antibacterial compound. By leveraging visible light to activate the site-specific infection targeting, TA-loaded PCOF effectively alleviated periodontitis, thereby advancing the field of antibacterial drug delivery systems.

ROS-Responsive Nanoparticles with Antioxidative Effect for the treatment of Diabetic Retinopathy

Diabetic retinopathy (DR) is a common microvascular complication of diabetes necessitating early intervention to impede progression, despite current clinical treatments focusing on advanced stages. Essential oils from Fructus Alpiniae zerumbet (EOFAZ) have demonstrated efficacy in protecting against high glucose (HG)-induced Müller cell activation and DR development. This study introduced a reactive oxidative species (ROS)-responsive drug delivery system (NPSPHE@EOFAZ) targeting early DR stages and oxidative stress. Our engineered nanoparticles effectively deliver EOFAZ into HG-exposed Müller cells by detecting and responding to elevated oxidative stress levels. The NPSPHE@EOFAZ significantly inhibited abnormal cell growth, reduced oxidative stress, and alleviated inflammation in vitro. In vivo experiments on diabetic mice with DR revealed that NPSPHE@EOFAZ mitigated early pathological changes by reducing oxidative stress and inflammation while also alleviating organ damage in the heart, liver, spleen, lung, and kidney. These findings underscore the potential of NPSPHE@EOFAZ as a promising antioxidant for early intervention in DR pathogenesis.

Advancements in Castor Oil‐Derived Smart Materials: A Comprehensive Mini‐Review

AbstractSmart materials encompass a class of materials capable of reorienting themselves in response to external stimuli (heat, light, and chemical), and generate smart properties such as self‐healing (SH) and shape‐memory (SM), etc. Recently, castor oil has emerged as a bio‐renewable feedstock facilitating the synthesis of smart polymers such as polyurethanes and epoxidized castor oil (CO)‐based polymers. Furthermore, fillers and nanomaterials have been added to prepare responsive materials (SH and SM) and drug delivery systems. This review delves into the recent developments in CO‐based smart materials since 2015 under thermal, photo, and chemical stimuli and their applications in coating, adhesive, soft robotics, and drug delivery. Additionally, the challenges and future scopes for the development of castor oil‐based advanced smart materials have been discussed.

Biodegradable silica gated poly (methylacrylate acid) core-shell microspheres for pH and glutathione dual responsive drug delivery

Tumor microenvironment responsive drug delivery system presents great potential in tumor-targeted drug delivery. In this study, a poly (ethylene glycol) (PEG) coated biodegradable core-shell microsphere PMAA@DOX-SiO2-PEG with a poly (methylacrylate acid) (PMAA) core and a biodegradable silica layer was prepared. Doxorubicin (DOX) was effectively loaded into the PMAA core and sealed by the silica layer with a drug loading efficiency of 15.3 %. The PEG-modified drug-loaded microspheres present high stability at simulated physiological media with minimized drug leakage (8 %, 56 h), while 80 % drug could be released within 10 h at simulated tumor environment due to the effective carrier degradation. In vitro cell experiments also confirm the good biocompatibility of the blank carrier and the effective tumor inhibition of the drug-loaded microspheres. The study is expected to further promote the development of tumor microenvironment-responsive drug delivery systems.

ROS-Responsive Nanoprobes for Bimodal Imaging-Guided Cancer Targeted Combinatorial Therapy.

Chemotherapy mediated by Reactive oxygen species (ROS)-responsive drug delivery systems can potentially mitigate the toxic side effects of chemotherapeutic drugs and significantly enhance their therapeutic efficacy. However, achieving precise targeted drug delivery and real-time control of ROS-responsive drug release at tumor sites remains a formidable challenge. Therefore, this study aimed to describe a ROS-responsive drug delivery system with specific tumor targeting capabilities for mitigating chemotherapy-induced toxicity while enhancing therapeutic efficacy under guidance of Fluorescence (FL) and Magnetic resonance (MR) bimodal imaging. Indocyanine green (ICG), Doxorubicin (DOX) prodrug pB-DOX and Superparamagnetic iron oxide (SPIO, Fe3O4) were encapsulated in poly(lactic-co-glycolic acid) (PLGA) by double emulsification method to prepare ICG/ pB-DOX/ Fe3O4/ PLGA nanoparticles (IBFP NPs). The surface of IBFP NPs was functionalized with mammaglobin antibodies (mAbs) by carbodiimide method to construct the breast cancer-targeting mAbs/ IBFP NPs (MIBFP NPs). Thereafter, FL and MR bimodal imaging ability of MIBFP NPs was evaluated in vitro and in vivo. Finally, the combined photodynamic therapy (PDT) and chemotherapy efficacy evaluation based on MIBFP NPs was studied. The multifunctional MIBFP NPs exhibited significant targeting efficacy for breast cancer. FL and MR bimodal imaging clearly displayed the distribution of the targeting MIBFP NPs in vivo. Upon near-infrared laser irradiation, the MIBFP NPs loaded with ICG effectively generated ROS for PDT, enabling precise tumor ablation. Simultaneously, it triggered activation of the pB-DOX by cleaving its sensitive moiety, thereby restoring DOX activity and achieving ROS-responsive targeted chemotherapy. Furthermore, the MIBFP NPs combined PDT and chemotherapy to enhance the efficiency of tumor ablation under guidance of bimodal imaging. MIBFP NPs constitute a novel dual-modality imaging-guided drug delivery system for targeted breast cancer therapy and offer precise and controlled combined treatment options.

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.

Recent Progress in Multifunctional Stimuli-Responsive Combinational Drug Delivery Systems for the Treatment of Biofilm-Forming Bacterial Infections.

Drug-resistant infectious diseases pose a substantial challenge and threat to medical regimens. While adaptive laboratory evolution provides foresight for encountering such situations, it has inherent limitations. Novel drug delivery systems (DDSs) have garnered attention for overcoming these hurdles. Multi-stimuli responsive DDSs are particularly effective due to their reduced background leakage and targeted drug delivery to specific host sites for pathogen elimination. Bacterial infections create an acidic state in the microenvironment (pH: 5.0-5.5), which differs from normal physiological conditions (pH: 7.4). Infected areas are characterized by the overexpression of hyaluronidase, gelatinase, phospholipase, and other virulence factors. Consequently, several effective stimuli-responsive DDSs have been developed to target bacterial pathogens. Additionally, biofilms, structured communities of bacteria encased in a self-produced polymeric matrix, pose a significant challenge by conferring resistance to conventional antimicrobial treatments. Recent advancements in nano-drug delivery systems (nDDSs) show promise in enhancing antimicrobial efficacy by improving drug absorption and targeting within the biofilm matrix. nDDSs can deliver antimicrobials directly to the biofilm, facilitating more effective eradication of these resilient bacterial communities. Herein, this review examines challenges in DDS development, focusing on enhancing antibacterial activity and eradicating biofilms without adverse effects. Furthermore, advances in immune system modulation and photothermal therapy are discussed as future directions for the treatment of bacterial diseases.

Synthesis of Novel Anticancer Drugs Derived from 4‐nitrobenzaldehyde, and Investigation of Responsive Drug Delivery Systems Based on Carbon Quantum Dots.

AbstractThe present work describes the synthesis two novel derivatives of 4‐nitrobenzaldehyde through a single pot microwave assisted green synthetic method and the characterization of the synthesized drugs using UV, IR,1HNMR, Mass spectra and CHN analysis. The structure optimization of the synthesized anticancer agents was carried out using Gaussian 9. Also carbon quantum dots (CQDs) derived from amino acid precursors were synthesized (Cystine and threonine) by microwave assisted method, followed by the integration of CQDS together with 4‐nitrobenzaldehyde and its novel derivatives. The drugs were subjected to targeted drug delivery applications in cancer cell lines (PC3) The MTT assay results revealed that the CQDs conjugated with 4‐nitrobenzaldehye (D1) and one of the derivatives (D3) exhibited greater cytotoxic effects on PC3 cells compared to L929 cells. The outcomes demonstrated that this novel derivative could kill cancer cells as effectively as 4‐nitrobenzaldehyde conjugated with CQDs. Also, the potential cytotoxicity of drugs D1 and D3 were further confirmed by the apoptosis assay using flow cytometry, which also explains that apoptosis is the mechanism underlying cell death in PC3 cancer cells. The autofluorescence test were also carried out in PC3 cells lines and the drugs D1 and D3 showed significant autofluorescence in PE−A (29.9 % and 34.7 %), in Alexa Fluor‐488 (32.6 % and61.1 %) and in Bv510‐A (16.6 % and 23.2 %) respectively. Thus, the synergistic effect of CQDs together with 4‐nitrobenzaldehyde and its derivative drug D3 are indeed a promising medication towards the localized drug delivery applications in prostate cancer cells as well as the autofluorescence results will explore novel arenas in bioimaging applications.

Designing Dual-Responsive Drug Delivery Systems: The Role of Phase Change Materials and Metal-Organic Frameworks.

Stimuli-responsive drug delivery systems (DDSs) offer precise control over drug release, enhancing therapeutic efficacy and minimizing side effects. This review focuses on DDSs that leverage the unique capabilities of phase change materials (PCMs) and metal-organic frameworks (MOFs) to achieve controlled drug release in response to pH and temperature changes. Specifically, this review highlights the use of a combination of lauric and stearic acids as PCMs that melt slightly above body temperature, providing a thermally responsive mechanism for drug release. Additionally, this review delves into the properties of zeolitic imidazolate framework-8 (ZIF-8), a stable MOF under physiological conditions that decomposes in acidic environments, thus offering pH-sensitive drug release capabilities. The integration of these materials enables the fabrication of complex structures that encapsulate drugs within ZIF-8 or are enveloped by PCM layers, ensuring that drug release is tightly controlled by either temperature or pH levels, or both. This review provides comprehensive insights into the core design principles, material selections, and potential biomedical applications of dual-stimuli responsive DDSs, highlighting the future directions and challenges in this innovative field.

Disulfide bonds as a molecular switch of enzyme-activatable anticancer drug precise release for fluorescence imaging and enhancing tumor therapy

Enzyme-activatable drug delivery systems have been developed for cancer diagnosis and therapy. However, targeted intracellular drug delivery is a challenge for precisely tumor imaging and therapy due to the increased stability of copolymer nanoparticles (NPs) is accompanied by a notable decrease in enzyme degradation. Herein, disulfide bond was designed as an enzyme-activatable molecular switch of SS-P(G2)2/DOX NPs. The copolymer NPs consists of polyvinylpyrrolidone (PVP) with disulfide bonds in the center and enzyme-degradable peptide dendrites (Phe-Lys) to form dendritic-linear-dendritic triblock copolymers (TBCs). The amphiphilic TBCs could be split into two identical amphiphilic diblock copolymers (DBCs) by glutathione (GSH) in cancer cells specifically while maintaining the same hydrophilic-lipophilic equilibrium. This structural transformation significantly reduced the stability of copolymer NPs and enhanced sensitivity of DOX release by cathepsin B-activated. Subsequently, the released DOX acted as an indicator of fluorescence imaging and chemotherapy drug for cancer cells. The polymeric NPs achieved excellent drug-loaded stability and prolonged blood circulation in vivo, and realized fluorescence imaging and specific cancer cell killing capabilities by responding to the overexpression of GSH and cathepsin B in tumor cells. Furthermore, the copolymer NPs demonstrated excellent blood compatibility and biosafety. Therefore, a novel strategy based on one tumor marker acting as the switch for another tumor microenvironment responsive drug delivery system could be designed for tumor intracellular imaging and chemotherapy.

The application of phenylboronic acid pinacol ester functionalized ROS-responsive multifunctional nanoparticles in the treatment of Periodontitis

Periodontitis is an inflammatory disease induced by the complex interactions between the host immune system and the microbiota of dental plaque. Oxidative stress and the inflammatory microenvironment resulting from periodontitis are among the primary factors contributing to the progression of the disease. Additionally, the presence of dental plaque microbiota plays a significant role in affecting the condition. Consequently, treatment strategies for periodontitis should be multi-faceted. In this study, a reactive oxygen species (ROS)-responsive drug delivery system was developed by structurally modifying hyaluronic acid (HA) with phenylboronic acid pinacol ester (PBAP). Curcumin (CUR) was encapsulated in this drug delivery system to form curcumin-loaded nanoparticles (HA@CUR NPs). The release results indicate that CUR can be rapidly released in a ROS environment to reach the concentration required for treatment. In terms of uptake, HA can effectively enhance cellular uptake of NPs because it specifically recognizes CD44 expressed by normal cells. Moreover, HA@CUR NPs not only retained the antimicrobial efficacy of CUR, but also exhibited more pronounced anti-inflammatory and anti-oxidative stress functions both in vivo and in vitro. This provides a good potential drug delivery system for the treatment of periodontitis, and could offer valuable insights for dental therapeutics targeting periodontal diseases.

Facile synthesis and polymerization of 1,4,5-oxadithiepan-2-one for disulfide-based redox-responsive drug delivery

Chemotherapeutic drugs have been shown to be promising for the treatment of tumors, however, they are associated with several disadvantages including low aqueous solubility, non-specificity, and poor plasma stability. Hence, they accumulate in the health organs and create several adverse effects. Drug encapsulated stimuli-responsive nanoparticles bearing redox-responsive disulfide linkages have emerged as promising delivery vehicle to address these limitations. A glutathione (GSH) responsive disulfide-based drug delivery system based on a polyethylene glycol methyl ether (PEGME) and a polydisulfide (PDS) diblock copolymer has been developed. The cyclic lactone containing a disulfide link, 1,4,5-oxadithiepan-2-one, was prepared using a thiol-free method utilizing the reaction of 2-bromoethyl bromoacetate with sodium disulfide. Ring-opening polymerization (ROP) of 1,4,5-oxadithiepan-2-one using 1-butanol in the presence of Sn(oct)2 generated the homopolymer PDS whereas the diblock copolymer PEGME-b-PDS was obtained when PEGME was used as a macroinitiator. In aqueous solution, PEGME-b-PDS self-assembled into spherical-shaped micelles with a hydrodynamic radius of 146 and 116 nm as measured by Field-emission Scanning Electron Microscopy (FESEM) and Dynamic Light Scattering (DLS), respectively. At pH = 7.4, a Doxorubicin (DOX) loaded PEGME-b-PDS micelle showed a cumulative release of ∼98.2, ∼9.9, and ∼1.9 % in presence of 2 mM, 2 μM DTT and in absence of DTT, respectively clearly demonstrating the redox responsiveness of the PDS block. The best fit of kinetic data using with the Korsmeyer-Peppas model suggests a Fickian diffusion as well as chain-relaxation controlled drug release process. DOX loaded micelles and free DOX displayed similar cytotoxicity towards both 4T1 and MCF-7 cells indicating that the encapsulation inside the micelle did not affect the anticancer efficacy of the drug. The drug loaded micelle showed higher cellular uptake than free DOX in both 4T1 and MCF-7 lines and lower cellular uptake than free DOX in 3T3-L1 cell lines. This polymeric micellar nanoparticle may be further exploited for encapsulation of other hydrophobic drugs.

Self-adaptive pyroptosis-responsive nanoliposomes block pyroptosis in autoimmune inflammatory diseases

Nanoliposomes have a broad range of applications in the treatment of autoimmune inflammatory diseases because of their ability to considerably enhance drug transport. For their clinical application, nanoliposomes must be able to realize on-demand release of drugs at disease sites to maximize drug-delivery efficacy and minimize side effects. Therefore, responsive drug-release strategies for inflammation treatment have been explored; however, no specific design has been realized for a responsive drug-delivery system based on pyroptosis-related inflammation. Herein, we report a pioneering strategy for self-adaptive pyroptosis-responsive liposomes (R8-cardiolipin-containing nanoliposomes encapsulating dimethyl fumarate, RC-NL@DMF) that precisely release encapsulated anti-pyroptotic drugs into pyroptotic cells. The activated key pyroptotic protein, the N-terminal domain of gasdermin E, selectively integrates with the cardiolipin of liposomes, thus forming pores for controlled drug release, pyroptosis, and inflammation inhibition. Therefore, RC-NL@DMF exhibited effective therapeutic efficacies to alleviate autoimmune inflammatory damages in zymosan-induced arthritis mice and dextran sulfate sodium-induced inflammatory bowel disease mice. Our novel approach holds great promise for self-adaptive pyroptosis-responsive on-demand drug delivery, suppressing pyroptosis and treating autoimmune inflammatory diseases.

Marine polysaccharides: Biological activities and applications in drug delivery systems

The ocean is the common home of a large number of marine organisms, including plants, animals, and microorganisms. Researchers can extract thousands of important bioactive components from the oceans and use them extensively to treat and prevent diseases. In contrast, marine polysaccharide macromolecules such as alginate, carrageenan, Laminarin, fucoidan, chitosan, and hyaluronic acid have excellent physicochemical properties, good biocompatibility, and high bioactivity, which ensures their wide applications and strong therapeutic potentials in drug delivery. Drug delivery systems (DDS) based on marine polysaccharides and modified marine polysaccharide molecules have emerged as an innovative technology for controlling drug distribution on temporal, spatial, and dosage scales. They can detect and respond to external stimuli such as pH, temperature, and electric fields. These properties have led to their wide application in the design of novel drug delivery systems such as hydrogels, polymeric micelles, liposomes, microneedles, microspheres, etc. In addition, marine polysaccharide-based DDS not only have smart response properties but also can combine with the unique biological properties of the marine polysaccharide base to exert synergistic therapeutic effects. The biological activities of marine polysaccharides and the design of marine polysaccharide-based DDS are reviewed. Marine polysaccharide-based responsive DDS are expected to provide new strategies and solutions for disease treatment.

Zinc-doped hydroxyapatite as a pH responsive drug delivery system for anticancer drug 6-mercaptopurine.

6-Mercaptopurine (6MP) is commonly used in the treatment of acute lymphoblastic leukemia as an important agent in maintenance therapy. Despite its therapeutic benefits, 6MP has some limitations during therapy. Taking into account the disadvantages during 6MP therapy, there is a great need to create an appropriate delivery system for this drug. 6MP contains in its structure nitrogen and sulfur atoms capable of forming coordination compounds with metal ions, for example zinc. Therefore, in this work, we prepared biocompatible hydroxyapatite (HAp) doped with zinc ions, and used it as a carrier for 6MP. Doped HAp has not been used as a carrier for this drug before. The work proved that the prepared carrier-drug system has a particle size of about 130 nm, which indicates its potential for intravenous delivery. In addition, in an acidic environment (imitating cancer cells), the carrier agglomerates allow targeted release of the drug. The drug is evenly distributed, which indicates that the doses released from it will always be comparable. The release of the drug in a neutral environment is long-lasting in controlled doses, whereas in an acidic environment it is immediate. The obtained results indicate the high potential of the material in both slow-release and cancer-targeted release of 6MP.

Leveraging novel innovative thermoresponsive polymers in microneedles for targeted intradermal deposition

Microneedles have garnered considerable attention over the years as a versatile pharmaceutical platform that could be leveraged to deliver drugs into and across the skin. In the current work, poly (N-isopropylacrylamide) (PNIPAm) is synthesized and characterized as a novel material for the development of a physiologically responsive microneedle-based drug delivery system. Typically, this polymer transitions reversibly between a swell state at lower temperatures and a more hydrophobic state at higher temperatures, enabling precise drug release. This study demonstrates that dissolving microneedles patches made from PNIPAm, incorporating BIS-PNIPAm, a crosslinked polymer variant, exhibit enhanced mechanical properties, evident from a smaller height reduction in microneedle (∼10 %). Although microneedles using PNIPAm alone were achievable, it displayed poor mechanical strength, requiring the inclusion of additional polymeric excipients like PVA to enhance mechanical properties. In addition, the incorporation of a thermoresponsive polymer did not have a significant (p > 0.05) impact on the insertion properties of the needles as all formulations inserted to a similar depth of 500 µm into ex vivo skin. Furthering this, the needles were loaded with a model payload, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindodicarbocyanine perchlorate (DID) and the deposition of the cargo was monitored via multiphoton microscopy that showed that a deposit is formed at a depth of ≈200 µm. Also, it was revealed that crosslinked-PNIPAm (Bis-PNIPAm) formulations exhibited notable skin accumulationof the dye only after 4 h, independent of the excipient matrix used. This phenomenon was absent in non-crosslinked PNIPAm formulations, indicating a deposit formation in Bis-PNIPAm microneedle formulation. Collectively, this proof-of-concept study has advanced our understanding on the possibility to use PNIPAm for dissolving microneedle fabrication which could be harnessed for the deposition of nanoparticles into the dermis, for extended drug release within the skin.