Multifunctional Drug Delivery System Research Articles

Therapeutic Potential of Hydrogel Based Sodium Alginate and Chitosan as A Multifunctional Drug Delivery System for Atopic Dermatitis

Therapeutic Potential of Hydrogel Based Sodium Alginate and Chitosan as A Multifunctional Drug Delivery System for Atopic Dermatitis

Exosomes-based dual drug-loaded nanocarrier for targeted and multiple proliferative vitreoretinopathy therapy.

Proliferative vitreoretinopathy (PVR) is a common cause of vision loss after retinal reattachment surgery and ocular trauma. The key pathogenic mechanisms of PVR development include the proliferation, migration and epithelial-mesenchymal transition (EMT) of retinal pigment epithelial cells (RPEs) activated by the growth factors and cytokines after surgery. Although some drugs have been tried in PVR treatments as basic investigations, the limited efficacy remains an obstacle, which may be due to the single pharmacological action and lack of targeting. Herein, the anti-proliferative Daunorubicin and anti-inflammatory Dexamethasone were co-loaded in the RPEs-derived exosomes (Exos), obtaining an Exos-based dual drug-loaded nanocarrier (Exos@D-D), and used for multiple PVR therapy. Owing to the advantages of homologous Exos and the dual drug loading, Exos@D-D showed good RPEs targeting as well as improved uptake efficiency, and could inhibit the proliferation, migration, as well as EMT of RPEs effectively. The animal studies have also demonstrated that Exos@D-D effectively inhibits the production of proliferative membranes and prevents the further development of inflammation, shows significant therapeutic effects on PVR and good biocompatibility. Such Exos-based dual drug-loaded nanocarrier investigation not only provides a promising approach for multifunctional exosome drug delivery systems construction, but also has great potential in PVR clinical therapy application.

A Novel Lipopeptide-Functionalized Metal-Organic Framework for Periodontitis Therapy through the Htra1/FAK/YAP Pathway.

Periodontitis is a chronic inflammatory disease characterized by plaque accumulation, resulting in immune microenvironment disorders and resorption of alveolar bone. To promote bone healing under inflammatory environments, a functional biomaterial based on disease pathophysiology is designed. A novel fatty acid C10-modified polypeptide, C10-KR8, is discovered to have excellent abilities in modulating macrophage repolarization and promoting bone regeneration in periodontitis. To build a multifunctional material localized drug delivery system, C10-KR8@ZIF-8 (C10-KR8-loaded zeolitic imidazolate framework-8) nanoparticles are constructed to sustainedly release the C10-KR8 peptide and Zn elements. By synergistic effects of providing a dynamic immuno-modulatory environment and promoting osteogenesis under pathological conditions, the obtained pH-responsive nanoparticles display excellent bone regeneration capability. Furthermore, coimmunoprecipitation/liquid chromatography-tandem mass spectrometry analysis and proteomics analysis revealed that the C10-KR8 peptide directly interacts with the high-temperature requirement protein A1 (Htra1), and C10-KR8@ZIF-8 nanoparticles promote the osteogenic differentiation of bone mesenchymal stem cells by activating the focal adhesion kinase (FAK)/phosphatidylinositide 3-kinase (PI3K)/AKT pathway and enhancing the nuclear localization of Yes-associated protein (YAP). Taken together, this study demonstrates C10-KR8 peptide regulate osteoimmunology and bone regeneration by Htra1/FAK/YAP pathway and that ZIF-8-based peptide loading platform is a promising strategy for periodontitis.

Responsive ZIF-90 nanocomposite material: targeted delivery of 10-hydroxycamptothecine to enhance the therapeutic effect of colon cancer (HCT116) cells.

There is significant value in developing multifunctional drug delivery systems with high therapeutic efficiency for diagnosing and treating tumors. In this study, we synthesized the ATP-triggered and pH-sensitive material ZIF-90 using the liquid-phase diffusion method. This was done to load 10-hydroxycamptothecin (HCPT), and the FA-PEG-NH2 conjugate was synthesized through an amidation reaction. We further modified the HCPT@ZIF-90 nanocomposite by employing the Schiff base reaction to create the HCPT@ZIF-90-PEG-FA nanomaterial. Drug loading test results revealed a high HCPT drug loading of up to 22.3% by weight. In the drug release experiment, the cumulative drug release of HCPT@ZIF-90 nanomaterials in pH 5.4 and ATP solutions was the highest after 72 hours. The active targeted delivery of FA and the dual-responsive release of HCPT by ZIF-90 significantly enhanced the therapeutic effect of HCPT@ZIF-90-PEG-FA on human colon cancer cells (HCT116). In the cytotoxicity test, when 100 μg mL-1 of HCPT@ZIF-90-PEG-FA was incubated with cells, the cell survival rate was 16.61 ± 1.19%, significantly lower than that of the other experimental groups. This result indicates that HCPT@ZIF-90-PEG-FA exhibits excellent anti-tumor activity. Cell cycle experiments have shown that HCPT@ZIF-90-PEG-FA may inhibit the proliferation of cancer cells by blocking DNA synthesis and halting cell cycle progression. Cell uptake experiments showed that HCPT@ZIF-90-PEG-FA was mainly present in the cytoplasm of HCT1116 cells, indicating successful cellular entry of the drug to exert its therapeutic effect. In vivo experiments also demonstrated that HCPT@ZIF-90-PEG-FA nanomaterials can effectively eradicate HCT116 tumors. The utilization of the nano-drug carrier ZIF-90, along with the modification with PEG-FA, notably improved the therapeutic efficacy of HCPT. These results suggest that the system, with its active targeted delivery of FA and dual-responsive release of HCPT, could present a novel strategy for treating human colorectal cancer.

Tetramethylpyrazine-loaded liposomes surrounded by hydrogel based on sodium alginate and chitosan as a multifunctional drug delivery System for treatment of atopic dermatitis

Tetramethylpyrazine (TMP) has low bioavailability due to its fast metabolism and short half-life, which is not conducive to transdermal treatment of atopic dermatitis (AD). Therefore, in this study, TMP was encapsulated into liposomes (Lip) by film dispersion method, and then the surface of Lip was modified by sodium alginate (ALG) and chitosan (CS). The tetramethylpyrazine-loaded liposomes in sodium alginate chitosan hydrogel called T-Lip-AC hydrogel. In vitro experiments, we found that T-Lip-AC hydrogel not only had the antibacterial effect of CS, but also enhanced the anti-inflammatory and antioxidant effects of TMP. In addition, T-Lip-AC hydrogel could also provide a moist healing environment for AD dry skin and produce better skin permeability, and can also achieve sustained drug release, which is conducive to the treatment of AD. The lesions induced by 1-chloro-2,4-dinitrobenzene were used as the AD lesions model to test the therapeutic effect of the T-Lip-AC hydrogel on AD in vivo. The studies have showed that T-Lip-AC hydrogel could effectively promote wound healing. Therefore, we have developed a T-Lip-AC hydrogel as multifunctional hydrogel drug delivery system, which could become an effective, safe and novel alternative treatment method for treating AD.

The Effect of Copolymer-Based Nanoparticle Composition (MEO2MA-OEGMA) on the Release Profile of Doxorubicin In Vitro

The release of drugs from core/shell nanoparticles (NPs) is a crucial factor in ensuring high reproducibility, stability, and quality control. It serves as the scientific basis for the development of nanocarriers. Several factors, such as composition, composition ratio, ingredient interactions, and preparation methods, influence the drug release from these carrier systems. The objective of our study was to investigate and discuss the relationship between modifications of core/shell NPs as multifunctional drug delivery systems and the properties and kinetics of drug release using an in vitro drug release model. In this paper, we prepared four core/shell NPs consisting of a superparamagnetic iron oxide NPs (Fe3−δO4) core encapsulated by a biocompatible thermo-responsive copolymer, poly(2-(2-methoxy) ethyl methacrylate-oligo (ethylene glycol) methacrylate) or P(MEO2MAx-OEGMA100−x) (where x and 100 − x represented the molar fractions of MEO2MA and OEGMA, respectively), and loaded with doxorubicin (DOX). Colloidal behavior measurements in water and PBS as a function of temperature showed an optimization of the lower critical solution temperature (LCST) depending on the molar fractions of MEO2MA and OEGMA used to form each NPs. In vitro studies of doxorubicin release as a function of temperature demonstrated a high control of release based on the LCST. A temperature of approximately 45 °C for 60 h was sufficient to release 100% of the DOX loaded in the NPs for each sample. In conclusion, external stimuli can be used to modulate the drug release behavior. Core/shell NPs hold great promise as a technique for multifunctional drug delivery systems.

Hierarchical Microcarriers Loaded with Peptide Dendrimer‐Grafted Methotrexate for Rheumatoid Arthritis Treatment

Rheumatoid arthritis (RA) is one of the leading causes of disability due to the autoimmune destruction of synovial joints. Great efforts have been put into developing multifunctional drug delivery systems for delaying the progression of RA. Herein, a novel locally injectable, hierarchically structured delivery system with a hyaluronic acid (HA) microparticle and an MTX‐conjugated nanoparticle for promoted RA treatment is proposed. In this system, MTX is chemically grafted onto a peptide dendrimer‐based nanoparticle (G‐MTX). These nanoparticles are encapsulated inside HA microparticles (H‐G‐MTX) using microfluidics to realize the system. The G‐MTX can be released from the degradable HA microparticles in the acidic environment of inflamed RA joints. As the G‐MTX shows an enhanced intracellular delivery of the conjugated MTX, the H‐G‐MTX can reverse the dominant macrophage phenotype from M1 to M2. Through a collagen‐induced arthritis (CIA) rat model, the great therapeutic outcomes of this hierarchically structured delivery system are demonstrated, including inflammation reduction, cartilage protection, and bone mineral density promotion. These results indicate that the proposed hierarchical delivery system has potential clinical value in the treatment of RA and other diseases.

In situ autophagy regulation in synergy with phototherapy for breast cancer treatment

Autophagy is an important factor in reducing the efficacy of tumor phototherapy (including PTT and PDT). Accurate regulation of autophagy in tumor cells is a new strategy to improve the anti-tumor efficiency of PTT/PDT. This project intended to construct a tumor-activated autophagy regulator to efficiently block PTT/PDT-induced autophagy and realize synergistic sensitization to tumor phototherapy. To achieve this goal, we first synthesized TRANSFERRIN (Tf) biomimetic mineralized nano-tellurium (Tf-Te) as photosensitizer and then used disulfide bond reconstruction technology to induce Tf-Te self-assembly. The autophagy inhibitor hydroxychloroquine (HCQ) and iron ions carried by Tf were simultaneously loaded to prepare a tumor-responsive drug reservoir Tf-Te/HCQ. After entering breast cancer cells through the “self-guidance system”, Tf-Te/HCQ can generate hyperpyrexia and ROS under NIR laser irradiation, to efficiently induce PTT/PDT effect. Meanwhile, the disulfide bond broke down in response to GSH, and the nanoparticles disintegrated to release Fe2+ and HCQ at fixed points. They simultaneously induce lysosomal alkalinization and increased osmotic pressure, effectively inhibit autophagy, and synergistically enhance the therapeutic effect of phototherapy. In vivo anti-tumor results have proved that the tumor inhibition rate of Tf-Te/HCQ can be as high as 88.6% on 4T1 tumor-bearing mice. This multifunctional drug delivery system might provide a new alternative for more precise and effective tumor phototherapy.

Near‐Infrared Emission‐Cyanine 5.5 and Doxorubicin Loaded Magnetite Nanoparticles for Dual In Vivo Magnetic Resonance and Biodistribution Imaging

AbstractThe in vivo imaging of the drug distribution during cancer treatment plays an important role in helping physicians and pharmacists to monitor the progress of treatment and improve the effectiveness of therapy. Our goal in this work was to prepare a multifunctional nano drug delivery system that not only co‐loaded iron oxide nanoparticles (Fe3O4 NPs) and Doxorubicin (Dox) but also attached the near‐infrared fluorescent agent Cyanine 5.5 based on poly(lactide)‐tocopheryl polyethylene glycol 1000 succinate (PLA‐TPGS) copolymer. Cyanine 5.5 was attached to the surface Fe3O4 NPs via the NH−CO chemical bond, followed by co‐loading of Dox onto the PLA‐TPGS copolymer by the emulsion solvent evaporation method. The structural, morphological, dimensional, stability, and optical‐magnetic properties of the as‐synthesized nanosystem were fully characterized. From the drug‐released study, the prolonged release of Dox accelerated with increasing acidic conditions (at pH 5.0 and 6.5), while a slow release was observed at pH 7.4. Through the MTT assay, the nanosystem had cellular toxicity against Hep−G2 and HeLa cell lines with low IC50 values of 0.42 and 0.78 μg.mL−1 in terms of Dox concentration, respectively. At a magnetic field of 7 T, this nanosystem also exhibited a high r2/r1 ratio of 164.5 and a strong contrast magnetic resonance (MR) image in the liver. In vivo biodistribution studies revealed that the highest fluorescence intensity achived in the liver after 6 h, and the nanosystem was eliminated from the body after at least 24 h. Collectively, these results demonstrated that the PLA‐TPGS‐Fe3O4‐Cyanine 5.5‐Dox nanosystem is a good candidate for simultaneously increasing contrast for MR and near‐infrared fluorescence imaging.

A multifunctional drug delivery cargo: Folate-driven gold nanoparticle-vitamin B complex for next-generation drug delivery

The gold nanoparticles have manifold applications as drug delivery agents. The larger surface-to-volume ratio of the gold nanoparticles is the primary reason for their high drug-loading efficiency. Currently, their application is transitioning into nuclear medicines and as a theranostic assay of biological tissues. Bioactive gold nanoparticles have the potential to bind with growth factors such as Vitamins to regulate the cellular functions of different organs of the human body. The present study focuses on the formation of folate-functionalized gold nanoparticles conjugated Vitamin B complex. AuNPs were fabricated using thiol-linkage to conjugate folic acid and Vitamin B complex using heterobifunctional PEG derivative and characterized by UV–visible spectroscopy, FTIR, XRD analysis and Dynamic light scattering DLS. Thiol-linked folate functionalized AuNP-Vitamin B complex can act as a selective targeting molecule and exert a synergistic therapeutic effect as a multifunctional drug delivery system in nanomedicines.

Degradation Kinetics of Disulfide Cross-Linked Microgels: Real-Time Monitoring by Confocal Microscopy.

Although biodegradable microgels represent a useful drug delivery system, questions remain regarding the kinetics of gel degradation and subsequent drug release. Spherical microgels (~Ø10-300 µm) were synthesized using an inverse suspension polymerization method. Specifically, acrylamide and acrylonitrile monomers were thermally co-polymerized with N,N'-bis(acryloyl)cystamine as a cross-linker with disulfide bridges. The kinetics and mechanism of degradation of these cross-linked, degradable, fluorescently labeled microgels (PAAm-AN-BAC-FA) were quantitatively studied under confocal microscopy at various concentrations of glutathione (reducing agent) ranging from 0.06 to 91.8 mM. It was found that polymer network degradation via the cleavage of disulfide bonds was accompanied by two overlapping processes: diffusion-driven swelling and dissolution-driven erosion. A slow increase in microgel size (swelling) resulted from partial de-cross-linking in the bulk of the microgel, whereas a faster decrease in fluorescence intensity (erosion) resulted from the complete cleavage of disulfide bonds and the release of uncleaved polymeric chains from the microgel immediate surface into the solution. Swelling and erosion exhibited distinct kinetics and characteristic times. Importantly, the dependence of kinetics on glutathione concentration for both swelling and erosion suggests that degradation would occur faster in cancer cells (higher concentration of reductants) than in normal cells (lower concentration of reductants), such that drug release profiles would be correspondingly different. A greater comprehension of microgel degradation kinetics would help in (i) predicting the drug release profiles for novel multifunctional drug delivery systems and (ii) using redox-sensitive degradable hydrogel particles to determine the concentrations of reducing agents either in vitro or in vivo.

Valine conjugated polymeric nanocarriers for targeted co-delivery of rivastigmine and quercetin in rat model of Alzheimer disease

Multifunctional nanocarriers are increasingly promising for disease treatment aimed at finding effective therapy and overcoming barriers in drug delivery. Herein, valine conjugated chitosan (VLCS) was used for surface modification of nanocarriers (NCs) based on Poly (ε-caprolactone)-Poly (ethylene glycol)-Poly (ε-caprolactone) (PCL-PEG-PCL) triblock copolymers (NCs@VLCS). The nanocarriers were co-loaded with rivastigmine (RV) and quercetin (QT) to yield the final RV/QT-NCs@VLCS as a multifunctional nanocarrier for Alzheimer’s disease (AD) treatment. The large amino acid transporter 1 (LAT-1) was selected for the direction of the NCs to the brain. The biocompatibility of the nanocarrier was studied in HEK-293 and SH-SY5Y cells and rats. The Morris water maze test demonstrated a faster regain of memory loss with RV/QT-NCs@VLCS compared to the other groups. Furthermore, RV/QT-NCs@VLCS and RV/QT-NCs improved GSH depletion induced by scopolamine (SCO), with RV/QT-NCs@VLCS having a superior effect. The real-time PCR analysis revealed that co-delivery of RV and QT by NCs@VLCS showed significantly higher efficacy than sole delivery of RV. RV/QT-NCs@VLCS treatment also modulated the expression of BDNF, ACHE, and TNF-α. The findings revealed that NCs@VLCS co-loaded with RV and QT, significantly increased efficacy relative to the single use of RV and could be considered a potent multifunctional drug delivery system for Alzheimer’s treatment.

Engineered Extracellular Vesicles to Enhance Antigen Presentation for Boosting Light-Driven Tumor Immunotherapy.

Extracellular vesicles (EVs) have emerged as potential tools for tumor-target therapy accompanied with activating anticancer immune responses by serving as an integrated platform, but usually suffered from the limited cross presentation of tumor-associated antigen by dendritic cells (DCs). Here, a straightforward engineering strategy to construct heat shock proteins 70 (HSP70) highly expressed EVs incapsulated with Te nanoparticles (Te@EVsHSP70 ) for tumor photothermal therapy triggering improved immunotherapy is proposed. Tumor cells are firstly used as bioreactors for intracellular synthesis of Te nanoparticles, and NIR irradiation is subsequently introduced to upregulate the expression of HSP70 to give engineered Te@EVsHSP70 through exocytosis. Te@EVsHSP70 exhibits excellent photothermal performance and enhanced tumor antigen capture capability, which induces significant immunogenic death of tumor cells and improves DCs maturation both in vitro and in vivo. Thus, the engineered EVs demonstrate superior antitumor efficacy through photothermal effect and following provoked antitumor immune responses. This work provides a facile method to fabricate multifunctional EVs-based drug delivery system for improving photothermal-triggered tumor immunotherapy.

Bio-based Carbon dots Loaded with 5-Fu: A Multifunctional drug Delivery System.

In the present work, a simple and efficient stirring method was used to successfully synthesize a novel multifunctional carbon dots-drug delivery system AMP-CDs@5-Fu in the form of intertwined filaments. The results showed that AMP-CDs@5-Fu had the highest final release in the medium mimicking the physiological environment of the human small intestine compared to that of 5-Fu and that the drug release behaviors followed a zero-grade drug release within the first 3h. The results also showed that AMP-CDs@5-Fu could be used to reduce the toxicity of 5-Fu while significantly improving the anticancer ability. In vitro hemolysis and anticancer assays showed that AMP-CDs@5-Fu could significantly improve the anticancer ability while decreasing the toxicity of 5-Fu, and the hemolysis rate of AMP-CDs@5-Fu was significantly lower than that of 5-Fu; their IC50 against 4T1 cancer cells were 201.63 ± 8.94µg 5-Fu/mL and 241.24 ± 11.05µg 5- Fu/mL. In addition, AMP-CDs@5-Fu allowed clear cell imaging. Therefore, AMP-CDs@5-Fu is expected to improve the bioavailability of 5-Fu as a novel oral agent with fluorescent properties and very promising as a novel fluorescence tracking drug loading system, which is expected to be used in the field of anticancer targeted therapy and fluorescence tracking to monitor the distribution of drugs.

Advanced applications of DNA nanostructures dominated by DNA origami in antitumor drug delivery.

DNA origami is a cutting-edge DNA self-assembly technique that neatly folds DNA strands and creates specific structures based on the complementary base pairing principle. These innovative DNA origami nanostructures provide numerous benefits, including lower biotoxicity, increased stability, and superior adaptability, making them an excellent choice for transporting anti-tumor agents. Furthermore, they can considerably reduce side effects and improve therapy success by offering precise, targeted, and multifunctional drug delivery system. This comprehensive review looks into the principles and design strategies of DNA origami, providing valuable insights into this technology's latest research achievements and development trends in the field of anti-tumor drug delivery. Additionally, we review the key function and major benefits of DNA origami in cancer treatment, some of these approaches also involve aspects related to DNA tetrahedra, aiming to provide novel ideas and effective solutions to address drug delivery challenges in cancer therapy.

An injectable MB/BG@LG sustained release lipid gel with antibacterial and osteogenic properties for efficient treatment of chronic periodontitis in rats

Periodontitis is a chronic inflammatory disease characterized by the colonization of pathogenic microorganisms and the loss of periodontal supporting tissue. However, the existing local drug delivery system for periodontitis has some problems including subpar antibacterial impact, easy loss, and unsatisfactory periodontal regeneration. In this study, a multi-functional and sustained release drug delivery system (MB/[email protected]) was developed by encapsulating methylene blue (MB) and bioactive glass (BG) into the lipid gel (LG) precursor by Macrosol technology. The properties of MB/[email protected] were characterized using a scanning electron microscope, a dynamic shear rotation rheometer, and a release curve. The results showed that MB/[email protected] could not only sustained release for 16 days, but also quickly fill the irregular bone defect caused by periodontitis through in situ hydration. Under 660 ​nm light irradiation, methylene blue-produced reactive oxygen species (ROS) can reduce local inflammatory response by inhibiting bacterial growth. In addition, in vitro and vivo experiments have shown that MB/[email protected] can effectively promote periodontal tissue regeneration by reducing inflammatory response, promoting cell proliferation and osteogenic differentiation. In summary, MB/[email protected] exhibited excellent adhesion properties, self-assembly properties, and superior drug release control capabilities, which improved the clinical feasibility of its application in complex oral environments.

PH-responsive materials based on sodium carboxymethyl cellulose as a safe and effective strategy for camptothecin delivery

The safe and efficient delivery of drugs is regarded as a fundamental strategy for enhancing the low effectiveness of cancer treatments. Herein, a simple preparation approach for a multifunctional drug delivery system was reported. The novel structure of spiropyran (SP), 1-(6 ´-bromo-hexyl)−3,3-dimethyl indoline-6 ´ -methoxy benzopyran, was used to modify sodium carboxymethyl cellulose (NaCMC) for controlling drug release. SP has a heightened sensitivity to variations in pH, with a linear response range of .2–5.5. The elevated drug loading (31.68 %) can be attributed to the hydrophobic interaction of SP and the adsorption of NaCMC. Porous materials composed of zinc ions and dimethylimidazole (ZIF-8) as an embedded shell, which serves as a barrier that effectively reduces drug leakage from 20 % to 12 %, thus mitigating the side effects of camptothecin (CPT) in alkaline conditions. In acidic conditions, the collapse of ZIF-8 provides zinc ions that act as crosslinking agents for NaCMC, thereby improving the channel of drug release and enhancing the release amount from 51.9 % to 66.7 % compared with SP-grafted NaCMC micelles. The inherent biological adhesion of NaCMC ensures sustained drug release for a period of up to 40 h. These pH-responsive carriers hold great promise in the safe and effective treatment of cancer in the gastrointestinal tract, with CPT emerging as a highly promising candidate.

The design and straightforward synthesis of multifunctional DNA microgels for the improved targeted delivery of antitumor drugs

Multifunctional drug delivery platforms represent ideal approaches to reliably targeting pharmacological agents of interest to the complex tumor microenvironment (TME), yet the complicated synthesis processes, high costs, and toxicities associated with these agents have hindered their clinical application to date. In this study, the properties of the TME are leveraged to develop a multifunctional pNAB/AS DNA microgel that is able to actively target tumors. This microgel is generated by a straightforward one-step free radical precipitation polymerization procedure, exhibiting extremely high drug encapsulation efficiency (∼90%), and is responsive to three environmental stimuli including temperature, reduction, and an acidic pH while showing minimal drug leakage under physiological conditions. Through a synergistic combination of appropriate size and aptamer recognition, this microgel is able to reliably facilitate intratumoral drug accumulation and nuclear drug delivery. Critically, pNAB/AS-Dox treatment is associated with specific antitumor activity in vitro and in vivo while retaining a good biosafety profile and causing lower levels of off-target toxicity as compared to free drug treatment. Together, these findings emphasize the potential value of this multifunctional pNAB/AS DNA microgel as a platform amenable to targeted drug delivery to the TME, providing a foundation for further efforts to readily develop multifunctional drug delivery systems.

Preparation of Selenium-Based Drug-Modified Polymeric Ligand-Functionalised Fe3O4 Nanoparticles as Multimodal Drug Carrier and Magnetic Hyperthermia Inductor.

In recent years, much effort has been invested into developing multifunctional drug delivery systems to overcome the drawbacks of conventional carriers. Magnetic nanoparticles are not generally used as carriers but can be functionalised with several different biomolecules and their size can be tailored to present a hyperthermia response, allowing for the design of multifunctional systems which can be active in therapies. In this work, we have designed a drug carrier nanosystem based on Fe3O4 nanoparticles with large heating power and 4-amino-2-pentylselenoquinazoline as an attached drug that exhibits oxidative properties and high selectivity against a variety of cancer malignant cells. For this propose, two samples composed of homogeneous Fe3O4 nanoparticles (NPs) with different sizes, shapes, and magnetic properties have been synthesised and characterised. The surface modification of the prepared Fe3O4 nanoparticles has been developed using copolymers composed of poly(ethylene-alt-maleic anhydride), dodecylamine, polyethylene glycol and the drug 4-amino-2-pentylselenoquinazoline. The obtained nanosystems were properly characterised. Their in vitro efficacy in colon cancer cells and as magnetic hyperthermia inductors was analysed, thereby leaving the door open for their potential application as multimodal agents.

Highly effective corneal permeability of reactive oxygen species-responsive nano-formulation encapsulated cyclosporine a for dry eye management

Dry eye disease (DED) has become a globally recognized public health problem with complex pathogenesis. Recent studies showed that oxidative stress damage and its induced inflammation are the main contributors to the occurrence and progression of dry eye. Here, a novel antioxidative and reactive oxygen species (ROS)-responsive micellar system is reported to improve the ocular surface delivery of highly hydrophobic immunosuppressive cyclosporine A (CSA). This drug carrier is utilized together with the loaded anti-inflammatory drug to achieve a combinatorial treatment of DED. In detail, the selenium substituted random copolymer Se-PEG-PPG is the key to such design, which self-assembles into cornea-penetrating nanoscale micelles with a neutral shell and small size (<50 nm). The Se-PEG-PPG micelles also exerted synergetic therapeutic effects by decreasing intracellular oxidative stress and inhibiting cell apoptosis because of the ROS-scavenging selenium ether group. Finally, the combinatorial anti-oxidation, anti-inflammation, and therapeutic effects of CSA@Se-PEG-PPG eye drops were demonstrated in a murine dry eye model. Taken together, this multifunctional drug delivery system provides a promising approach for the treatment of DED and various ROS-related ocular diseases.