Release Of Dexamethasone Research Articles

Exploring the potential of imidazolium methacrylate crosslinking with resorcinol dimethacrylate for drug delivery systems

AbstractDrug implants offer an alternative for controlling drug release and maintaining plasma levels of a specific drug. In this study, we explored the potential of imidazolium methacrylate crosslinking with resorcinol methacrylate to develop implantable drug delivery systems. The focus was on fabricating a photopolymerizable material based on a novel biocompatible hydrogel for implantable drug delivery systems with dexamethasone, a widely used corticosteroid with potent anti‐inflammatory properties, chosen as the model drug. The experimental section detailed the synthesis of polymerizable units, resin preparation, and resin choice for further tests using a 23 factorial design, printing conditions, material characterization, biocompatibility, and dexamethasone release tests. Our findings shed light on the potential of this novel approach for creating targeted drug delivery systems, holding promise for improving therapeutic outcomes, and reducing side effects associated with systemic long‐term drug administration.

Locally released dexamethasone and its effects on osteogenic activity at implant-tissue interface.

The osseointegration of titanium implants within the host tissue holds crucial importance. The introduction of functional coatings at tissue-implant interface enhances the bioactivity of titanium implants, improves their therapeutic outcomes, and enhances the effectiveness of treatments. In this study, we focused on enhancing the bioactivity of titanium-based implant materials by coating the titanium surfaces with chitosan microspheres, which are loaded with osseointegration-promoting agent dexamethasone (DEX). Initially, chitosan microspheres were successfully produced, followed by DEX loading through diffusion, resulting in a drug loading efficiency of around 50.2 (wt %). The subsequent drug release profile displayed a 24-hour duration, releasing approximately 32.6 (wt %) of the loaded DEX. In cell proliferation assays using human osteosarcoma (SAOS-2) cells, Ti surfaces coated with DEX-loaded chitosan microspheres initially exhibited lower cell numbers compared with DEX-free ones. This observation was attributed to transient osteogenic differentiation effects of DEX, since a notable increase in cell proliferation was observed on the 7th day. Von Kossa staining revealed mineralization beginning on the 14th day, particularly evident in DEX-loaded samples. Moreover, alkaline phosphatase (ALP) activity displayed a pattern of initial increase and subsequent decrease, with DEX release from chitosan microspheres showing a clear influence on the osteogenic differentiation, especially on the 7th day. These findings align with literature, highlighting DEX's potential to enhance osteogenic differentiation and cellular behavior on chitosan microsphere-coated titanium surfaces. This study emphasizes the promising implications for functionalizing surfaces of implant materials with DEX-loaded chitosan microspheres to improve their biocompatibility and bioactivity.

Dual-functional core–shell microneedle patches for oral ulcers treatment

Microneedle patches have been widely used in transdermal drug delivery due to their painless and enhanced drug delivery. Despite their established success, their application within the oral cavity, characterized by a dense distribution of nociceptor, remains largely unexplored. Here, we introduce a well-designed dual-functional core–shell microneedle patches to address oral ulcers. The outer shell of the microneedle tips is crafted from hyaluronic acid (HA) and loaded with lidocaine, while the inner core, composed of gelatin methyl methacrylate (GelMA) encapsulates dexamethasone. The HA shell rapidly dissolves upon application, facilitating the immediate release of lidocaine to induce anesthesia at the ulcer site, thereby alleviating the associated painful sensations. Simultaneously, GelMA imparts mechanical strength and ensured the sustained release of dexamethasone. In vivo experiments further demonstrated that the Dex@MN group exhibiting the most rapid healing rate also displayed the highest levels of collagen deposition and the lowest concentrations of inflammatory factors. This collective evidence underscores the considerable potential of dual-functional core–shell microneedle patches in the treatment of oral diseases.

Inflammation-responsive PCL/gelatin microfiber scaffold with sustained nitric oxide generation and heparin release for blood-contacting implants

Delayed endothelialization, the excessive proliferation of smooth muscle cells (SMCs), and persistent inflammation are the main reasons for the implantation failure of blood-contacting materials. To overcome this problem, an inflammation-responsive, core-shell structured microfiber scaffold is developed using polycaprolactone (PCL), selenocystamine-modified gelatin (Gel-Se), L-ascorbyl 6-palmitate (AP), and dexamethasone as the fiber shell, with poly (l-lysine) (PLL) and heparin incorporated in the fiber core. Superhydrophilic microfiber scaffolds exhibit antifouling properties that inhibit protein adsorption and blood cell adhesion, thereby effectively mitigating the risk of acute thrombosis. The continuous release of heparin and sustained generation of nitric oxide (NO) through the catalytic decomposition of S-nitrosothiols by selenocystamine lead to a biomimetic endothelial function for the enhancement of blood compatibility. The inflammation-responsive compound AP can detoxify excess reactive oxygen species (ROS) while controlling the release of dexamethasone to reduce chronic inflammation. We demonstrate the ability of microfiber scaffolds to reduce thrombotic and inflammatory complications, inhibit SMC proliferation, and promote rapid endothelialization both in vitro and ex vivo. Hence, microfiber scaffolds are robust and promising for blood-contacting implants with enhanced antithrombogenicity and anti-inflammatory capabilities.

Microtubular and high porosity design of electrospun PEGylated poly (lactic-co-glycolic acid) fibrous implant for ocular multi-route administration and medication

Electrospun fibers have been gaining popularity in ocular drug delivery and cellular therapies. However, most of electrospun fibers are planar-shape membrane with large dimension relative to intraocular space, making difficult to use as therapeutic implants. Herein, fibrous microtubes with a hollow center were fabricated by electrospinning using linear diblock mPEG2000-PLGA. Uniform microfibers with 0.809 μm diameter was tailored using Box-Behnken Design model for electrospinning process optimization. The microtubes were 1 mm long with a 0.386 mm diameter. Their suitability for intraocular administration was demonstrated by both injection via a 22-gauge needle and implant via integration of intraocular lens into the vitreous or anterior chamber of eyes, respectively. Electrospun mPEG2000-PLGA had higher porosity, smaller specific surface area, and smaller water contact angle, than that of PLGA. Macroscopically, mPEG2000-PLGA microfibers can maintain overall geometry upon exposure to aqueous buffer for 12 h while having high water uptake and exhibited good elasticity. Hydrolysis with 90 % polymeric degradation in 10.5 weeks underlied sustained slow release of anti-inflammatory drug dexamethasone. PEGylation of PLGA imparted preferential cell adhesion with markedly higher growth of human retinal epithelial cells than lens epithelial ones. This study highlights the potential utility of implantable electrospun PLGA-based microtubes for multiple intraocular delivery routes.

Control of encapsulation efficiency and morphology of poly(lactide-co-glycolide) microparticles with a diafiltration-driven solvent extraction process

The removal of organic solvents during the preparation of biodegradable poly(D,L-lactide-co-glycolide) (PLGA) microparticles by an O/W- solvent extraction/evaporation process was investigated and controlled by diafiltration. Emulsification and steady replacement of the aqueous phase were performed in parallel in a single-vessel setup. During the process, the solidification of the dispersed phase (drug:PLGA:solvent droplets) into microparticles was monitored with video-microscopy and focused beam reflectance measurement (FBRM) and the residual solvent content was analyzed with headspace gas chromatography (organic solvent) and coulometric Karl-Fischer titration (water). Microparticles containing dexamethasone or risperidone were characterized with regard to particle size, morphology, encapsulation efficiency and in-vitro release. Diafiltration-accelerated solvent extraction shortened the process time by accelerating solidification of dispersed phase but reduced the residual dichloromethane content only in combination with increased temperature. Increasing the diafiltration rate increased particle size, porosity, and the encapsulation efficiency of risperidone. The latter effect was particularly evident with increasing lipophilicity of PLGA. A slower and more uniform solidification of end-capped and increased lactide content PLGA grade was identified as the reason for an increased drug leaching. Accelerated solvent extraction by diafiltration did not affect the in-vitro release of risperidone from different PLGA grades. The initial burst release of dexamethasone was increased by diafiltration when encapsulated in concentrations above the percolation threshold. Both porosity and burst release could be reduced by increasing the process temperature during diafiltration. Residual water content was established as an indicator for porosity and correlated with the burst release of dexamethasone.

Accelerated removal of solvent residuals from PLGA microparticles by alcohol vapor-assisted fluidized bed drying

The removal of residual solvents from biodegradable poly(D,L-lactide-co-glycolide) (PLGA) microparticles by fluidized bed drying was investigated. Microparticles were prepared by the O/W solvent extraction/evaporation method and the influence of various process and formulation parameters on the secondary drying was studied. PLGA microparticles and films were characterized for residual organic solvent and water content, recrystallisation, surface morphology, drug loading and in-vitro release of the drugs dexamethasone and risperidone. While alcohol-free fluidized bed drying decreased the residual dichloromethane content only from about 7 % (w/w) to 6.4 % (w/w) (18 °C) or 3.2 % (w/w) (35 °C) within 24 h, 140 mg/L methanol vapor in purge gas facilitated almost complete removal of dichloromethane or ethyl acetate from microparticles (0–0.11 % (w/w) after 6 h). By controlling the alcohol concentration and temperature of the purge gas, the alcohol absorption and complete removal was controlled. Risperidone increased the methanol absorption enhancing the plasticization. A high initial residual water content was identified to promote aggregation and was eliminated by starting fluidized bed drying without alcohol. Alcohol vapor-assisted fluidized bed drying accelerated microparticle manufacturing without affecting the redispersibility, the drug loading and the in-vitro release of risperidone and dexamethasone.

Reactive Oxygen Species Triggered Cleavage of Thioketal‐Containing Supramolecular Nanoparticles for Inflammation‐Targeted Oral Therapy in Ulcerative Colitis

AbstractCombating reactive oxygen species (ROS) and targeted drug delivery to inflammatory sites are considered effective therapeutic strategies for ulcerative colitis (UC), a refractory chronic inflammatory disease. Herein, a ROS‐responsive thioketal (TK) crosslinked cyclodextrin metal‐organic framework (TCOF) is fabricated, to which a non‐ROS‐sensitive vector, sulfur substituted by carbon chain‐crosslinked cyclodextrin metal‐organic framework (CCOF) is parallelly designed as ROS negative reference. Dexamethasone (DEX) loaded in TCOF (TCD) and CCOF (CCD) are investigated to demonstrate the advantages of precision medicine for UC. After the ROS‐induced collapse of nanoparticles, TCD selectively triggered the release of DEX. Moreover, TCD effectively protected cells from oxidative stress damage and reduced inflammation levels in vitro. Remarkably, the TK group of TCD is oxidatively broken by consuming ROS at the inflammatory site, exposing the thiol group to mucosal adhesion, which enhances the retention of TCD at colons. In vivo studies of UC treatment reveals that oral administration of TCD demonstrated excellent inflammation‐targeting properties, remarkably attenuated oxidative stress, and ameliorated both acute and chronic colitis compared to CCD. Furthermore, TCD exhibits an excellent safety profile in mice. These results instill confidence in advancing targeted drug delivery and precision therapy for UC.

Dexamethasone-loaded ROS stimuli-responsive nanogels for topical ocular therapy of corneal neovascularization

Dexamethasone (DEX) has been demonstrated to inhibit the inflammatory corneal neovascularization (CNV). However, the therapeutic efficacy of DEX is limited by the poor bioavailability of conventional eye drops and the increased risk of hormonal glaucoma and cataract associated with prolonged and frequent usage. To address these limitations, we have developed a novel DEX-loaded, reactive oxygen species (ROS)-responsive, controlled-release nanogel, termed DEX@INHANGs. This advanced nanogel system is constructed by the formation of supramolecular host-guest complexes by cyclodextrin (CD) and adamantane (ADA) as a cross-linking force. The introduction of the ROS-responsive material, thioketal (TK), ensures the controlled release of DEX in response to oxidative stress, a characteristic of CNV. Furthermore, the nanogel's prolonged retention on the corneal surface for over 8 h is achieved through covalent binding of the integrin β1 fusion protein, which enhances its bioavailability. Cytotoxicity assays demonstrated that DEX@INHANGs was not notably toxic to human corneal epithelial cells (HCECs). Furthermore, DEX@INHANGs has been demonstrated to effectively inhibit angiogenesis in vitro. In a rabbit model with chemically burned eyes, the once-daily topical application of DEX@INHANGs was observed to effectively suppress CNV. These results collectively indicate that the nanomedicine formulation of DEX@INHANGs may offer a promising treatment option for CNV, offering significant advantages such as reduced dosing frequency and enhanced patient compliance.

Wearable dual-drug controlled release patch for psoriasis treatment

Wearable drug delivery systems (DDS) have made significant advancements in the field of precision medicine, offering precise regulation of drug dosage, location, and timing. The performance qualities that wearable DDS has always strived for are simplicity, efficiency, and intelligence. This paper proposes a wearable dual-drug synergistic release patch. The patch is powered by a built-in magnesium battery and utilizes a hydrogel containing viologen-based hyperbranched polyamidoamine as both a cathode material and an integrated drug reservoir. This design allows for the simultaneous release of both dexamethasone and tannic acid, overcoming the limitations of monotherapy and ensuring effective synergy for on-demand therapy. In a mouse model with praziquimod-induced psoriasis, the patch demonstrated therapeutic efficacy at a low voltage. The inflammatory skin returned to normal after 5 days with the on-demand release of dual drugs. This work provides a promising treatment option considering its straightforward construction and the therapeutic advantages of dual-drug synergy.

Investigating the in-vitro bioactivity, biodegradability and drug release behavior of the newly developed PES/HA/WS biocompatible nanocomposites as bone graft substitute

The nucleation of carbonate-containing apatite on the biomaterials surface is regarded as a significant stage in bone healing process. In this regard, composites contained hydroxyapatite (Ca10(PO4)6(OH)2, HA), wollastonite (CaSiO3, WS) and polyethersulfone (PES) were synthesized via a simple solvent casting technique. The in-vitro bioactivity of the prepared composite films with different weight ratios of HA and WS was studied by placing the samples in the simulated body fluid (SBF) for 21 days. The results indicated that the the surface of composites containing 2 wt% HA and 4 wt% WS was completely covered by a thick bone-like apatite layer, which was characterized by Grazing incidence X-ray diffraction, attenuated total reflectance–Fourier transform infrared spectrometer, field emission electron microscopy and energy dispersive X-ray analyzer (EDX). The degradation study of the samples showed that the concentration of inorganic particles could not influence the degradability of the polymeric matrix, where all samples expressed similar dexamethasone (DEX) release behavior. Moreover, the in-vitro cytotoxicity results indicated the significant cyto-compatibility of all specimens. Therefore, these findings revealed that the prepared composite films composed of PES, HA, WS and DEX could be regarded as promising bioactive candidates with low degradation rate for bone tissue engineering applications.

Remote-controlled dexamethasone-duration on eye-surface with a micelle-magnetic nanoparticulate co-delivery system for dry eye disease

Dexamethasone (DEX) is used to treat ocular surface diseases. However, regulating DEX duration in tears while preventing its absorption into the anterior chamber is critical for balancing its therapy effects and the side effects. In this study, a novel magnetic nanoparticle (MNP)-micelle (MC) co-delivery system (MMDS) was developed. The MC moiety in the MMDS served as the carrier for DEX and the MNP part endowed the MMDS with magnetic-responsive properties. To extend its residency, the MMDS was magnetically attracted by an external magnet after instilling, which acted as a precorneal drug-depot enabling a sustainable release of DEX in tears. With combination of magnet treatment, the topical instillation of MMDS@DEX significantly prolonged the DEX-retention in tears and increased the DEX-concentration in the cornea and conjunctiva, as well as concurrently reduced the DEX-level in the aqueous humor, when compared with the commercial DEX eye drop treatment. The combination of MMDS@DEX and magnet treatment exerted significantly better therapeutic effects against DED with smaller side effects than conventional treatments including DEX suspension, commercial DEX eye drops, as well as the MMDS@DEX treatment alone. The present work provided a new method for the effective delivery of DEX to ocular surface tissues while reducing its side effects, which will be beneficial to the treatments of a wide range of ocular surface diseases.

Lacrimal occlusion and anti-inflammation with dexamethasone microcrystals incorporated gelatin methacryloyl-based plugs for treatment of dry eye

Dry eye, a frequently encountered disease of the ophthalmic clinic, is characterized by tear deficiency and ocular surface inflammation. Tear preservation through lacrimal drainage system plugs and anti-inflammatory therapy with glucocorticoids are generally used separately to control the disease progression. However, inherent limitations of current available plugs have necessitated the pursuit of new materials for plug production. Meanwhile, the therapeutic effects of glucocorticoids have been compromised by frequent dosing which reduces patient compliance. To address this, our present study developed a dexamethasone eluting intracanalicular plug (DEX-Plug) with dexamethasone microcrystals (DEX MCs) and gelatin methacryloyl (GelMA), which treated dry eye by simultaneous lacrimal occlusion and anti-inflammation. The resultant plug was biodegradable, biocompatible, and swelled rapidly to adapt the irregular anatomical structure of lacrimal canaliculi. It can block the lacrimal drainage system while serving as a drug delivery vehicle for sustained release of dexamethasone. The dual-functional therapeutic effects of DEX-Plug were demonstrated in a rabbit dry eye model using lissamine green drainage rates, the Schirmer’s test, corneal fluorescein staining, and real-time PCR. The plug reported herein can also be harnessed to deliver drugs other than dexamethasone, thus providing a novel approach to improve the treatment of dry eye.

Sustained zero-order release of dexamethasone after incorporation into crosslinked PEG-dendrons using click reactions

Hydrogel-based localised drug delivery minimises systemic side effects and a linear release profile ensuring a sustained drug release over time, crucial for long-term therapy. The current paper describes the use of the Copper(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAc) to append azidified Dexamethasone (Dex) onto dendrons of first- and second-generation PEGs. Crosslinking with thiolated PEGs using either thiol-acrylate or nucleophilic addition reactions yielded gels containing β-thio-ether ester groups that imparted enhanced hydrolytic susceptibility. In vitro gel degradation was followed gravimetrically and expressed as swelling ratios. Thiol-acrylate crosslinked hydrogels exhibited zero-order Dex release kinetics over 11, 27, and 16 days (G1, G1-star, and G2). Crosslinking the G1-gels by nucleophilic addition also resulted in linear release and the end point was reached in 5 days. Hydrolysis was accounted as the main release mechanism for covalently bound Dex, while physically incorporated Dex showed undefined rapid burst or first-order release, with most of the drug released in the initial 1–3 days. Eluates from covalently bound Dex maintained high activity, whereas Trap-Dex gels lost activity over time, as detected by the upregulation of luciferase expression from a transformed cell line. This novel chemistry combination offers precise drug release control applicable beyond Dex to drugs with suitable nucleophilic groups.

Intravitreal OZURDEX vs. Intravitreal Bevacizumab for Diabetic Macular Edema: A Comprehensive Review.

This comprehensive review examines the efficacy, safety, and implications of intravitreal OZURDEX and intravitreal bevacizumab in treating diabetic macular edema (DME). DME is a common complication of diabetes mellitus and a leading cause of vision loss. OZURDEX, through sustained release of dexamethasone, targets inflammation and vascular permeability, while bevacizumab inhibits vascular endothelial growth factor (VEGF), reducing angiogenesis. However, differences in safety profiles exist, with OZURDEX associated with an increased risk of intraocular pressure elevation and cataract formation and bevacizumab potentially carrying systemic risks. The choice between these treatments should be individualized, considering patient preferences, ocular and systemic comorbidities, and cost-effectiveness. Collaboration among healthcare providers is essential for the comprehensive management of DME. Future research should focus on long-term comparative studies, predictors of treatment response, and exploration of novel therapeutic targets to optimize treatment outcomes for patients with DME.

A sericin hydrogel scaffold for sustained dexamethasone release modulates macrophage polarization to promote mandibular bone defect repair in rats

To evaluate the efficacy of a modified sericin hydrogel scaffold loaded with dexamethasone (SMH-CD/DEX) scaffold for promoting bone defect healing by stimulating anti-inflammatory macrophage polarization. The light-curable SMH-CD/DEX scaffold was prepared using dexamethasone-loaded NH2-β-cyclodextrin (NH2-β-CD) and sericin hydrogel and characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), biocompatibility assessment and drug release test. THP-1 macrophages incubated with the scaffold were examined for protein expressions of iNOS and Arg-1, mRNA expressions of IL-6, Il-10, Arg-1 and iNOS, and surface markers CD86 and CD206 using Western blotting, RT-qPCR, and flow cytometry. In a co-culture system of human periodontal ligament stem cells (HPDLSCs) and THP-1 macrophages, the osteogenic ability of the stem cells incubated with the scaffold was evaluated by detecting protein expressions of COL1A1 and Runx2 and expressions of ALP, Runx2, OCN and BMP2 mRNA, ALP staining, and alizarin red staining. In a rat model of mandibular bone defect, the osteogenic effect of the scaffold was assessed by observing bone regeneration using micro-CT and histopathological staining. In THP-1 macrophages, incubation with SMH-CD/DEX scaffold significantly enhanced protein expressions of Arg-1 and mRNA expressions of IL-10 and Arg-1 and lowered iNOS protein expression and IL-6 and iNOS mRNA expressions. In the co-culture system, SMH-CD/DEX effectively increased the protein expressions of COL1A1 and Runx2 and mRNA expressions of ALP and BMP2 in HPDLSCs and promoted their osteogenic differentiation. In the rat models, implantation of SMH-CD/DEX scaffold significantly promoted bone repair and bone regeneration in the bone defect. The SMH-CD/DEX scaffold capable of sustained dexamethasone release promotes osteogenic differentiation of stem cells and bone defect repair in rats by regulating M2 polarization.

Dexamethasone nanomedicines with optimized drug release kinetics tailored for treatment of site-specific rheumatic musculoskeletal diseases

The application of polymer-based drug delivery systems is advantageous for improved pharmacokinetics, controlled drug release, and decreased side effects of therapeutics for inflammatory disease. Herein, we describe the synthesis and characterization of linear N-(2-hydroxypropyl)methacrylamide-based polymer conjugates designed for controlled release of the anti-inflammatory drug dexamethasone through pH-sensitive bonds. The tailored release rates were achieved by modifying DEX with four oxo-acids introducing reactive oxo groups to the DEX derivatives. Refinement of reaction conditions yielded four well-defined polymer conjugates with varied release profiles which were more pronounced at the lower pH in cell lysosomes. In vitro evaluations in murine peritoneal macrophages, human synovial fibroblasts, and human peripheral blood mononuclear cells demonstrated that neither drug derivatization nor polymer conjugation affected cytotoxicity or anti-inflammatory properties. Subsequent in vivo tests using a murine arthritis model validated the superior anti-inflammatory efficacy of the prepared DEX-bearing conjugates with lower release rates. These nanomedicines showed much higher therapeutic activity compared to the faster release systems or DEX itself.

Nanoengineered oxygen-releasing polymeric scaffold with sustained release of dexamethasone for bone regeneration

Maintaining the continuous oxygen supply and proper cell growth before blood vessel ingrowth at the bone defect site are considerably significant issues in bone regeneration. Oxygen-producing scaffolds can supply oxygen and avoid hypoxia leading to expedited bone regeneration. Herein, first oxygen-producing calcium peroxide nanoparticles (CPO NPs) are synthesized, and subsequently, the various amounts of synthesized CPO NPs (0.1, 0.5, and 1 wt/v%) loaded in the scaffold composite, which is developed by simple physical blending of chitosan (CS) and polycaprolactone (PCL) polymers. To deliver the synergistic therapeutic effect, dexamethasone (DEX), known for its potential anti-inflammatory and osteogenic properties, is loaded into the nanocomposite scaffolds. The extensive physicochemical characterizations of nanocomposite scaffolds confirm the successful loading of CPO NPs, adequate porous morphology, pore size, hydrophilicity, and biodegradability. In vitro, biological studies support the antibacterial, hemocompatible, and cytocompatible (MG-63 and MC3T3-E1 cells) nature of the material when tested on respective cells. Field emission scanning electron microscopy and energy-dispersive x-ray spectroscopy confirm the successful biomineralization of the scaffolds. Scaffolds also exhibit the sustained release of DEX and efficient protein adsorption. This study revealed that a nanoengineered scaffold loaded with CPO NPs (PCL/CS/DEX/CPO 3) is a suitable candidate for bone tissue regeneration.

Anti-fibrotic and anti-stricture effects of biodegradable biliary stents braided with dexamethasone-impregnated sheath/core structured monofilaments

Endoscopic biliary stent insertion has been widely used for the treatment of benign biliary stricture (BBS). Thus, the development of stent materials in the perspectives of structure, mechanical properties, and biocompatibility has been also studied. However, conventional metal and plastic stents have several disadvantages, such as repeated procedures to remove or exchange them, dislodgment, restenosis, biocompatibility, and poor mechanical properties. Sustainable effectiveness, attenuation and prevention of fibrosis, and biocompatibility are key factors for the clinical application of stents to BBS treatment. In addition, loading drugs could show synergistic effects with stents’ own performance. We developed a dexamethasone-eluting biodegradable stent (DBS) consisting of a sheath/core structure with outstanding mechanical properties and sustained release of dexamethasone, which maintained its functions in a BBS duct over 12 weeks in a swine model. The insertion of our DBS not only expanded BBS areas but also healed secondary ulcers as a result of the attenuation of fibrosis. After 16 weeks from the insertion, BBS areas were totally improved, and the DBS was degraded and thoroughly disappeared without re-intervention for stent removal. Our DBS would be an effective clinical tool for non-vascular diseases. Statement of significanceThis study describes the insertion of a drug-eluting biodegradable stent (DBS) into the bile duct. The sheath/core structure of DBS confers substantial durability and a sustained drug release profile. Drug released from the DBS exhibited anti-fibrotic effects without inflammatory responses in both in vitro and in vivo experiments. The DBS maintained its function over 12 weeks after insertion into the common bile duct, expanding benign biliary stricture (BBS) and reducing inflammation to heal secondary ulcers in a swine BBS model. After 16 weeks from the DBS insertion, the DBS thoroughly disappeared without re-intervention for stent removal, resulting in totally improved BBS areas. Our findings not only spotlight the understanding of the sheath/core structure of the biodegradable stent, but also pave the way for the further application for non-vascular diseases.

Ameliorated Skin Inflammation through the Synergistic Effect of Gold Nanorod-Dexamethasone and Photothermal Therapy.

Psoriasis, a prevalent chronic inflammatory skin ailment affecting approximately 2-3% of the global population, is characterized by persistent symptoms. Dexamethasone, a primary corticosteroid for treating psoriasis, demonstrates notable efficacy; however, its limited skin permeation results in documented adverse effects. To address this, the presented study employed a novel strategy to conjugate gold nanorod and dexamethasone and evaluate their potential for mitigating psoriatic inflammation using an imiquimod-induced mouse model and human skin cells. Our findings revealed enhanced cutaneous penetration of gold nanorod and dexamethasone conjugates compared with that of dexamethasone, owing to superior skin penetration. Gold nanorod and dexamethasone conjugates demonstrated an optimal pharmacological impact at minimal dosages without toxicity during extended use. To further enhance the effectiveness of gold nanorod and dexamethasone conjugates, 808 nm near-infrared laser irradiation, which reacts to gold, was additionally applied to achieve thermal elevation to expedite drug skin penetration. Supplementary laser irradiation at 808 nm significantly ameliorated psoriatic symptoms following deep gold nanorod and dexamethasone conjugates penetration. This corresponded with restored peroxisome proliferator-activated receptor-γ levels and accelerated dexamethasone release from the gold nanorod and dexamethasone conjugates complex. These findings highlight the potential of gold nanorod and dexamethasone conjugates to enhance drug penetration through dermal layers, thereby aiding psoriasis treatment. Moreover, its compatibility with photothermal therapy offers prospects for novel therapeutic interventions across various inflammatory skin disorders.