Novel Thermosensitive and Mucoadhesive Nasal Hydrogel Containing 5-MeO-DMT Optimized Using Box-Behnken Experimental Design.

We present the development and characterization of a nasal drug delivery system comprised of a thermosensitive mucoadhesive hydrogel based on a mixture of the polymers Poloxamer 407, Poloxamer 188 and Hydroxypropyl-methylcellulose, and the psychedelic drug 5-methoxy-N,-N-dimethyltryptamine. The development relied on a 3 × 3 Box-Behnken experimental design, focusing on optimizing gelification temperature, viscosity and mucoadhesion. The primary objective of this work was to tailor the formulation for efficient nasal drug delivery. This would increase contact time between the hydrogel and the mucosa while preserving normal ciliary functioning. Following optimization, the final formulation underwent characterization through an examination of the in vitro drug release profile via dialysis under sink conditions. Additionally, homogeneity of its composition was assessed using Raman Confocal Spectroscopy. The results demonstrate complete mixing of drug and polymers within the hydrogel matrix. Furthermore, the formulation exhibits sustained release profile, with 73.76% of the drug being delivered after 5 h in vitro. This will enable future studies to assess the possibility of using this formulation to treat certain mental disorders. We have successfully developed a promising thermosensitive and mucoadhesive hydrogel with a gelling temperature of around 32 °C, a viscosity close to 100 mPas and a mucoadhesion of nearly 4.20 N·m.

Gelatin-based nanoparticles and antibiotics: a new therapeutic approach for osteomyelitis?

The result of infection of bone with microorganisms is osteomyelitis and septic arthritis. Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for most of its cases (more than 50%). Since MRSA is resistant to many treatments, it is accompanied by high costs and numerous complications, necessitating more effective new treatments. Recently, development of gelatin nanoparticles have attracted the attention of scientists of biomedicine to itself, and have been utilized as a delivery vehicle for antibiotics because of their biocompatibility, biodegradability, and cost-effectiveness. Promising results have been reported with gelatin modification and combinations with chemical agents. Although these findings have been suggested that gelatin has the potential to be a suitable option for continuous release of antibiotics in osteomyelitis and septic arthritis treatment, they still have not become routine in clinical practices. The most deliver antibiotic using gelatin-derived composites is vancomycin which is showed the good efficacy. To date, a number of pre-clinical studies evaluated the utility of gelatin-based composites in the management of osteomyelitis. Gelatin-based composites were found to have satisfactory performance in the control of infection, as well as the promotion of bone defect repair in chronic osteomyelitis models. This review summarized the available evidence which provides a new insight into gelatin-derived composites with controlled release of antibiotics.

Long-Term Follow-up of Patients With Cytomegalovirus Retinitis Treated With a Ganciclovir Implant.

Purpose: To assess the long-term safety and clinical outcomes of a ganciclovir intravitreal implant in patients with cytomegalovirus (CMV) retinitis. Methods: A retrospective study was performed of patients with CMV retinitis treated with a ganciclovir intravitreal implant. Results: The study included 13 patients (16 eyes) previously treated with a ganciclovir intravitreal implant. The mean time since the last implant placement was 21.3 years and the mean total duration of follow-up, 22.7 years. Visual acuity (VA) ranged from 20/25 to light perception, with 56% of eyes maintaining a VA of 20/60 or better at the most recent follow-up examination. Common ocular complications included epiretinal membrane (38%), macular fibrosis/scarring (25%), retinal detachment (RD) (25%), implant dislocation (25%), and immune reactivation uveitis (19%). Intraocular surgery was required in 10 eyes (63%), with the most frequent being cataract extraction (31%), pars plana vitrectomy (PPV) for implant removal (19%), and PPV for RD (13%). Conclusions: Results show the long-term safety of the ganciclovir intravitreal implant despite its residual inactive inert shell. Complication rates are consistent with those expected from infectious sequelae.

Prolonged Microcystis restraint through allelochemicals sustained-release microspheres regulated by carbon material (CM-AC@SM): Optimal formulation, characterization, effects and synergistic inhibition mechanisms.

The Microcystis blooms have caused serious damage to aquatic ecosystems. Microspheres containing allelochemicals with sustained-release properties have the potential to function as a cost-effective and environmentally friendly algaecide against M. aeruginosa. In the current investigation, we successfully optimized the synthesis of allelochemicals sustained-release microspheres regulated by carbon material (CM-AC@SM), which demonstrated a high embedding rate (90.17 %) and loading rate (0.65 %), with an accumulative release rate of 53.27 % on day 30. To investigate the sustained-release mechanism of CM-AC@SM, the sustained-release process of allelochemicals was determined using the Folin-Phenol method and the immersion behavior of the CM-AC@SM was characterized through SEM and XPS. Results showed that allelochemicals were released in the delayed-dissolution mode. In addition, to elucidate the synergistic mechanism of CM-AC@SM towards the inhibition of M. aeruginosa, this study comprehensively assessed the effects of allelochemicals, carbon material and CM-AC@SM on the morphology, antioxidant system activity and photosynthetic activity of M. aeruginosa. The findings indicated that allelochemicals and carbon material induced intracellular protein and nucleic acid leakage by increasing cell membrane permeability, disrupted the extracellular and intracellular morphology of algae, triggered peroxidative damage and restrained antioxidant system activity by stimulating the generation of reactive oxygen species. Simultaneously, the activity of photosystem II was inhibited by allelochemicals and carbon material, substantiated by the reduction in Fv/Fo and Fv/Fm ratios. Hence, CM-AC@SM shows promise in inhibiting M. aeruginosa, offering an efficient approach for the future large-scale control of harmful algal blooms (HABs).

Scope and Application of Hot Melt Extrusion in the Development of Controlled and Sustained Release Drug Delivery Systems.

Controlled-release drug delivery systems (CRDDS) are more beneficial than conventional immediate release (IRDDS) for reduced intake, prolonged duration of action, lesser adverse effects, higher bioavailability, etc. The preparation of CRDDS is more complex than IRDDS. The hot melt extrusion (HME) technique is used for developing amorphous solid dispersion of poorly water soluble drugs to improve their dissolution rate and oral bioavailability. HME can be employed to develop CRDDS. Sustained release delivery systems (SRDDS), usually given orally, can also be developed using HME. This technique has the advantages of using no organic solvent, converting crystalline drugs to amorphous, improving bioavailability, etc. However, the heat sensitivity of drugs, miscibility between drug-polymer, and the availability of a few polymers are some of the challenges HME faces in developing CRDDS and SRDDS. The selection of a suitable polymer and the optimization of the process with the help of the QbD principle are two important aspects of the successful application of HME. In this review, strategies to prepare SRDDS and CRDDS using HME are discussed with its applications in research.

A Low-Temperature Na-MoS2 Rechargeable Battery.

It is generally accepted that the low-temperature environment typically augments electrolyte viscosity and impedes electrochemical kinetics, thereby diminishing battery performance. However, this prevailing notion, while valid in certain contexts, lacks universality, particularly regarding cycling stability. In this context, the Na-MoS2 batteries serve as a model to elucidate the impacts of low temperatures. By significantly suppressing the pulverization and amorphization of MoS2, the low-temperature milieu effectively mitigates the risk of micro-short circuits induced by the mass shuttling to the Na metal anode, thereby averting performance degradation by self-discharge. Upon cycling, the generated NaxMo3S4 intermediates only at low temperatures benefit the structural and electrochemical stabilizations to counteract the intrinsic performance degradation. The attenuation of kinetics at low temperatures facilitates the accumulation of Na2S, akin to a sustained-release agent within the electrode, steadily furnishing the capacity in long cycling. Moreover, the suppression of polysulfide dissolution and shuttling emerges as a pivotal factor contributing to the cycling stability at low-temperature. These findings provide a rewarding avenue toward understanding of the influence of low temperature on battery performance, as well as the design of practical electrodes and batteries for low-temperature applications.

Sustained-release mechanism of ß-Cyclodextrin/cationic cellulose-stabilized Pickering emulsions loaded with citrus essential oil.

Citrus oil (CO) is a commonly used natural flavor with high volatility, which is not conducive to sustained release under food environmental stress. This study constructed novel ß-cyclodextrin/cationic cellulose nanocrystal (ß-CD/C-CNC) complexes via noncovalent interaction, which were used to stabilize CO-loaded Pickering emulsions (PEß-CD/C-CNC). The C-CNC greatly improved the physical stability, droplet dispersion and viscoelasticity of PEß-CD/C-CNC by forming a tight network structure, as verified by rheological behavior. Moreover, C-CNC improved the wettability of ß-CD/C-CNC complexes and enhanced the interaction between adjacent ß-CD/C-CNC complexes. C-CNC also contributed to the interfacial viscoelasticity, hydrated mass, and layer thickness via the interfacial dilational modulus and QCM-D. ß-CD/C-CNC complexes adsorbed on the oil-water interface gave rise to a dense filling layer as a physical barrier, enhancing the sustained-release performance of PEß-CD/C-CNC by limiting diffusion of citrus essential oil into the headspace. This study provides new technical approaches for aroma retention in the food industry.

Construction and evaluation of liposomal drug delivery system for an ALK/HDACs dual-targeted inhibitor with sustained release and enhanced antitumor effect.

ALK/HDACs dual target inhibitor (PT-54) was a 2,4-pyrimidinediamine derivative synthesized based on the pharmacophore merged strategy that inhibits both anaplastic lymphoma kinase (ALK) and histone deacetylases (HDACs), which has demonstrated significant efficacy in treating multiple cancers. However, its poor solubility in water limited its clinical application. In this study, we prepared PT-54 liposomes (PT-54-LPs) by the membrane hydration method to overcome this defect. The encapsulation efficiency (EE) and particle size were used as evaluation indicators to explore the preparation conditions of PT-54-LPs. The morphology, particle size, EE, drug loading content (DLC), drug release properties, and stability of PT-54-LPs were further investigated. In vitro drug release studies showed that PT-54-LPs exhibited significant slow-release properties compared with free PT-54. PT-54-LPs also showed better tumor inhibitory effects than free PT-54 without significant adverse effects. These results suggested that PT-54-LPs displayed sustained drug release and significantly improved the tumor selectivity of PT-54. Thus, PT-54-LPs showed significant promise in enhancing anticancer efficiency.

Sustained release of 5-aminosalicylic acid from azoreductase-responsive polymeric prodrugs for prolonged colon-targeted colitis therapy.

Ulcerative colitis (UC) is a challenging inflammatory gastrointestinal disorder, whose therapies encounter limitations in overcoming insufficient colonic retention and rapid systemic clearance. In this study, we report an innovative polymeric prodrug nanoformulation for targeted UC treatment through sustained 5-aminosalicylic acid (5-ASA) delivery. Amphiphilic polymer-based 13.5 nm micelles were engineered to incorporate azo-linked 5-ASA prodrug motifs, enabling cleavage via colonic azoreductases. In vitro, micelles exhibited excellent stability under gastric/intestinal conditions while demonstrating controlled 5-ASA release over 24 h in colonic fluids. Orally administered micelles revealed prolonged 24-h retention and a high accumulation within inflamed murine colonic tissue. At an approximately 60% dose reduction from those most advanced recent studies, the platform halted DSS colitis progression and outperformed standard 5-ASA therapy through a 77-97% suppression of inflammatory markers. Histological analysis confirmed intact colon morphology and restored barrier protein expression. This integrated prodrug nanoformulation addresses limitations in colon-targeted UC therapy through localized bioactivation and tailored pharmacokinetics, suggesting the potential of nanotechnology-guided precision delivery to transform disease management.

Antimicrobial, antioxidant and cytocompatible coaxial wet-spun fibers made of polycaprolactone and cellulose acetate loaded with essential oils for wound care.

Chronic wounds represent a serious worldwide concern, being often associated with bacterial infections. As the prevalence of bacterial infections increase, it is crucial to search for alternatives. Essential oils (EOs) constitute a promising option to antibiotics due to their strong anti-inflammatory, analgesic, antioxidant and antibacterial properties. However, such compounds present high volatility. To address this issue, a drug delivery system composed of coaxial wet-spun fibers was engineered and different EOs, namely clove oil (CO), cinnamon leaf oil (CLO) and tea tree oil (TTO), were loaded. Briefly, a coaxial system composed of two syringe pumps, a coagulation bath of deionized water, a cylindrical-shaped collector and a coaxial spinneret was used. A 10 % w/v polycaprolactone (PCL) solution was combined with the different EOs at 2 × minimum bactericidal concentration (MBC) and loaded to a syringe connected to the inner port, whereas a 10 % w/v cellulose acetate (CA) solution mixed with 10 % w/v polyethylene glycol (PEG) at a ratio of 90:10 % v/v (to increase the fibers' elasticity) was loaded to the syringe connected to the outer port. This layer was used as a barrier to pace the release of the entrapped EO. The CA's inherent porosity in water coagulation baths allowed access to the fiber's core. CA was also mixed with 10 % w/v polyethylene glycol (PEG) at a ratio of 90:10 % v/v (CA:PEG), to increase the fibers' elasticity. Microfibers maintained their structural integrity during 28 days of incubation in physiological-like environments. They also showed high elasticities (maximum elongations at break >300 %) and resistance to rupture in mechanical assessments, reaching mass losses of only ≈ 2.29 % - 57.19 %. The EOs were released from the fibers in a prolonged and sustained fashion, in which ≈ 30 % of EO was released during the 24 h of incubation in physiological-like media, demonstrating great antibacterial effectiveness against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Pseudomonas aeruginosa, the most prevalent bacteria in chronic wounds. Moreover, microfibers showed effective antioxidant effects, presenting up to 59 % of reduction of 2,2-diphenyl-1-picrylhydrazyl (DPPH) activity. Furthermore, the coaxial system was deemed safe for contact with fibroblasts and human keratinocytes, reaching metabolic activities higher than 80 % after 48 h of incubation. Data confirmed the suitability of the engineered system for potential therapeutics of chronic wounds.

Clinical value of Vitamin-D combined with budesonide/formoterol and theophylline sodium glycinate sustained-release tablets in the treatment of chronic obstructive pulmonary disease patients.

Objective: To explore the clinical value of Vitamin-D combined with budesonide/formoterol (BF) and theophylline sodium glycinate (TSG) sustained-release tablets in the treatment of patients with chronic obstructive pulmonary disease (COPD). Methods: Medical records of 114 patients with CODP, treated in Wenzhou Geriatric Hospital from October 2020 to February 2023, were retrospectively analyzed. Of them, 59 received treatment with Vitamin-D combined with BF and TSG sustained-release tablets (Group-A), and 55 patients received treatment with BF combined with TSG sustained-release tablets (Group-B). Lung function indicators, blood gas status, inflammatory factors, fractional exhaled nitric oxide (FeNO), and 25-hydroxyvitamin D [25(OH)D] levels before and after the treatment in both groups were collected. Results: After the treatment, lung function indicators, blood gas status, inflammatory factors, FeNO, and 25 (OH) D levels in both groups were significantly improved compared to pretreatment levels, and were significantly better in the Group-A compared to Group-B (P<0.05). Conclusions: The combination of Vitamin-D, BF, and TSG sustained-release tablets can effectively regulate the blood gas status of patients with COPD, improve lung function, regulate FeNO and 25 (OH) D, and effectively downregulate the levels of inflammatory factors, thus reducing the degree of inflammatory response.

Sustained release of 3D printed bupropion hydrochloride tablets bearing Braille imprints for the visually impaired.

3D printing has been introduced as a novel approach for the design of personalized dosage forms and support patient groups with special needs that require additional assistance for enhanced medication adherence. In this study liquid crystal display (LCD) is introduced for the development of sustained release bupropion.HCl printed tablets. The optimization of printing hydrogel inks was combined with the display of Braille patterns on the tablet surface for blind or visually impaired patients. Due to the high printing accuracy, the Braille patterns could be verified by blind patients and provide the required information. Further characterization revealed the presence of BUP in amorphous state within the photopolymerized resins. The selection of poly(ethylene glycol) (PEG)-diacrylate (PEGDA) of different molecular weights and the presence of surfactants or solubilizers disrupted the resin photopolymerization, thus controlling the BUP dissolution rates. A small batch scale-up study demonstrated the capacity of LCD to print rapidly a notable number of tablets within 24 min.

Sustained-release of SOD from multivesicular liposomes accelerated the colonic mucosal healing of colitis mice by inhibiting oxidative stress.

Oxidative stress has long been known as a pathogenic factor of ulcerative colitis. Superoxide dismutase (SOD) has been demonstrated to mitigate gut mucosal injury via combating oxidative stress. Herein, we developed SOD-loaded multivesicular liposomes (S-MVLs) as sustained-release depot for ulcerative colitis treatment. S-MVLs were spherical honeycomb-like particles with average particle size of 27.3 ± 5.4 µm and encapsulating efficiency of 78.7 ± 2.6 %. Moreover, the two-phase release profiles of SOD from S-MVLs were exhibited, that was, the burst release phase within 4 h and the sustained-release phase within 96 h. After intraperitoneally injecting S-MVLs, in situ retention time of SOD at bowel cavity extended by 4-fold in comparison with SOD solution. In vitro cells experiment showed that S-MVLs had the protective effect on LPS-treated RAW 264.7 cells via scavenging ROS and inhibiting pro-inflammatory cytokines production. S-MVLs ameliorated the body weight loss, DAI score and the colon shortening of colitis mice. Meanwhile, the colonic morphology and the epithelial barrier of colitis mice were effectively recovered after S-MVLs treatment. The therapeutic mechanism might be associated with polymerizing M1 macrophages to M2 phenotypes and alleviating oxidative stress. Collectively, multivesicular liposomes might be a promising sustained-release depot of SOD for ulcerative colitis treatments.

Stability Development, Optimization and Evaluation of Gastro-Retentive Microspheres of Antidiabetic Agent by Full Factorial Design.

OBJECTIVE: This work is aimed to Formulate, Optimize and Evaluate Gastro-Retentive Microspheres of Antidiabetic Agent by Full Factorial Design. METHODS: Microspheres were prepared using Emulsification-cross linking technique. To this HPMC-K4M and Carbopol was dissolved in 250 ml of water and allowed to swell for 24 hr at room temperature. And separately chitosan was dissolved in 3% (v/v) glacial acetic acid and this also kept for 24 h to swell or dissolve properly. After 24hr this swelled mixture was mixed under magnetic stirrer (Remi, India) at specific stirring rate for 1hr in order to find homogeneous mass of both the gum. Then slurry of chitosan also was homogenized for half an hour. The drug, Glipizide (1g) was then added to the chitosan solution and mixed homogenesously. RESULTS: The aim of the study was to formulate and evaluate microspheres, for Gastro-Retentive Microspheres of the chosen drug. The EE of microspheres was found to be 91.52%, maximum . Buoyancy property observed was 93.82% for Optimized formulation F-9, Drug release 57.34% till 8 h. The work also aims to study various parameters affecting the behaviour of microspheres in oral dosage form. CONCLUSION: Drugs with short half-life that are absorbed from the gastrointestinal tract (GIT) are eliminated rapidly from the blood flow. To avoid this, the oral SR Gastro-retentive was developed as this formulation released the drug slowly into the GIT and maintained a stable drug concentration in the serum for a longer duration of time.

Polystyrene Sulfonate Resin as an Ophthalmic Carrier for Enhanced Bioavailability of Ligustrazine Phosphate Controlled Release System.

Topical ocular sustained-release drug delivery systems represent an effective strategy for the treatment of ocular diseases, for which a suitable carrier has yet to be sufficiently developed. Herein, an eye-compatible sodium polystyrene sulfonate resin (SPSR) was synthesized with a uniform particle size of about 3 µm. Ligustrazine phosphate (LP) was adsorbed to SPSR by cation exchange to form LP@SPSR. LP@SPSR suspension eye drops were further developed using the combination of Carbopol 934P and xanthan gum as suspending agents. The LP@SPSR suspension showed a sustained release in vitro, which was consistent with the observed porcine corneal penetration ex vivo. Pharmacokinetics in tear fluid of rabits indicated that LP@SPSR suspension led to prolonged ocular retention of LP and a 2-fold improved the area under the drug concentration-time curve (AUC0-t). Pharmacokinetics in the aqueous humor of rabbits showed 2.8-fold enhancement in the AUC0-t compared to LP solution. The LP@SPSR suspension exhibited no cytotoxicity to human corneal epithelial cells, nor irritation was observed in rabbit eyes. Thus, the LP@SPSR suspension has been validated as a safe and sustained release system leading to enhanced ophthalmic bioavailability for treating ocular diseases.

Advancing inflammatory skin disease therapy: Sustained tofacitinib release via electrospun fiber dressings.

Inflammatory skin diseases are typically managed with semi-solid formulations such as creams and ointments. These treatments often fail to remain on the skin for long, as they can be easily wiped off by clothing, necessitating frequent reapplication throughout the day and resulting in poor patient adherence. Therefore, this study sought to fabricate an electrospun dressing as an alternative dosage form that provides a sustained release of the anti-inflammatory agent tofacitinib over three days. In this study, three types of electrospun fiber dressings - uniaxial, coaxial, and layer-by-layer - were produced and examined for their morphological, mechanical, and release characteristics. In addition to a comprehensive characterization, another objective was to analyze the drug permeation behavior from these fiber dressings on porcine skin, comparing their performance to that of a tofacitinib cream. The layer-by-layer system notably exhibited a delayed drug release, while the uniaxial and coaxial systems demonstrated an initial burst release. However, the permeation studies revealed no significant differences between these systems, underscoring the necessity of conducting such studies - a crucial aspect often overlooked in research on electrospun fiber dressings. Overall, this study highlights the potential of electrospun, drug-loaded dressings for the treatment of inflammatory skin diseases.

Design of berberine hydrochloride sustained-release cold sol using hydroxypropyl methyl cellulose K100M to achieve superior drug dissolution and transdermal absorption.

In this study, berberine hydrochloride (Ber) was used as model drug to prepare a sustained-release cold sol using hydroxypropyl methyl cellulose (HPMC) to achieve superior drug dissolution and transdermal absorption effects. For comparison, a Ber cold sol without HPMC was also prepared using the same method. The preparation process was optimized based on the in vitro release and transdermal permeability of the drug. The results indicated that 1.67 wt% Carbomer 940 and 1.33 wt% HPMC K100M were selected as matrix components with the best sustained-release effect, and drug dissolution of cold sol prepared by combination of these two matrices was significantly slower than the cold sol without HPMC. In addition, transdermal absorption result demonstrated that 0.67 wt% glycerin and 1.33 wt% peppermint oil were the best osmotic enhancers for the optimization of Ber sustained-release cold sol. Herein, HPMC K100M performed important functions in the external application of Ber.

pH-responsive chitosan-mediated spherical mesoporous silica microspheres for high loading and controlled delivery of 5-Fluorouracil.

The objective of this study is to develop a drug carrier to overcome the inherent drawbacks of 5-Fluorouracil (5-Fu), including low bioavailability, short half-life, and systemic toxicity. In the present work, mesoporous silica nanoparticles (MSNs) capped by chitosan (CS) to encapsulate 5-Fu (5-Fu MSNs/CS) were fabricated by the sol-gel process, ultrasonic impregnation, and emulsion cross-linking. The 5-Fu MSNs/CS microspheres exhibit pH-responsive drug release and remarkable drug encapsulation capacity, as well as perfect sphericity, high specific surface area (680.62 cm2/g), and uniform particle size (2.64 ± 0.05 µm). The drug-loading content and encapsulation efficiency are 14.12 ± 0.53 % and 82.21 ± 2.13 %, respectively. The cumulative release of 5-Fu from MSNs/CS microspheres is fast and sustained at pH 5.0 (89.56 ± 0.97 %) compared to that at pH 7.4 (57.88 ± 0.91 %) in 96 h, and it is Fickian diffusion controlled. In conclusion, the MSNs/CS microspheres prepared in this study could be potential carriers for 5-Fu delivery.

Multifunctional and bioinspired titanium surface with multilayer nanofilms for novel dental implant applications.

Introduction: Smart multifunctional surfaces targeting intricate biological events or versatile therapeutic strategies are imminent to achieve long-term transmucosal implant success. Methods: This study used dopamine (DA), graphene oxide (GO), and type IV collagen (COL-IV) to construct multilayer nanofilms (DGCn) based on their universal adhesive and biomimetic properties to design a versatile and bioactive titanium implant. The characterization of DGCn on different titanium surfaces was performed, and its loading capacity, release profile, in situ gene delivery, and in vitro biological properties were preliminarily evaluated. Results: Our results demonstrate that hydrogenated TiO2 nanotubes (H) provide a better platform for the DGCn coating than machined Ti and air-TiO2 nanotubes. The H-DGC10 displayed the most stable surface with excellent loading capacity, sustained-release profile, and in situ gene transfection efficiency; this could be due to the high specific surface area of H and GO, as well as the functional groups in H, DA, and GO. Moreover, the H-DGC10 exhibited good biocompatibility for human oral epithelial cells and promoted the expression of integrin ß4 and laminin 332, both being hemidesmosome-related proteins. Discussion: Our findings suggest that H-DGCn can be designed as a smart multifunctional interface for titanium implants to achieve long-term transmucosal implant success and aid in versatile therapeutic strategies.

Immunomodulatory effect of PLGA-encapsulated mesenchymal stem cells-derived exosomes for the treatment of allergic rhinitis.

Introduction: Allergic rhinitis (AR) is an upper airway inflammatory disease of the nasal mucosa. Conventional treatments such as symptomatic pharmacotherapy and allergen-specific immunotherapy have considerable limitations and drawbacks. As an emerging therapy with regenerative potential and immunomodulatory effect, mesenchymal stem cell-derived exosomes (MSC-Exos) have recently been trialed for the treatment of various inflammatory and autoimmune diseases. Methods: In order to achieve sustained and protected release of MSC-Exos for intranasal administration, we fabricated Poly(lactic-co-glycolic acid) (PLGA) micro and nanoparticles-encapsulated MSC-Exos (PLGA-Exos) using mechanical double emulsion for local treatment of AR. Preclinical in vivo imaging, ELISA, qPCR, flow cytometry, immunohistochemical staining, and multiomics sequencing were used for phenotypic and mechanistic evaluation of the therapeutic effect of PLGA-Exos in vitro and in vivo. Results: The results showed that our PLGA platform could efficiently encapsulate and release the exosomes in a sustained manner. At protein level, PLGA-Exos treatment upregulated IL-2, IL-10 and IFN-γ, and downregulated IL-4, IL-17 and antigen-specific IgE in ovalbumin (OVA)-induced AR mice. At cellular level, exosomes treatment reduced Th2 cells, increased Tregs, and reestablished Th1/Th2 balance. At tissue level, PLGA-Exos significantly attenuated the infiltration of immune cells (e.g., eosinophils and goblet cells) in nasal mucosa. Finally, multiomics analysis discovered several signaling cascades, e.g., peroxisome proliferator-activated receptor (PPAR) pathway and glycolysis pathway, that might mechanistically support the immunomodulatory effect of PLGA-Exos. Discussion: For the first time, we present a biomaterial-facilitated local delivery system for stem cell-derived exosomes as a novel and promising strategy for AR treatment.