Delivery Vehicles Research Articles

In Vitro and In Vivo Studies of Titanium Dioxide Nanoparticles with Galactose Coating as a Prospective Drug Carrier.

In today's medicine, progress often depends on new products with special qualities. Nanotechnology focuses on the creation of materials tailored to fulfill specific therapeutic requirements. This study aims to elucidate the potential of nanoparticles, particularly titanium dioxide nanoparticles, as carriers for pharmaceutical agents. To mitigate the release of potentially harmful titanium ions from the carrier's surface, modifications were implemented. In the initial phase, titanium dioxide, nanoparticles were obtained based on the sol-gel method, and their surfaces were coated with galactose. Characterization of these materials encompassed analysis of the particle size, specific surface area, microscopic morphology, and titanium ion release. Additionally, drug release profiles, particularly those of tadalafil, were investigated. In vitro assessments were conducted to evaluate the cytotoxic and mutagenic effects of the developed materials on CHO cells. The findings revealed a reduction in titanium ion release from the modified carrier compared to its unmodified counterpart. Pharmacokinetic studies in rats demonstrated enhanced absorption of the drug when the drug was delivered using the modified carrier. The synthesized materials exhibited high purity and favorable surface properties conducive to effective drug-carrier interactions. The results suggest that the modified titanium dioxide nanoparticles hold promise as efficient drug delivery vehicles in biomedical applications.

Electrochemical and surface characterisation of poly(3,4-ethylenedioxythiophene) dodecylbenzenesulfonate layers

Poly(3,4-ethylenedioxythiophene) (PEDOT) films were electrochemically synthesised with sodium dodecylbenzenesulfonate (DBS) and chloride acting as dopant anions within the polymer matrix. Upon redox switching of the PEDOT/DBS film between conducting and non-conducting states, the DBS anion remained within the polymer and cation insertion and expulsion occurred, as confirmed by Electrochemical Quartz Crystal Microbalance (EQCM) measurements. Electrolytes composed of alkali metal cations of varying masses (Li+, Na+, K+) were employed to investigate the cation insertion/expulsion processes, thereby resulting in varying mass changes being observed upon film redox switching. The charging and discharging of bulky anion doped polymer films presented higher capacitance upon charging and lower capacitance when discharging, which is expected during doping and de-doping as confirmed by AC impedance. In this work, the main results obtained by chemical-physical characterisation are presented and critically discussed, with regard to the possible use of a viable conducting polymer as a drug delivery vehicle.

Redox-Responsive AIEgen Diselenide-Covalent Organic Framework Composites Targeting Hepatic Macrophages for Treatment of Drug-induced Liver Injury.

The escalating misuse of antipyretic and analgesic drugs, alongside the rising incidents of acute drug-induced liver injury, underscores the need for a precisely targeted drug delivery system. Herein, two isoreticular covalent organic frameworks (Se-COF and Se-BCOF) are developed by Schiff-base condensation of emissive tetraphenylethylene and diselenide-bridged monomers. Leveraging the specific affinity of macrophages for mannose, the first precise targeting of these COFs to liver macrophages is achieved. The correlation is also explored between the therapeutic effects of COFs and the NLRP3/ASC/Caspase-1 signaling pathway. Utilizing this innovative delivery vehicle, the synergistic delivery of matrine and berberine are accomplished, compounds extracted from traditional Chinese medicine. This approach not only demonstrated the synergistic effects of the drugs but also mitigated their toxicity. Notably, berberine, through phosphorylation of JNK and up-regulation of nuclear Nrf-2 and its downstream gene Mn-SOD expression, simultaneously countered excessive ROS and suppressed the activation of the NLRP3/ASC/Caspase-1 signaling pathway in injured liver tissues. This multifaceted approach proved highly effective in safeguarding against acute drug-induced liver injury, ultimately restoring liver health to normalcy. These findings present a novel and promising strategy for the treatment of acute drug-induced liver injury.

Location-routing optimization of UAV collaborative blood delivery vehicle distribution on complex roads

To address the protracted blood transportation time prevalent in contemporary urban settings, we proposed a location-routing optimization problem tailored to the distribution of blood within intricate road networks. This involved a comprehensive assessment that encompassed the judicious selection of sites for both stations and blood centers, coupled with the meticulous planning of delivery routes for unmanned aerial vehicles (UAVs) that orchestrate the transportation of blood. First, a model was formulated to minimize the overall cost, including transportation expenses, costs associated with the site, and other relevant costs related to blood transportation vehicles coordinated by UAVs. Subsequently, a two-stage hybrid heuristic algorithm was designed based on the distinctive characteristics of the problem at hand. Moreover, an enhanced k-means algorithm was employed to generate clustering schemes, utilizing the centroid method to address the challenge of location selection for delivery sites effectively. A genetic algorithm enhanced with adaptive operators was employed to address the challenging large-scale NP-hard problem associated with route planning in intricate urban road networks. The results indicated that, compared to the traditional blood delivery model using vehicles, the total blood transportation cost decreased by 12.65% and the overall delivery time was reduced by 37.5% with the adoption of drone-assisted delivery; ultimately, case and sensitivity analyses were conducted to investigate the impact of variables including the number of blood transportation vehicles, UAVs, driver wages, and unit costs of blood transportation vehicles on the location-routing problem.

Hyaluronic Acid-Based Microparticles with Lubrication and Anti-Inflammation for Alleviating Temporomandibular Joint Osteoarthritis.

The pathogenesis of temporomandibular joint osteoarthritis (TMJOA) is closely associated with mechanical friction, which leads to the up-regulation of inflammatory mediators and the degradation of articular cartilage. Injectable drug-loaded microparticles have attracted widespread interest in intra-articular treatment of TMJOA by providing lubrication and facilitating localized drug delivery. Herein, a hyaluronic acid-based microparticle is developed with excellent lubrication properties, drug loading capacity, antioxidant activity, and anti-inflammatory effect for the treatment of TMJOA. The microparticles are facilely prepared by the self-assembly of 3-aminophenylboronic acid-modified hyaluronic acid (HP) through hydrophobic interaction in an aqueous solution, which can further encapsulate diol-containing drugs through dynamic boronate ester bonds. The resulting microparticles demonstrate excellent injectability, lubrication properties, radical scavenging efficiency, and antibacterial activity. Additionally, the drug-loaded microparticles exhibit a favorable cytoprotective effect on chondrocyte cells invitro under an oxidative stress microenvironment. Invivo experiments validate that intra-articular injection of drug-loaded microparticles effectively alleviates osteoporosis-like damage, suppresses inflammatory response, and facilitates matrix regeneration in the treatment of TMJOA. The HP microparticles demonstrate excellent injectability and encapsulation capacity for diol-containing drugs, highlighting its potential as a versatile drug delivery vehicle in the intra-articular treatment of TMJOA.

Optimizing omnichannel retailer inventory replenishment using vehicle capacity-sharing with demand uncertainties and service level requirements

This study explores an inventory replenishment problem for an omnichannel retailer selling a product with demand uncertainties and service level requirements in different channels through a capacity-sharing strategy. The omnichannel retailer allows customers to order products online and then pick them up in retail stores. The capacity-sharing strategy is considered to reduce travel costs when the omnichannel retailer delivers products in different channels. With the capacity-sharing strategy, some products can be transferred from the online delivery vehicle to the retail store delivery vehicle. The expectation and the bounds on the online route travel cost of the capacity-sharing strategy are determined, based on which the capacity-sharing rules are established. Optimization models and a solution procedure are developed to solve the omnichannel retailer inventory replenishment problem. To ensure adequate performance, service level requirements are considered when making delivery decisions. Numerical experiments using randomly generated and artificial instances are performed to verify the effectiveness and practicality of the proposed optimization models and the solution procedure. The results show that the proposed models and solution procedure can effectively reduce travel costs, and can provide effective schedule and delivery quantity decision support for omnichannel retailers.

Actively Targeting Redox-Responsive Multifunctional Micelles for Synergistic Chemotherapy of Cancer.

Stimuli-responsive polymeric micelles decorated with cancer biomarkers represent an optimal choice for drug delivery applications due to their ability to enhance therapeutic efficacy while mitigating adverse side effects. Accordingly, we synthesized a digoxin-modified novel multifunctional redox-responsive disulfide-linked poly(ethylene glycol-b-poly(lactic-co-glycolic acid) copolymer (Bi(Dig-PEG-PLGA)-S2) for the targeted and controlled release of doxorubicin (DOX) in cancer cells. Within the micellar aggregate, the disulfide bond confers redox responsiveness, while the presence of the digoxin moiety acts as a targeting agent and chemosensitizer for DOX. Upon self-assembly in aqueous solution, Bi(Dig-PEG-PLGA)-S2 formed uniformly distributed spherical micelles with a hydrodynamic diameter (D h ) of 58.36 ± 0.78 nm and a zeta potential of -24.71 ± 1.01 mV. The micelles exhibited desirable serum and colloidal stability with a substantial drug loading capacity (DLC) of 6.26% and an encapsulation efficiency (EE) of 83.23%. In addition, the release of DOX demonstrated the redox-responsive behavior of the micelles, with approximately 89.41 ± 6.09 and 79.64 ± 6.68% of DOX diffusing from DOX@Bi(Dig-PEG-PLGA)-S2 in the presence of 10 mM GSH and 0.1 mM H2O2, respectively, over 96 h. Therefore, in HeLa cell lines, DOX@Bi(Dig-PEG-PLGA)-S2 showed enhanced intracellular accumulation and subsequent apoptotic effects, attributed to the targeting ability and chemosensitization potential of digoxin. Hence, these findings underscore the promising characteristics of Bi(Dig-PEG-PLGA)-S2 as a multifunctional drug delivery vehicle for cancer treatment.

Inhaled Ivermectin-Loaded Lipid Polymer Hybrid Nanoparticles: Development and Characterization.

Ivermectin (IVM), a drug originally used for treating parasitic infections, is being explored for its potential applications in cancer therapy. Despite the promising anti-cancer effects of IVM, its low water solubility limits its bioavailability and, consequently, its biological efficacy as an oral formulation. To overcome this challenge, our research focused on developing IVM-loaded lipid polymer hybrid nanoparticles (LPHNPs) designed for potential pulmonary administration. IVM-loaded LPHNPs were developed using the emulsion solvent evaporation method and characterized in terms of particle size, morphology, entrapment efficiency, and release pattern. Solid phase characterization was investigated by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Using a Twin stage impinger (TSI) attached to a device, aerosolization properties of the developed LPHNPs were studied at a flow rate of 60 L/min, and IVM was determined by a validated HPLC method. IVM-loaded LPHNPs demonstrated spherical-shaped particles between 302 and 350 nm. Developed formulations showed an entrapment efficiency between 68 and 80% and a sustained 50 to 60% IVM release pattern within 96 h. Carr's index (CI), Hausner ratio (HR), and angle of repose (θ) indicated proper flowability of the fabricated LPHNPs. The in vitro aerosolization analysis revealed fine particle fractions (FPFs) ranging from 18.53% to 24.77%. This in vitro study demonstrates the potential of IVM-loaded LPHNPs as a delivery vehicle through the pulmonary route.

Enhanced Efficacy of Gastric Cancer Treatment through Targeted Exosome Delivery of 17-DMAG Anticancer Agent.

In this study, we explored the potential of genetically engineered exosomes as vehicles for precise drug delivery in gastric cancer therapy. A novel antitumor strategy using biocompatible exosomes (Ex) was devised by genetically engineering adipose-derived stem cells to express an MKN45-binding peptide (DE532) on their surfaces. 17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG) was encapsulated in engineered exosomes, resulting in 17-DMAG-loaded DE532 exosomes. In both in vitro and in vivo experiments using mouse gastric cancer xenograft models, we demonstrated that 17-DMAG-loaded DE532 Ex exhibited superior targetability over DE532 Ex, 17-DMAG-loaded Ex, and Ex. Administration of the 17-DMAG-loaded DE532 Ex yielded remarkable antitumor effects, as evidenced by the smallest tumor size, lowest tumor growth rate, and lowest excised tumor weight. Further mechanistic examinations revealed that the 17-DMAG-loaded DE532 Ex induced the highest upregulation of the pro-apoptotic marker B-cell lymphoma-2-like protein 11 and the lowest downregulation of the anti-apoptotic marker B-cell lymphoma-extra large. Concurrently, the 17-DMAG-loaded DE532 Ex demonstrated the lowest suppression of antioxidant enzymes, such as superoxide dismutase 2 and catalase, within tumor tissues. These findings underscore the potential of 17-DMAG-loaded DE532 exosomes as a potent therapeutic strategy for gastric cancer, characterized by precise targetability and the potential to minimize adverse effects.

Elastin-Derived Peptide-Based Hydrogels as a Potential Drug Delivery System.

A peptide-based hydrogel sequence was computationally predicted from the Ala-rich cross-linked domains of elastin. Three candidate peptides were subsequently synthesised and characterised as potential drug delivery vehicles. The elastin-derived peptides are Fmoc-FFAAAAKAA-NH2, Fmoc-FFAAAKAA-NH2, and Fmoc-FFAAAKAAA-NH2. All three peptide sequences were able to self-assemble into nanofibers. However, only the first two could form hydrogels, which are preferred as delivery systems compared to solutions. Both of these peptides also exhibited favourable nanofiber lengths of at least 1.86 and 4.57 µm, respectively, which are beneficial for the successful delivery and stability of drugs. The shorter fibre lengths of the third peptide (maximum 0.649 µm) could have inhibited their self-assembly into the three-dimensional networks crucial to hydrogel formation.

Oral drug delivery vehicle for insulin and curcumin based on egg albumin-dextran conjugate: In vitro and in vivo studies

The increasing desire for oral delivery vehicle systems encouraged the development of micro and nano encapsulation technologies to protect drugs against gastric and enzymatic degradation. This study aimed to develop egg albumin-dextran conjugate as a delivery vehicle for oral administration. For this purpose, insulin was selected as a macromolecule drug and curcumin as a natural lipophilic polyphenol, both show negative absorption kinetics in gastrointestinal tract. Egg albumin-dextran conjugate was prepared by Maillard reaction under mild conditions and subsequently be used to encapsulate insulin and curcumin, respectively. The encapsulation efficiency reached to 97 % and 95.5 % at 300 mg/ml of insulin and curcumin, respectively. The profile of in vitro drug release for the insulin and curcumin indicates that approximately 60 % of the drugs were partially retained by the conjugate in gastric pH environment while a more extensive release was observed under intestinal pH conditions. Application of oral administration of insulin conjugate (IC) and/or curcumin conjugate (CC) to streptozotocin (STZ) induced diabetic rats was investigated for 6 weeks and compared with trade insulin drug. Fifty-four albino rats were separated into nine equivalent groups. Control, insulin conjugate (IC), curcumin conjugate (CC), and IC + CC. The remaining groups injected with STZ and subsequently received vehicle, IC, CC, IC + CC, and trade insulin drug; respectively.Interestingly, insulin conjugate and/or curcumin conjugate significantly reduced hyperglycemia, hyperlipidemia, decreased fructosamine level, decreased HOMA-IR, increased insulin level, increased HOMA-β, increased antioxidant defense molecules, along with modulating morphological pancreatic degeneration caused by STZ. In conclusion, oral insulin-conjugate is more effective than the trade insulin drug. Also, curcumin-conjugate has a promising role as antidiabetic agent as it may contribute in β-cells regeneration. Further, the combination between them may have synergetic antidiabetic effect. But, more detailed studies should be done to investigate the possible mechanisms of their antidiabetic effect.

Marine Delivery Vehicles: Molecular Components and Applications of Bacterial Extracellular Vesicles.

In marine ecosystems, communication among microorganisms is crucial since the distance is significant if considered on a microbial scale. One of the ways to reduce this gap is through the production of extracellular vesicles, which can transport molecules to guarantee nutrients to the cells. Marine bacteria release extracellular vesicles (EVs), small membrane-bound structures of 40 nm to 1 µm diameter, into their surrounding environment. The vesicles contain various cellular compounds, including lipids, proteins, nucleic acids, and glycans. EVs may contribute to dissolved organic carbon, thus facilitating heterotroph growth. This review will focus on marine bacterial EVs, analyzing their structure, composition, functions, and applications.

Unlocking the potential of beta-glucans: a comprehensive review from synthesis to drug delivery carrier potency.

Modernization and lifestyle changes have resulted in a number of diseases, including cancer, that require complicated and thorough treatments. One of the most important therapies is the administration of antibiotics and medicines. This is known as chemotherapy for cancer, and it is a regularly utilised treatment plan in which the medications used have negative side effects. This has resulted in extensive research on materials capable of delivering pharmaceuticals to particular targets over an extended period of time. Biopolymers have often been preferred as effective drug delivery carriers. Of these, β-glucan, a natural polysaccharide, has not been extensively studied as a drug delivery carrier, despite its unique properties. This review discusses the sources, extraction techniques, structures, and characteristics of β-glucan to provide an overview. Furthermore, the different methods employed to encapsulate drugs into β-glucan and its role as an efficient drug, SiRNA and Plasmid DNA carrier have been elaborated in this article. The capacity of β-glucan-based to specifically target and alter tumour-associated macrophages, inducing an immune response ultimately resulting in tumour suppression has been elaborated. Finally, this study aims to stimulate further research on β-glucan by thoroughly describing its many characteristics and demonstrating its effectiveness as a drug delivery vehicle.

Functionalized Mesoporous Silica Nanoparticles as Potential Drug Delivery Vehicle against Colorectal Cancer

Functionalized Mesoporous Silica Nanoparticles as Potential Drug Delivery Vehicle against Colorectal Cancer

Delivery vehicle and route of administration influences self-amplifying RNA biodistribution, expression kinetics, and reactogenicity

Self-amplifying RNA (saRNA) is a next-generation RNA platform derived from an alphavirus that enables replication in host cytosol, offering a promising shift from traditional messenger RNA (mRNA) therapies by enabling sustained protein production from minimal dosages. The approval of saRNA-based vaccines, such as the ARCT-154 for COVID-19 in Japan, underscores its potential for diverse therapeutic applications, including vaccine development, cancer immunotherapy, and gene therapy. This study investigates the role of delivery vehicle and administration route on saRNA expression kinetics and reactogenicity. Employing ionizable lipid-based nanoparticles (LNPs) and polymeric nanoparticles, we administered saRNA encoding firefly luciferase to BALB/c mice through six routes (intramuscular (IM), intradermal (ID), intraperitoneal (IP), intranasal (IN), intravenous (IV), and subcutaneous (SC)), and observed persistent saRNA expression over a month. Our findings reveal that while LNPs enable broad route applicability and stability, pABOL (poly (cystamine bisacrylamide-co-4-amino-1-butanol)) formulations significantly amplify protein expression via intramuscular delivery. Notably, the disparity between RNA biodistribution and protein expression highlight the nuanced interplay between administration routes, delivery vehicles, and therapeutic outcomes. Additionally, our research unveiled distinct biodistribution profiles and inflammatory responses contingent upon the chosen delivery formulation and route. This research illuminates the intricate dynamics governing saRNA delivery, biodistribution and reactogenicity, offering essential insights for optimizing therapeutic strategies and advancing the clinical and commercial viability of saRNA technologies.

In Situ-Forming, Bioorthogonally Cross-linked, Nanocluster-Reinforced Hydrogel for the Regeneration of Corneal Defects.

Corneal defects can lead to stromal scarring and vision loss, which is currently only treatable with a cadaveric corneal transplant. Although in situ-forming hydrogels have been shown to foster regeneration of the cornea in the setting of stromal defects, the cross-linking, biomechanical, and compositional parameters that optimize healing have not yet been established. This, Corneal defects are also almost universally inflamed, and their rapid closure without fibrosis are critical to preserving vision. Here, an in situ forming, bioorthogonally cross-linked, nanocluster (NC)-reinforced collagen and hyaluronic acid hydrogel (NCColHA hydrogel) with enhanced structural integrity and both pro-regenerative and anti-inflammatory effects was developed and tested within a corneal defect model in vivo. The NCs serve as bioorthogonal nanocross-linkers, providing higher cross-linking density than polymer-based alternatives. The NCs also serve as delivery vehicles for prednisolone (PRD) and the hepatocyte growth factor (HGF). NCColHA hydrogels rapidly gel within a few minutes upon administration and exhibit robust rheological properties, excellent transparency, and negligible swelling/deswelling behavior. The hydrogel's biocompatibility and capacity to support cell growth were assessed using primary human corneal epithelial cells. Re-epithelialization on the NCColHA hydrogel was clearly observed in rabbit eyes, both ex vivo and in vivo, with expression of normal epithelial biomarkers, including CD44, CK12, CK14, α-SMA, Tuj-1, and ZO-1, and stratified, multilayered morphology. The applied hydrogel maintained its structural integrity for at least 14 days and remodeled into a transparent stroma by 56 days.

Engineering CaP-Pickering emulsion for enhanced mRNA cancer vaccines via dual DC and NK activations

mRNA delivery systems, such as lipid nanoparticle (LNP), have made remarkable strides in improving mRNA expression, whereas immune system activation operates on a threshold. Maintaining a delicate balance between antigen expression and dendritic cell (DC) activation is vital for effective immune recognition. Here, a water-in-oil-in-water (w/o/w) Pickering emulsion stabilized with calcium phosphate nanoparticles (CaP-PME) is developed for mRNA delivery in cancer vaccination. CaP-PME efficiently transports mRNA into the cytoplasm, induces pro-inflammatory responses and activates DCs by disrupting intracellular calcium/potassium ions balance. Unlike LNP, CaP-PME demonstrates a preference for DCs, enhancing their activation and migration to lymph nodes. It elicits interferon-γ-mediated CD8+ T cell responses and promotes NK cell proliferation and activation, leading to evident NK cells infiltration and ameliorated tumor microenvironment. The prepared w/o/w Pickering emulsion demonstrates superior anti-tumor effects in E.G7 and B16-OVA tumor models, offering promising prospects as an enhanced mRNA delivery vehicle for cancer vaccinations.

Therapeutic targeting of siRNA/anti-cancer drug delivery system for non-melanoma skin cancer. Part I: Development and gene silencing of JAK1siRNA/5-FU loaded liposome nanocomplexes

Non-melanoma skin cancer (NMSC) is one of the most prevalent cancers, leading to significant mortality rates due to limited treatment options and a lack of effective therapeutics. Janus kinase (JAK1), a non-receptor tyrosine kinase family member, is involved in various cellular processes, including differentiation, cell proliferation and survival, playing a crucial role in cancer progression. This study aims to provide a more effective treatment for NMSC by concurrently silencing the JAK1 gene and administering 5-Fluorouracil (5-FU) using liposome nanocomplexes as delivery vehicles. Utilizing RNA interference (RNAi) technology, liposome nanocomplexes modified with polyethylene imine (PEI) were conjugated with siRNA molecule targeting JAK1 and loaded with 5-FU. The prepared formulations (NL-PEI) were characterized in terms of their physicochemical properties, morphology, encapsulation efficiency, in vitro drug release, and stability. Cell cytotoxicity, cell uptake and knockdown efficiency were evaluated in human-derived non-melanoma epidermoid carcinoma cells (A-431). High contrast transmission electron microscopy (CTEM) images and dynamic light scattering (DLS) measurements revealed that the nanocomplexes formed spherical morphology with uniform sizes ranging from 80-120 nm. The cationic NL-PEI nanocomplexes successfully internalized within the cytoplasm of A-431, delivering siRNA for specific sequence binding and JAK1 gene silencing. The encapsulation of 5-FU in the nanocomplexes was achieved at 0.2 drug/lipid ratio. Post-treatment with NL-PEI for 24, 48 and 72 h showed cell viability above 80 % at concentrations up to 8.5 × 101 µg/mL. Notably, 5-FU delivery via nanoliposome formulations significantly reduced cell viability at 5-FU concentration of 5 µM and above (p < 0.05) after 24 h of incubation. The NL-PEI nanocomplexes effectively silenced the JAK1 gene in vitro, reducing its expression by 50 %. Correspondingly, JAK1 protein level decreased after transfection with JAK1 siRNA-conjugated liposome nanocomplexes, leading to a 37 % reduction in pERK (phosphor extracellular signal-regulated kinase) protein expression. These findings suggest that the combined delivery of JAK1 siRNA and 5-FU via liposomal formulations offers a promising and novel treatment strategy for targeting genes and other identified targets in NMSC therapy.

Cellulose nanocrystal-stabilized Pickering emulsion gels as vehicles for follicular delivery of minoxidil

Minoxidil (MXD) is the only topical over-the-counter medicine approved by the United States Food and Drug Administration for the treatment of androgenetic alopecia. For the purpose of targeting the delivery of MXD to dermal papilla in the hair follicle, MXD Pickering emulsion gels were fabricated based on the designability of deep eutectic solvent (DES) and the versatility of cellulose nanocrystal (CNC) and sodium carboxymethyl cellulose (CMC-Na). Structural studies and theoretical calculations results suggest that CNC can stabilize the interface between the MXD-DES and water, leading to the formation of Pickering emulsions. The rheological properties and stabilities of MXD Pickering emulsions were enhanced through gelation using CMC-Na, which highlights the good compatibility and effectiveness of natural polysaccharides in emulsion gels. Due to the particle size of emulsion droplets (679 nm) and the rheological properties of emulsion gel, the fabricated MXD formulations show in vivo hair regrowth promotion and hair follicle targeting capabilities. Interestingly, the MXD Pickering emulsion-based formulations exert therapeutic effects by upregulating the expression of hair growth factors. The proposed nanodrug strategy based on supramolecular strategies of CNC and CMC-Na provides an interesting avenue for androgenetic alopecia treatment.

Injectable hydrogel encapsulating siMMP13 with anti-ROS and anti-apoptotic functions for osteoarthritis treatment

BackgroundOsteoarthritis (OA) is a degenerative joint disease characterized by the progressive degeneration of articular cartilage, leading to pain, stiffness, and loss of joint function. The pathogenesis of OA involves multiple factors, including increased intracellular reactive oxygen species (ROS), enhanced chondrocyte apoptosis, and disturbances in cartilage matrix metabolism. These processes contribute to the breakdown of the extracellular matrix (ECM) and the loss of cartilage integrity, ultimately resulting in joint damage and dysfunction. RNA interference (RNAi) therapy has emerged as a promising approach for the treatment of various diseases, including hATTR and acute hepatic porphyria. By harnessing the natural cellular machinery for gene silencing, RNAi allows for the specific inhibition of target genes involved in disease pathogenesis. In the context of OA, targeting key molecules such as matrix metalloproteinase-13 (MMP13), which plays a critical role in cartilage degradation, holds great therapeutic potential.ResultsIn this study, we developed an innovative therapeutic approach for OA using a combination of liposome-encapsulated siMMP13 and NG-Monomethyl-L-arginine Acetate (L-NMMA) to form an injectable hydrogel. The hydrogel served as a delivery vehicle for the siMMP13, allowing for sustained release and targeted delivery to the affected joint. Experiments conducted on destabilization of the medial meniscus (DMM) model mice demonstrated the therapeutic efficacy of this composite hydrogel. Treatment with the hydrogel significantly inhibited the degradation of cartilage matrix, as evidenced by histological analysis showing preserved cartilage structure and reduced loss of proteoglycans. Moreover, the hydrogel effectively suppressed intracellular ROS accumulation in chondrocytes, indicating its anti-oxidative properties. Furthermore, it attenuated chondrocyte apoptosis, as demonstrated by decreased levels of apoptotic markers.ConclusionIn summary, the injectable hydrogel containing siMMP13, endowed with anti-ROS and anti-apoptotic properties, may represent an effective therapeutic strategy for osteoarthritis in the future.