Quercetin exhibits distinct therapeutic effects on various dermatologic diseases, including atopic dermatitis (AD), which is the most prevalent inflammatory skin disease, and psoriasis. The present study is aimed at developing a gel composed of quercetin-loaded porous microspheres and evaluating its therapeutic efficacy in mice with DNFB (2,4-dinitrofluorobenzene)-induced AD. Carbomer, a high molecular weight, hydrophilic, non-toxic, and non-irritating cross-linked acrylic polymer, was utilized in the formulation. Gel formulations containing carbomer demonstrate excellent adhesive properties and exhibit sustained drug release over 24 hours in our study. Building on prior research, ethyl cellulose-based microspheres of quercetin were prepared using a quasi-emulsion-solvent diffusion method. These microspheres were then dispersed in Carbomer 934 to create the microsphere-containing gel. The effects of the quercetin porous microsphere gel on DNFB-induced AD in mice were assessed through the atopic dermatitis area severity index scoring, spleen index assay, histopathological analysis, and measurement of inflammatory cytokines. Results from the animal studies indicated that the quercetin porous microsphere gel exhibited therapeutic effects. This study demonstrates that the quercetin porous microsphere gel shows promise as a carrier for the topical administration of quercetin in the treatment of AD.

This study aimed to prepare ε-polylysine (ε-PL)-loaded gelatin/sanxan gum (SG) composite aerogel pads via freeze-drying. Here, ε-PL functioned as both a crosslinking agent and an antibacterial component. Three formulations (G1S2, G1S1, G2S1) with different gelatin/SG mass ratios were fabricated. These aerogel pads were characterized by Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM), X-ray diffraction (XRD), and Thermogravimetric analysis (TGA). The results showed that G2S1 had a high-water absorption rate and achieved the highest encapsulation efficiency for ε-PL (75%). Additionally, it exhibited the strongest antibacterial activity against Staphylococcus aureus, Escherichia coli, Candida albicans, and Aspergillus niger. When applied to banana packaging, G2S1 greatly retarded fruit browning. It also preserved higher levels of total soluble solids and titratable acid, while inhibiting the activities of polyphenol oxidase and peroxidase as well as microbial proliferation. The aerogel pad showed efficient preservation through the antibacterial activity of ε-PL and its inherent ability to regulate the humidity of the storage environment. Our findings demonstrate that the G2S1 aerogel demonstrated favorable potential in enhancing the postharvest preservation effect of fruits, thereby providing a novel insight for the development of green preservation technologies.

Tofacitinib citrate is a novel oral small molecule JAK3 inhibitor that is clinically utilized for the treatment of moderate to severe rheumatoid arthritis in patients who are intolerant or insufficiently responsive to methotrexate. As a treatment for chronic diseases, its osmotic pump-type oral sustained-release formulation has been implemented in clinical practice. This study aimed to evaluate its compatibility with 12 common excipients used in osmotic pump-type oral sustained-release formulations. Compatibility studies were conducted through the preparation of binary mixtures (1:1, w/w) of tofacitinib citrate with the selected excipients. The binary mixtures were analyzed using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and isothermal stress testing (IST). The DSC results indicated that the mixture of maltodextrin and tofacitinib citrate exhibited a new absorption peak, whereas the mixtures of sorbitol and mannitol with tofacitinib citrate resulted in the disappearance of the characteristic absorption peak of tofacitinib citrate, indicating their incompatibility. The results from FTIR and IST further confirmed that maltodextrin is incompatible with tofacitinib citrate and should be avoided in formulation development. Conversely, sorbitol and mannitol were found to be compatible with tofacitinib citrate, as evidenced by the results from FTIR, XRD, and IST. The disappearance of the main peak of tofacitinib citrate in the mixtures was attributed to its dissolution in the molten excipients.

Tofacitinib (Tof), a JAK3 inhibitor, is clinically utilized for the treatment of moderate to severe rheumatoid arthritis (RA). However, long-term oral administration of Tof can lead to serious systemic toxicity and adverse effects. To mitigate its toxicity, this study prepared drug-loaded nanoparticles (NPs), PLGA@Tof, utilizing poly (lactic-co-glycolic acid) PLGA as the matrix. These NPs exhibited a particle size of 220nm, a zeta potential of -13.4mV, drug loading and encapsulation efficiency were 4.12% and 40.57%, and a smooth spherical morphology. In vitro studies demonstrated that these NPs achieved sustained release of Tof without inducing hemolytic effects; less than 50% Tof was released within 24h under pH 5.0 and pH 7.4 conditions. Cellular experiments revealed that the uptake rates of NPs at 1h, 2h, 4h and 8h in RAW264.7 cells were significantly higher than that of the free drug under inflammatory conditions. After 8 h of treatment with PLGA@Tof on inflammatory RAW264.7 cells, the intracellular reactive oxygen species (ROS) level was significantly lower compared to the free Tof treatment group, while the levels of TNF-alpha, IL-1 beta and IL-6 were also significantly reduced in the PLGA@Tof treatment group. These findings suggest that PLGA@Tof has the potential to be developed into a long-acting nanotherapeutic agent for systemic or localized injection in the treatment of RA.

Plant protein-polysaccharide-stabilized high internal phase emulsions (HIPEs) are of great interest in the food industry. In this study, yellow mustard seed protein (YMP) - chitosan (CS)/chitosan oligosaccharide (COS) Maillard conjugates were employed to prepare HIPEs as mayonnaise replacers. The conjugates formation was confirmed by UV-absorbance at 294/420 nm and SDS-PAGE. The fluorescence peak of conjugates was shifted from 328 nm to 329-338 nm, and FTIR revealed the unfolding structure of YMP. The three contact angles of COS groups increased from 65.1 degrees to 76.8 degrees with improved protein ratios, whereas CS conjugates decreased from 88.1 degrees to 81.7 degrees. The protein adsorption rate peaked was 76.4 % when the ratio of YMP:CS at 1:1. Fluorescence microscope observation revealed tightly spherical droplets, and the droplets size was from 33.8 to 177.6 mu m. All HIPEs displayed excellent thermal stability without phase separation, but freeze-thaw stability with a loss rate of 56.9 %-80.5 %. Rheological investigations demonstrated HIPEs exhibited shear-thinning behavior with solid-like properties (G'>G '') and structural recovery ability. The HIPEs complied with IDDSI Level 4-5 standards. The ratio of YMP and CS at 3:1 of HIPEs showed the resemblance to commercial mayonnaise according to the evaluations of color, extrudability, shape retention, and spread ability. The COS-based HIPEs were suitable for dispersible condiments, while CS-based HIPEs serve spreadable applications.

This study investigated the physicochemical and structural properties of octenyl succinic anhydride (OSA) rice starch esters with different degrees of substitution (DS), further examined their film properties, and established the correlation between their physicochemical properties and film properties. Fourier transform infrared spectroscopy and X-ray diffraction analysis confirmed that OSA modification primarily disrupted the amorphous regions of starch, reducing short-range order and crystallinity. These structural changes promoted starch gelatinization, as evidenced by enhanced viscosity, improved swelling capacity, and reduced gelatinization temperature and enthalpy in thermal properties. Additionally, the introduction of OSA with with larger steric hindrance increased entanglement among starch chains, inhibiting their rearrangement through hydrogen bonding. This effect minimized starch retrogradation while enhancing water retention capacity, leading to improved freeze-thaw stability and sedimentation stability. DS significantly influenced film properties, with optimal properties observed at DS = 0.019, where elongation at break and oxygen barrier properties increased by 203.22 % and 48.40 %, respectively, while solubility decreased by 19.31 %. However, the film properties were compromised at higher DS levels (0.022, 0.024). Pearson correlation analysis revealed that DS regulated film thickness, mechanical properties, and oxygen barrier properties by modulating the starch esters' viscosity, water retention capacity, and emulsification properties, thereby establishing clear relationships between the physicochemical properties of starch esters and film properties. Overall, this study reveals the influence of OSA starch esters with different DS on their film properties, promoting the precise regulation of OSA rice starch film properties for targeted applications in food packaging.

Tofacitinib citrate (TOC) is clinically used primarily for the treatment of moderate to severe rheumatoid arthritis in patients who are intolerant or inadequately responsive to methotrexate. In this study, a new polymorph of TOC (form II) was prepared using solvent crystallization. The currently marketed form I and the self-prepared form II were characterized by XRD, DSC, FT-IR, and SEM, confirming that form II is a new polymorphic form of TOC. This new polymorph was then used in the development of TOC sustained-release tablets. In the formulation design, mannitol with low hygroscopicity was used to replace sorbitol. By adding a certain amount of microcrystalline cellulose to the tablet core and maintaining the mannitol content between 60 ~ 70% of the total core weight, an in vitro dissolution behavior similar to that of the reference formulation (f2 > 50) was achieved. This indicates that replacing sorbitol with mannitol as the osmotic agent in the osmotic pump tablet core is a practical and effective method. Additionally, key preparation processes for the TOC sustained-release tablets were investigated. The results suggest that the coating weight gain of the self-prepared sustained-release tablets should be controlled between 6% and 7%, and the suitable range for laser-drilled orifice diameter is 0.55 ~ 0.90 mm.

Grapiprant (Gra), a specific antagonist of prostaglandin E2 receptors, is clinically utilized for the treatment of canine osteoarthritis (OA). As a hydrophobic small molecule drug, it is rapidly cleared from synovial fluid following intra-articular injection, which limits its anti-inflammatory therapeutic effect over extended periods. In this study, poly(lactic-co-glycolic acid) (PLGA), chitosan (CS) and hyaluronic acid (HA) were employed to formulate Gra-loaded HA/CS/PLGA@Gra nanoparticles (NPs). The HA/CS/PLGA@Gra NPs exhibited a hydrodynamic particle size of approximately 274.2nm, a narrow size distribution, a negative zeta potential of -21.5mV, and a smooth surface morphology. In vitro drug release experiments demonstrated that HA/CS/PLGA@Gra displayed sustained-release properties under both pH 7.4 and pH 5.0 conditions. In RAW264.7 macrophages, the cellular uptake of HA/CS/PLGA NPs was significantly enhanced, and they exhibited high targeting efficiency for M1-type RAW264.7 macrophages stimulated by lipopolysaccharide. Furthermore, HA/CS/PLGA@Gra can inhibit inflammation by eliminating reactive oxygen species (ROS) within cells. The hemolysis test indicated that the hemolysis rate of this compound is below 5% when the concentration of the primary drug, Grapiprant, ranges from 6.25 to 50 mu g/mL. Collectively, HA/CS/PLGA@Gra holds promise as a long-acting NPs for the treatment of -(OA) in animals.

H+, K+-ATPase, as the most critical enzyme in gastric acid secretion, has long been an attractive target for the treatment of acid-related diseases. In this study, a series of benzimidazole derivatives were designed and synthesized through conformational restriction and skeleton hopping strategies by using vonoprazan as the lead compound. Among them, compounds A12 (IC50 = 9.32 μM) and A18 (IC50 = 5.83 μM) showed better inhibition at the enzyme level. In addition, gastric acid secretion inhibition was assessed in vivo, and the results showed that A12 and A18 significantly inhibited basal gastric acid secretion, 2-deoxy-D-glucose (2DG) stimulated gastric acid secretion and histamine-stimulated gastric acid secretion. In further in vitro metabolic experiments, A12 and A18 demonstrated excellent stability and low toxicity. Pharmacokinetic studies showed that the p.o. and i.v. half-lives of A18 were 3.21 h and 8.67 ± 1.15 h, respectively. In summary, A18 might be a novel and effective potassium-competitive acid blocker, and this study provides strong support for it use in the treatment of acid-related diseases.

Biocompatible polymer microneedles (MNs) are emerging as a promising platform for transdermal drug delivery, especially for facial treatments. Therefore, an MN patch in this study uses hydrolyzed collagen (HC) contained in skin cells as the main raw material and adopts a two-step cast method to develop a rapidly dissolving microneedle (DMN) to deliver collagen in a simple and minimally invasive way, allowing the release of the encapsulated drug in the skin. By optimizing the formulation and proportion of HC and auxiliary support materials, the mechanical strength required to pierce the skin is obtained, while the soft pedestal allows for flexibility in application. The DMNs can dissolve completely in the skin within 15 min and release within ≈ 8 h, and do not cause toxicity or irritation when being applied. In contrast to the ineffectiveness of oral and external application, and the high risk of dermal injection, drug-loaded DMNs overcome the drawbacks of traditional methods with direct penetration and minimally invasive manner, enabling efficient and safe treatment. The successful preparation and research of HC DMNs have innovative and practical significance in this field, and it is expected to become a simple, effective, and popular transdermal drug delivery platform for cosmetics.

Here, the formulation of a novel bilayer tablet comprising a vitamin B6 rapid-release layer and a melatonin sustained-release layer is described. The effects of viscosity and concentration of the sustained-release matrix material, amount of diluent, and melatonin particle size on the release characteristics of melatonin were examined. In addition, the drug-release behavior of the prepared bilayer tablets was examined in different dissolution media. Further, drug-release kinetics and melatonin behavior in the sustained-release layer were evaluated based on dissolution profiles and changes in tablet weight during dissolution. Furthermore, the stability of the bilayer tablet was established. The in vitro release test revealed that vitamin B6 was completely released within 10-15 ​min, with melatonin demonstrating ∼90% cumulative release within 8 ​h. Based on kinetic model fitting results, melatonin release was well fitted to the Ritger-Peppas model; the release mechanism was non-Fick diffusion with both diffusion and erosion. The drug-release study confirmed that the melatonin sustained-release layer predominantly underwent polymer swelling rather than polymer erosion. The stability test results showed that the bilayer tablets had good stability under high temperature, high humidity, and light conditions. The bilayer tablets offer an alternative for the controlled-release oral administration of melatonin, although their in vivo effects need to be investigated in human studies.

Spinal cord injury (SCI) is a serious traumatic disease of the central nervous system, which can give rise to the loss of motor and sensory function. Due to its complex pathological mechanism, the treatment of this disease still faces a huge challenge. Hydrogels with good biocompatibility and biodegradability can well imitate the extracellular matrix in the microenvironment of spinal cord. Hydrogels have been regarded as promising SCI repair material in recent years and continuous studies have confirmed that hydrogel-based therapy can effectively eliminate inflammation and promote spinal cord repair and regeneration to improve SCI. In this review, hydrogel-based multimodal therapeutic strategies to repair SCI are provided, and a combination of hydrogel scaffolds and other therapeutic modalities are discussed, with particular emphasis on the repair mechanism of SCI.

Integrated treatment using imaging technology to monitor biological processes for the precise treatment and diagnosis of diseases to improve treatment outcomes is becoming a hot topic. Accordingly, perylene diimide (PDI) has excellent photothermal conversion and photostability, which can be used as a good material for disease treatment and diagnosis. Herein, we review the latest research progress on the real-time diagnosis of related diseases based on perylene diimide probes in the aspects of bioimaging, detection of biomarkers and determination of the pH in living cells. Furthermore, perylene diimide-based multifunctional nano-delivery systems are particularly emphasized, showing great therapeutic potential in the field of image-guided combination therapy in tumor therapy. Finally, the great opportunities and challenges still faced by perylene diimide before entering the clinic are comprehensively analyzed.

To achieve GSH-responsive 5-Fluorouridine (5-FU) delivery, a novel family of nanogel drug carriers has been successfully prepared. The new class of PAHy-based nanogels was prepared by the crossing-link reaction of poly-alpha,beta-polyasparthydrazide (PAHy) chains and 3,3'-dithiodipropionic acid (DTDPA) consisting of a redox-responsive chain network. This particle highlights recent efforts in introducing a disulfide bond to drug delivery nanogel by DTDPA, and the increased release properties of complex nanogels produced excellent glutathione (GSH)-sensitivity and significant anti-tumor therapeutic efficacy. The PAHy-based nanogels were characterized by Fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS) (nano-particle size similar to 200 nm), UV-vis spectrometry, X-ray diffraction (XRD) and differential scanning calorimetric (DSC). PAHy-based nanogels are promising controlled-release carriers for the tumor-targeting delivery of the anticancer agent 5-Fluorouridine. (C) 2016 Shenyang Pharmaceutical University. Production and hosting by Elsevier B.V.

The goal of this study was to develop a parenteral microemulsion formulation of cyclosporine A (CyA). The CyA solubility in caprylic capric triglyceride (GTCC), ethyl oleate and soybean oil were determined. The pseudo-ternary diagrams of oil (GTCC), surfactant (Solutol (R) HS-15), cosurfactants (ethanol/polyethylene glycol 400 [PEG 400] mixture) and water were constructed to identify boundaries for microemulsion existence. The CyA was added at 3, 6 and 9% w/w to the optimal microemulsion composition. Microemulsion particle size, solution viscosity and conductivity were examined. The microemulsion stability and haemolytic potential were examined after dilution in 5% dextrose solution for injection to 1 mg/mL CyA. Microemulsion stability was examined after a three-month storage at 4 and 25 degrees C. The GTCC was selected as an oil phase for CyA microemulsion based on solubility results. The optimum CyA microemulsion formulation consisted of 2.5% CyA, 9% GTCC, 24% Solutol (R) HS 15, 8% PEG 400, 4% ethanol and 52.5% water based on weight percent. The average particle sizes of the optimized blank and drug-loaded microemulsions were 68.7 nm and 71.6 nm, respectively and remained unchanged upon 25-fold dextrose dilution. The results of microemulsion physical and CyA chemical were confirmed by a three-month stability study at 4 and 25 degrees C. In vitro haemolysis studies indicated that CyA microemulsions were well tolerated by erythrocytes. The novel microemulsion formulation of CyA was developed that is suitable for parenteral administration. This new formulation could potentially have less vehicle-associated side effects that current commercial formulation of CyA based on Cremophor (R) EL and ethanol solution.

Mesoporous silica nanotubes (SNT) were synthesized using hard template carbon nanotubes (CNT) with the aid of cetyltrimethyl ammonium bromide (CTAB) in a method, which was simple and inexpensive. Scanning electron microscopy, transmission electron microscopy and specific surface area analysis were employed to characterize the morphology and structure of SNT, and the formation mechanism of SNT was also examined by Fourier transform infrared spectroscopy. There are few published reports of the mesoporous SNT with large specific surface area applied in the drug delivery systems to improve the amount of drug loading. In addition, the structure of SNT allows investigators to control the drug particle size in the pore channels and significantly increase the drug dissolution rate. The insoluble drug, cilostazol, was chosen as a model drug to be loaded into SNT and we developed a simple and efficient method for regulating the drug release by using a gelatin coating with different thicknesses around the SNT. The release rate was adjusted by the amount of gelatin surrounding the SNT, with an increased barrier leading to a reduction in the release rate. A model developed on the basis of the Weibull modulus was established to fit the release results. (C) 2015 Elsevier B.V. All rights reserved.

The purpose of this study was to prepare and characterize nanoporous silica@poly(ethyleneimine)s (NS@P) xerogel and methanol modified NS@P xerogel synthesized with biomimetic method, and investigate controlled release behavior of propranolol hydrochloride (PNH) loaded carrier materials in vitro and in vivo. Preparation was conducted at ambient conditions, and NS@P xerogel as well as PNH loaded NS@P xerogel were characterized using Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and differential scanning calorimeter (DSC). Investigations on morphology and porous characteristics of NS@P xerogel and methanol modified NS@P xerogel were evaluated with scanning electron microscopy (SEM), transmission electron microscopy (TEM) and nitrogen adsorption. The results showed that the order of morphology compactness was NS@P xerogel > 25%NS@P xerogel > 75%NS@P xerogel because PEIs scaffold ability for silica condensation and forming hydrogen bond weakened with increasing volume ratio of methanol modification. Moreover, SBET decreased and uniformity of pore size distribution was interrupted after methanol modification. PNH loaded carrier materials displayed controlled release, and release effect was related with pore size of materials and PEIs scaffold ability. In vivo pharmacokinetic study demonstrated that release of PNH was delayed due to the PNH incorporated inside carrier materials and controlled release effect was in accordance with in vitro results.

Background: The cubic (Q(II)) phase is a promising sustained-release system. However, its rigid gel-like propensity is highly viscous, which makes it difficult to handle in pharmaceutical applications. To circumvent this problem, a less viscous lamellar (L-alpha) phase that could spontaneously transform to Q(II) phase by the introduction of water or biological artificial fluid can be used. However, the kinetics pathway of phase transition, susceptibility to digestive processes and impact of the transition on drug release are not yet well understood.Method: We investigated various biological artificial fluid-induced L-alpha to inverse Q(II) phase transition over time in glyceryl monooleate (GMO) by water penetration scan and light polarizing microscopy. To reveal the structure stability, fluorescence spectroscopy studies were conducted using pyrene as a probe. Furthermore, the release mechanism of pyrene as a lipophilic drug model in the spontaneously formed Q(II) was investigated.Result: Although hexagonal (H-II) mesophases occurred when phosphate buffered saline (PBS) 7.4, 0.1 M HCl or sodium taurocholate (NaTC) solutions were introduced to GMO at room temperature, they disappear with the exception of 0.1 M HCl at 37 degrees C. Compared with 25 degrees C, L alpha to Q(II) phase transition was in a faster rate as almost completely transforms were observed after 2 h post-immersion. The spontaneously formed mesophases were stable over 24 h immersions in PBS or pancreatic lipase solutions as proven by the extremely low fluorescence signal, however they were digestible by bile salts. This result indicated that digestion by bile salts was the major pathway instead of digestion by lipases. Moreover, pyrene fluorescence spectroscopy confirmed that the digestion by bile salts induced the formation of GMO-bile salt mixed micelles whose performance depended on the bile salt concentrations. This dependence influenced the drug release from the spontaneously formed Q(II) phase.Conclusion: All the results concluded that temperature, pH and ionic strength tendencies for the formation of non-lamellar structures greatly influenced the self-assembly process, thereby affecting the final mesophase structure. The results of this study are important to understand the lamellar to non-lamellar lipid-phase transitions and their possible pharmaceutical applications.

The purpose of this study was to evaluate the feasibility of ion-exchange fiber ZB-1 as a novel carrier in oral taste-masked mucoadhesive sustained-release suspensions. Propranolol (PPN) hydrochloride was selected as a model drug with good water solubility, short half life and bitter taste. The PPN-fiber complexes (PF) were prepared by a batch process and coated with Eudragit(®) RS100. Gamma scintigraphy was performed on fasted volunteers revealed about 30% ZB-1 and more than 50% coated ZB-1 were still remaining in the stomach at 6h. In vitro results showed the releases of PF and coated PPN-fiber complexes (C-PF) were sustained. The release, drug content and particle size of C-PF were influenced by coat to core ratio, concentration of coating material and rotation rate. The suspension was stable after standing for 30 days in 0.5% Carbopol(®) with no release rate and taste changed. The administration of C-PF suspension to rats resulted a significant different (P<0.05) improvement of the plasma drug level and prolongation of the release. However, because of the burst effect, the Cmax values of PF suspension didn't differ from drug solution (P>0.05). Furthermore, a linear relationship between in vitro dissolution and in vivo absorption was observed.

Ion-exchange fibers were different from conventional ion-exchange resins in their non-cross-linked structure. The exchange was located on the surface of the framework, and the transport resistance reduced significantly, which might mean that the exchange is controlled by an ionic reaction instead of diffusion. Therefore, this work aimed to investigate the load and release characteristics of five model drugs with the strong cationic ion-exchange fiber ZB-1. Drugs were loaded using a batch process and released in United States Pharmacopoeia (USP) dissolution apparatus 2. Opposing exchange kinetics, suitable for the special structure of the fiber, were developed for describing the exchange process with the help of thermodynamics, which illustrated that the load was controlled by an ionic reaction. The molecular weight was the most important factor to influence the drug load and release rate. Strong alkalinity and rings in the molecular structures made the affinity between the drug and fiber strong, while logP did not cause any profound differences. The drug-fiber complexes exhibited sustained release. Different kinds and concentrations of counter ions or different amounts of drug-fiber complexes in the release medium affected the release behavior, while the pH value was independent of it. The groundwork for in-depth exploration and further application of ion-exchange fibers has been laid.