Continuous Release Research Articles

A Multifunctional Hydrogel Fabricated by Direct Self-Assembly of Natural Herbal Small Molecule Mangiferin for Treating Diabetic Wounds.

Clinical studies have continually referred to the involvement of drug carrier having dramatic negative influences on the biocompatibility, biodegradability, and loading efficacy of hydrogel. To overcome this deficiency, researchers have proposed to directly self-assemble natural herbal small molecules into a hydrogel without any structural modification. However, it is still a formidable challenge due to the high requirements on the structure of natural molecules, leading to a rarity of this type of hydrogel. Mangiferin (MF) is a natural polyphenol of C-glucoside xanthone with various positive health benefits, including the treatment of diabetic wounds, but its poor hydrosolubility and low bioavailability significantly restrict the clinical application. Inspired by these, with heating/cooling treatment, a carrier-free hydrogel (MF-gel) is developed by assembling the natural herbal molecule mangiferin, which is mainly governed through hydrogen bonds and intermolecular π-π stacking interactions. The as-prepared hydrogel has injectable and self-healing properties and shows excellent biocompatibility, continuous release ability, and reversible stimuli-responsive performances. All of the superiorities enable the MF-based hydrogel to serve as a potential wound dressing for treating diabetic wounds, which was further confirmed by both the vitro and vivo studies. In vitro, the MF-gel could promote the migration of healing-related cells from peripheral as well as the angiogenesis and displays the capacity of mediating inflammation response by scavenging the intracellular ROS. In vivo, the MF-gel accelerates wound contraction and healing via inflammatory adjustment, collagen deposition, and angiogenesis. This study provides a facile and effective method for diabetic wound management and emphasizes the direct self-assembly hydrogel from natural herbal small molecule.

Thermal conductivity of MX80 powders-granules mixture and its prediction for high-level radioactive waste repository

Bentonite granules and their mixtures with powders are considered to be a preferred sealing material for filling gaps between buffer layer and surrounding rock in high-level radioactive waste (HLW) repository. Due to continuous release of decay heat from nuclides, thermal conductivity of bentonite granules must be assessed. In this study, the effects of water content, dry density, temperature on the thermal conductivity in the directions parallel (λpar) and perpendicular (λperp) to the bedding plane of MX80 powders-granules mixture (PGM) were investigated by thermal probe technique. Test results showed that the thermal conductivity of powdered bentonite (PB) was higher than that of PGM and λpar was higher than λperp. With increasing water content, the difference rate (δPSD) in thermal conductivity between PB and PGM increased, and anisotropy coefficient α (a ratio of λpar to λperp) decreased, while the effects of dry density and temperature on δPSD and α were not obvious. The factor importance was analyzed, and results showed that the effects of water content, dry density, temperature, and particle size distribution decreased successively. A modified geometric mean (MGM) model for predicting thermal conductivity of PGM with temperature is proposed and it predicted thermal conductivity of MX80 PGM well.

Urea-Loaded Core–Shell MOF/Silica Nanocarriers for Continuous Nitrogen Release to Crops

Urea-Loaded Core–Shell MOF/Silica Nanocarriers for Continuous Nitrogen Release to Crops

Novel pH-responsive hybrid hydrogels for controlled delivery of curcumin: Overcoming conventional constraints and enhancing cytotoxicity in MCF-7 cells

Traditional drug delivery techniques often have drawbacks such inadequate bioavailability, quick clearance, and non-specific targeting, which may result in unfavorable side effects. Hybrid nanocarriers composed of nanoclay have the potential to be a viable solution to these problems. The goal of this work was to design a biocompatible hybrid nanocarrier that would release curcumin under regulated conditions to specific locations, especially cancer cells. FTIR, XRD, and FESEM were used to effectively construct and evaluate our polyvinyl pyrrolidone/polyethylene glycol/montmorillonite (PVP/PEG/MMT) hybrid hydrogels, verifying their synthesis and intended features. Zeta potential and DLS studies showed a suitable size distribution (∼300 nm) and high stability. The curcumin encapsulation efficiency and release profile were assessed using the use of UV spectrophotometry and the dialysis bag technique. The findings showed a gradual and continuous release that was highly impacted by the acidic environment (which mimicked the characteristics of cancer cells), suggesting pH-responsive activity. The MTT test was used in vitro cytotoxicity experiments to show that curcumin-loaded nanocarriers were more effective against MCF-7 cancer cells than curcumin in solution. Increased rates of necrosis and apoptosis in cancer cells treated with the nanocarrier formulation were further validated by flowcytometry. According to these results, PVP/PEG/MMT hybrid hydrogels have a lot of potential as a cutting-edge drug delivery strategy for curcumin. They may be able to overcome some of the drawbacks of traditional techniques and improve the effectiveness of treatment against cancer cells.

Mitigating autogenous shrinkage of cement with carbon nanotube sponge

Autogenous shrinkage can be mitigated by the addition of superabsorbent polymer (SAP), however, typically at the cost of a significant strength loss. To overcome such dilemma, hydrophilic carbon nanotube sponge (H-CNTSP) was proposed in this study as a novel internal curing agent. Due to the high porosity and enriched hydrophilic functional groups, H-CNTSP can absorb pore solution at 72 g/g driven by the capillary force, which is 176%–620 % higher than the commercial SAPs. The autogenous shrinkage of cement can be reduced or mitigated with the addition of 0.05–0.2 wt% H-CNTSP due to the continuous water release after final setting. Interestingly, the compressive strength loss resulting from the addition of H-CNTSP can be greatly diminished and even be overcompensated by the formation of CNT/hydrate nanocomposite shell with a higher modulus. This study illustrates the great potential to optimize concrete performance through proper design of assembly structures with chemically functionalized nanomaterials.

Mg-gallate metal-organic framework-based sprayable hydrogel for continuously regulating oxidative stress microenvironment and promoting neurovascular network reconstruction in diabetic wounds

Chronic diabetic wounds are the most common complication for diabetic patients. Due to high oxidative stress levels affecting the entire healing process, treating diabetic wounds remains a challenge. Here, we present a strategy for continuously regulating oxidative stress microenvironment by the catalyst-like magnesium-gallate metal-organic framework (Mg-GA MOF) and developing sprayable hydrogel dressing with sodium alginate/chitosan quaternary ammonium salts to treat diabetic wounds. Chitosan quaternary ammonium salts with antibacterial properties can prevent bacterial infection. The continuous release of gallic acid (GA) effectively eliminates reactive oxygen species (ROS), reduces oxidative stress, and accelerates the polarization of M1-type macrophages to M2-type, shortening the transition between inflammation and proliferative phase and maintaining redox balance. Besides, magnesium ions adjuvant therapy promotes vascular regeneration and neuronal formation by activating the expression of vascular-associated genes. Sprayable hydrogel dressings with antibacterial, antioxidant, and inflammatory regulation rapidly repair diabetic wounds by promoting neurovascular network reconstruction and accelerating re-epithelialization and collagen deposition. This study confirms the feasibility of catalyst-like MOF-contained sprayable hydrogel to regulate the microenvironment continuously and provides guidance for developing the next generation of non-drug diabetes dressings.

Nonenzymatic electrochemical approaches for promethazine monitoring in aquatic media

Promethazine hydrochloride (PMH) is a phenothiazine derivative extensively utilized in healthcare settings. Its excessive consumption and continuous release into environmental water bodies can lead to adverse effects on human health and disrupt the equilibrium of aquatic ecosystems. Therefore, monitoring PMH levels is essential to maintain therapeutic efficacy and safeguard the well-being of both humans and aquatic life. This study encompasses the synthesis of samarium tungstate nanorods (SmWO) via hydrothermal method, followed by their incorporation into a composite with sulfur-doped graphitic carbon nitride (SmWO/SGCN) using ultrasonication technique. The morphology and physicochemical properties of the synthesized composite were thoroughly examined using various analytical methods. Subsequently, the electrocatalytic activity of the developed sensor was assessed for sensing PMH via voltammetry techniques. Under optimized conditions, the fabricated electrode exhibited an 8.1 nM detection limit with a wide linear range (0.02–199 µM), and high sensitivity (2.349 µA µM−1 cm−2) for PMH detection. The suggested SmWO/SGCN composite electrode shows promising practical potential for detecting PMH in environmental aquatic samples.

Gelatin/heparin coated bio-inspired polyurethane composite fibers to construct small-caliber artificial blood vessel grafts

Long-term patency and ability for revascularization remain challenges for small-caliber blood vessel grafts to treat cardiovascular diseases clinically. Here, a gelatin/heparin coated bio-inspired polyurethane composite fibers-based artificial blood vessel with continuous release of NO and biopeptides to regulate vascular tissue repair and maintain long-term patency is fabricated. A biodegradable polyurethane elastomer that can catalyze S-nitrosothiols in the blood to release NO is synthesized (NPU). Then, the NPU core-shell structured nanofiber grafts with requisite mechanical properties and biopeptide release for inflammation manipulation are fabricated by electrospinning and lyophilization. Finally, the surface of tubular NPU nanofiber grafts is coated with heparin/gelatin and crosslinked with glutaraldehyde to obtain small-caliber artificial blood vessels (ABVs) with the ability of vascular revascularization. We demonstrate that artificial blood vessel grafts promote the growth of endothelial cells but inhibit the growth of smooth muscle cells by the continuous release of NO; vascular grafts can regulate inflammatory balance for vascular tissue remodel without excessive collagen deposition through the release of biological peptides. Vascular grafts prevent thrombus and vascular stenosis to obtain long-term patency. Hence, our work paves a new way to develop small-caliber artificial blood vessel grafts that can maintain long-term patency in vivo and remodel vascular tissue successfully.

Self-Lubricating, Living Contact Lenses.

The increasing prevalence of dry eye syndrome in aging and digital societies compromises long-term contact lens (CL) wear and forces users to regular eye drop instillation to alleviate discomfort. Here a novel approach with the potential to improve and extend the lubrication properties of CLs is presented. This is achieved by embedding lubricant-secreting biofactories within the CL material. The self-replenishable reservoirs autonomously produce and release hyaluronic acid (HA), a natural lubrication and wetting agent, long term. The hydrogel matrix regulates the growth of the biofactories and the HA production, and allows the diffusion of nutrients and HA for at least 3 weeks. The continuous release of HA sustainably reduces the friction coefficient of the CL surface. A self-lubricating CL prototype is presented, where the functional biofactories are contained in a functional ring at the lens periphery, outside of the vision area. The device is cytocompatible and fulfils physicochemical requirements of commercial CLs. The fabrication process is compatible with current manufacturing processes of CLs for vision correction. It is envisioned that the durable-by-design approach in living CL could enable long-term wear comfort for CL users and minimize the need for lubricating eye drops.

Microencapsulation of Annona muricata L. seed extract for the control of Plutella xylostella

Insecticidal plants have stood out in Integrated Pest Management (IPM), associated with other control strategies, and therefore, the development of microencapsulated formulations, which make the active ingredient protected with slow and continuous release, becomes necessary. Thus, the present study aimed to develop, characterize and evaluate the lethal effect of the Microencapsulated Ethanolic Extract (MEE) from Annona muricata L. (Annonaceae) seeds on Plutella xylostella. MEE was developed in a B-290 BUCHI Mini Spray Dryer, using polymers starch, maltodextrin, gelatin and aerosil, and characterization was carried out through microparticle size and humidity, polydispersity index, morphologic analysis, Thermogravimetric analysis (TGA) and scanning electron microscope (SEM). MEE presented particle distribution with evident bimodal behavior, with diameters from 0.48 to 79.43 μm and polydispersity index equal to 6.414. Through SEM analysis, microparticles presented spherical and irregular shape, with smooth and rough/wavy, continuous, homogeneous surface, with variable size and external surface continuous in walls, with no apparent cracks. TGA demonstrated 5 decomposition stages, similar to the ethanolic extract. The estimated Lethal Concentrations (LC) for the ethanolic extract and MEE were: LC50 and CL99 of 0.204 and 5.675 g/L and 0.114 and 4.166 g/L, respectively. It could be concluded that the development of MEE was effective using the spray dryer method, with uniform microcapsules with insecticidal action able to be more soluble and persist the action of the active ingredient for longer times, improving its application in the field.

Investigation on a mobile fire extinguishing approach using liquid carbon dioxide as inert medium for underground mine.

Injecting carbon dioxide is the most effective means of preventing and extinguishing fires in sealing hazardous areas, but the traditional method slowly and remotely injects carbon dioxide gas into the well after gasification on the ground, which is dependent on the complete mine pipe network without cooling effect. To inject liquid directly from the tank with vacuum interlayer and heat insulating powder for rapid inerting and cooling, a new approach using track mobile platform to go deep into the underground mine disaster area is proposed, so the liquid can be delivered to the nozzle at the end of DN40 large diameter pipe, and the continuous gasification jet can be realized. The experimental results show that: (1) The liquid volume in a tank of vacuum degree within 2.0 Pa and 200 mm interlayer reduced no more than 15.5% after 48 days; (2) Taking the pressure in the tank as the power source, because of environmental differences inside and outside the pipe after 100 m pressure holding delivery, the physical form of liquid and gas could be converted instantly; (3) The continuous discharge time without ice blocking for a tank full of 2 m3 liquid was about 10.5 min under 25 L dual mode nitrogen pressurization, which is 1/12 of injection time after ground gasification; (4) Based on the temperature decrease trend measured at different positions, the cooling characteristics on liquid gasification jet path are quantified, and the calculation formula of temperature changing with time on the center line of liquid gasification jet is obtained. Through this new approach, the integration of vacuum insulated storage, safe mobile transportation, and continuous and rapid release with large flow can be achieved for the liquid carbon dioxide.

Structure and replication cycle of a virus infecting climate-modulating alga Emiliania huxleyi.

The globally distributed marine alga Emiliania huxleyi has cooling effect on the Earth's climate. The population density of E. huxleyi is restricted by Nucleocytoviricota viruses, including E. huxleyi virus 201 (EhV-201). Despite the impact of E. huxleyi viruses on the climate, there is limited information about their structure and replication. Here, we show that the dsDNA genome inside the EhV-201 virion is protected by an inner membrane, capsid, and outer membrane. EhV-201 virions infect E. huxleyi by using fivefold vertices to bind to and fuse the virus' inner membrane with the cell plasma membrane. Progeny virions assemble in the cytoplasm at the surface of endoplasmic reticulum-derived membrane segments. Genome packaging initiates synchronously with the capsid assembly and completes through an aperture in the forming capsid. The genome-filled capsids acquire an outer membrane by budding into intracellular vesicles. EhV-201 infection induces a loss of surface protective layers from E. huxleyi cells, which enables the continuous release of virions by exocytosis.

Enhancing selegiline hydrochloride efficacy: Box Behnken-optimized liposomal delivery via intranasal route for Parkinson’s disease intervention

The clinical use of selegiline hydrochloride in conventional dosage forms is to reduce the progression of Parkinson’s disease (PD). However, its limited access to the brain, short half-life, and first-pass metabolism minimize brain uptake. Nano-based liposomes offer promising tools for brain-targeted delivery of therapeutics, especially intranasally administered cationic liposomes that target the brain region via the olfactory route and reduce biodistribution. In the present work, cationic liposomes encapsulated with selegiline hydrochloride were fabricated for intranasal administration against PD. The liposomes were initially optimized by Box Behnken design, and the selected run was coated with stearylamine to provide a cationic charge to the liposomes. The final coated liposomes, SH-LP3, demonstrated a minimum size of 173 ± 2.13 nm, an ideal zeta potential of +16 ± 1.98, and achieved a maximum entrapment efficiency of 40.14 ± 1.83%. Morphology analysis showed the spherical shape of liposomes in the size range of 100–200 nm. The in vitro cytotoxicity assay in SHSY5Y cell lines showed a significant decrease in toxicity, almost ten times less, compared to pure selegiline hydrochloride. Animal studies on rotenone-lesioned C57BL6 mice model for PD were performed to investigate the effect of intranasally administered liposomes. The SH-LP3 formulation exhibited remarkable effectiveness in relieving symptoms of PD. This extensive analysis emphasizes the possibility of intranasally administered SH-LP3 liposomes as a feasible treatment option for PD. The formulation not only delivers continuous drug release but also displays better safety and efficacy, providing a platform for additional studies and growth in the domain of PD treatment.

Photocatalytic Activity and Antibacterial Properties of ZnO/CNTs Composites

Photocatalytic technology is one of the promising technologies for wastewater treatment. Herein, zinc oxide/multi-walled carbon nanotubes (ZnO/CNTs) photocatalyst was successfully prepared by hydrothermal method with combining in-situ synthesis technology. The micro-morphology, crystalline structure, surface chemical elements, and optical properties were characterized by SEM, TEM, XRD, FTIR, UV-Vis, and DRS technologies. The ZnO/CNTs photo-catalyst exhibited enhancement photo activity for degradation of organic pollutants under simulated light irradiation. Specifically, the photo-catalytic activity of the ZnO/CNTs catalysts improved with the rise of CNTs content in the composites. Investigation on the photo-degradation mechanism verified that the presence of CNTs in the catalyst not only optimized the band structure of ZnO semiconductor but also contributed to the transfer of photo-generated electrons and reducing the recombination of electron-hole pairs due to its excellent conductivity. Moreover, the active radical groups such as superoxide radical (O-2), hole (h+), and hydroxyl radical (·OH) played the dominated role for the pollutants degradation under the simulated sunlight irradiation. In addition, ZCT20 catalysts and light irradiation had synergistic effects on antibacterial activity, whose antibacterial rates against E. coli and S. aureus were up to 99.96% and 99.94%, respectively. Investigation on antibacterial mechanisms revealed that the existence of ROS and the continuous release of Zn2+ played an important role for improving the antibacterial activity of the ZCT20 catalyst under the simulated sunlight irradiation.

Revealing nitrate uptake and dispersion dynamics using high-frequency sensors and two-dimensional modeling in a large river system

Nitrate pollution of water bodies is a critical issue in many parts of the world because of its negative effects on aquatic ecosystem and human health. Effective management of pollution, such as the continuous or instantaneous release from point-sources, requires an understanding – with high spatial and temporal resolution – of how nitrate is dispersed and cycled within rivers. Nitrate sensing data show promise for this purpose, but their integration into numerical models is scarce; thus, questions remain regarding the necessary spatial grid size and temporal resolution required to resolve sensor readings. In this study, we developed an unsteady two-dimensional model to simulate nitrate transport, dispersal, and cycling along a 33-km stretch of the Kansas River (USA), following a strategic release of nitrogen from a decommissioned fertilizer plant. To validate modeled estimates of dispersion and uptake, we integrated 15-minute nitrate and temperature data from two aquatic sensors, one located proximal to the fertilizer release point and a second further downstream after complete lateral mixing. Model results at the site near to the contamination (0.4 km) were highly sensitive to river grid size and turbulent mixing, but insensitive to uptake. Results at the site far downstream of the contamination (31 km) were unaffected by grid size or mixing parameterization but were very sensitive to selection of uptake rate. High-frequency sensors allowed us to resolve diel variability in nitrate signals, which we incorporated into the model to improve performance and model realism. The 33-km study reach assimilated 14% of the total nitrate load in the river, or approximately half of what was contributed by the fertilizer release, during the two-month study period. Regarding nitrate cycling, modeled Cdiel/Cmax ranged from 0.04 to 0.11 whereas sensor observations showed much higher Cdiel/Cmax values of 0.11 to 0.25. Disagreements between data observations and model simulations in cycling are hypothesized to exist due to potential breakdown of the first-order rate kinetics. Together, our study shows the potential of combining numerical models and high-frequency data for a better understanding of the physical and biogeochemical processes that control nitrate dynamics in aquatic environments.

Synthesis and Characterization of Cassava Gum Hydrogel Associated with Chlorhexidine and Evaluation of Release and Antimicrobial Activity.

Hydrogels from natural sources are attracting increasing interest due to their ability to protect biologically active molecules. Starch extracted from cassava tubers is a promising material for synthesizing these hydrogels. Copolymerization of cassava gum and incorporation of chlorhexidine digluconate (CLX) into the hydrogels is confirmed by changes in the crystallographic profile, as observed through X-ray diffraction, and a shift in the 1000 cm-1 band in the Fourier-transform infrared spectroscopy spectrum. The differential scanning calorimetry reveals changes in the decomposition temperature of the synthesized hydrogels related to CLX volatility. Micrographs illustrate the material's porosity. Release tests indicate a constant linear release over 72 h, while antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans is satisfactory, with 100% effectiveness from 0.5% CLX and the formation of inhibition halos. Toxicity and biocompatibility studies show no cytotoxicity. The continuous release of chlorhexidine is promising for components of biomedical implants and applications as it can ensure antimicrobial action according to specific therapeutic needs.

Chemoselective Synthesis and Anti-Kinetoplastidal Properties of 2,6-Diaryl-4H-tetrahydro-thiopyran-4-one S-Oxides: Their Interplay in a Cascade of Redox Reactions from Diarylideneacetones.

2,6-Diaryl-4H-tetrahydro-thiopyran-4-ones and corresponding sulfoxide and sulfone derivatives were designed to lower the major toxicity of their parent anti-kinetoplatidal diarylideneacetones through a prodrug effect. Novel diastereoselective methodologies were developed and generalized from diarylideneacetones and 2,6-diaryl-4H-tetrahydro-thiopyran-4-ones to allow the introduction of a wide substitution profile and to prepare the related S-oxides. The in vitro biological activity and selectivity of diarylideneacetones, 2,6-diaryl-4H-tetrahydro-thiopyran-4-ones, and their S-sulfoxide and sulfone metabolites were evaluated against Trypanosoma brucei brucei, Trypanosoma cruzi, and various Leishmania species in comparison with their cytotoxicity against human fibroblasts hMRC-5. The data revealed that the sulfides, sulfoxides, and sulfones, in which the Michael acceptor sites are temporarily masked, are less toxic against mammal cells while the anti-trypanosomal potency was maintained against T. b. brucei, T. cruzi, L. infantum, and L. donovani, thus confirming the validity of the prodrug strategy. The mechanism of action is proposed to be due to the involvement of diarylideneacetones in cascades of redox reactions involving the trypanothione system. After Michael addition of the dithiol to the double bonds, resulting in an elongated polymer, the latter-upon S-oxidation, followed by syn-eliminations-fragments, under continuous release of reactive oxygen species and sulfenic/sulfonic species, causing the death of the trypanosomal parasites in the micromolar or submicromolar range with high selectivity indexes.

Intranasal delivery of phenytoin loaded layered double hydroxide nanoparticles improves therapeutic effect on epileptic seizures

Improving the efficiency of antiseizure medication entering the brain is the key to reducing its peripheral toxicity. A combination of intranasal administration and nanomedicine presents a practical approach for treating epileptic seizures via bypassing the blood-brain barrier. In this study, phenytoin (PHT) loaded layered double hydroxide nanoparticles (BSA-LDHs-PHT) were fabricated via a coprecipitation − hydrothermal method for epileptic seizure control. In this study, we expound on the preparation method and characterization of BSA-LDHs-PHT. In-vitro drug release experiment shows both rapid and continuous drug release from BSA-LDHs-PHT, which is crucial for acute seizure control and chronic epilepsy therapy. In-vivo biodistribution assays after intranasal administration indicate excellent brain targeting ability of BSA-LDHs. Compared to BSA-Cyanine5.5, BSA-LDHs-Cyanine5.5 were associated with a higher brain/peripheral ratio across all tested time points. Following intranasal delivery with small doses of BSA-LDHs-PHT, the latency of seizures in the pentylenetetrazole-induced mouse models was effectively improved. Collectively, the present study successfully designed and applied BSA-LDHs-PHT as a promising strategy for treating epileptic seizures with an enhanced therapeutic effect.

Transdermal diffusion research on functional substances of Jingu Zhitong Gel

This study systematically explored the transdermal diffusion law of functional substances of Jingu Zhitong Gel(JGZTG). The transdermal diffusion research methods of JGZTG were investigated by single factor trial with the automated transdermal(dry-heat) sampling system. High performance liquid chromatography(HPLC) content determination method was established to determine the contents of ferulic acid, senkyunolide I, cinnamic acid, hydroxy-ε-xanthoxylin, hydroxy-α-xanthoxylin, and hydroxy-β-xanthoxylin in the transdermal diffusion solution of JGZTG. The transdermal diffusion law of the components within 16 h was investigated. The results showed that the optimal transdermal diffusion method of JGZTG was as follows: Rat skin was used as the transdermal barrier; normal saline was used as the receiving medium; the dosage of JGZTG was 0.3 g, and the receiving solution was extracted by ethyl acetate. The results of transdermal diffusion showed that the release of ferulic acid, cinnamic acid, and senkyunolide I increased significantly at 0-8 h and slowed down at 8-16 h. The drug release was a synergic process of diffusion and dissolution, in which ferulic acid and cinnamic acid followed Higuchi and Ritger-Peppas equations, and liguolactone I followed Higuchi equation. The transdermal diffusion curves of hydroxy-ε-zanthoxylin, hydroxy-α-zanthoxylin, and hydroxy-β-zanthoxylin showed continuous release within 16 h, and the drug release was skeleton dissolution. The diffusion law followed zero-order equation, first-order equation, and Ritger-Peppas equation. In clonclusion, it is a controlled release of ferulic acid, ligustrone I, cinnamic acid, hydroxy-ε-pyrroxylin, hydroxy-α-pyrroxylin, and hydroxy-β-pyrroxylin in JGZTG, which can maintain stable blood drug concentration with 16 h, and the cumulative transmittance of each component with 12 h can reach 80% of cumulative transmittance with 24 h, which is in line with the clinical drug use law of bis in die.

Methotrexate-Polymer Nanocomposites for Targeted Pulmonary Drug Delivery

Nanocomposite formulation is a suitable technology that enables the development of successful dry powder inhalers. The methotrexate (MTX) and polyamide-disulfide (polymer) were used as a model to form MTX-polymer nanocomposites. Different amounts of the independent variable, MTX (0.025 and 0.050 g), polymer (0.05 and 0.01 g), pH (6.7 and 11.3), and across-linker ferric chloride (FeCl3) (0.05 and 0.10 g) were used. The loading efficiency and particle size were dependent variables. The optimized formula can be obtained with the highest loading efficiency and optimum particle size. This formula can be collected by using 0.025 g of drug, 0.079 g of polymer, 0.050 g of FeCl3, and pH = 6.7. The release of MTX from the nanocomposites occurs in two release steps; the first release step starts from the beginning up to 60 min, followed by a continuous release phase within 60 min. The results of the NGI analysis demonstrated that 28.1% of the nominated dose in each puff reached the lower parts of the respiratory system, an indication that the nanocomposites can be used in the delivery of MTX as a respiratory system.