Sustained Release Effect Research Articles

D-Mannose-Decorated Chitosan Nanoparticles for Enhanced Targeting of 5-Fluorouracil in the Therapy of Colon Cancer

Colorectal cancer is one of the most familiar malignant tumor, which requires an efficient system specially fabricated for targeted delivery of anticancer agents. 5-Fluorouracil (5-FU) is mostly used as an antineoplastic agent in gastrointestinal cancer. Ligand-based targeting approaches increase the internalization of NPs within resistant cells, which results in highly well-organized treatment, markedly reduces systemic toxicities, and minimize collateral damage to adjacent healthy cells. Mannose-conjugation was carried out to increase its uptake by the cancer cells through receptor-mediated endocytosis. It was attempted to develop d-mannose conjugated 5-fluorouracil (5-FU) entrapped nanoparticles (NPs) with an objective to target colon cancer. The conjugated-NPs were characterized for distinct parameters, for instance, pH, viscosity, morphology of particles, particle size (PS), size-distribution, polydispersity index, %yield, surface charge, and entrapment efficiency. However, formulations were also examined (in vitro) for cell cytotoxicity against CT26 and drug leakage in dissolution fluid. The fabricated NPs produced sustained drug release effect and exhibited release of 5-FU for 24 h. In addition, conjugation of d-mannose with NPs significantly augmented sustained effect over non-conjugated formulations. The preliminary results obtained for this study suggested that conjugation of d-mannose with chitosan NPs augmented the targeting effect in colon cancer. In conclusion, d-mannose conjugated NPs proved to be a more efficient carrier system over other conventional formulation as a delivery system for tumor.

Antioxidant and multi-sensitive PNIPAAm/keratin double network gels for self-stripping wound dressing application.

Hydrogel is a potential wound dressing material due to its ability to maintain a humid environment, the strong absorptive capacity of exuded tissue fluid, and gas exchange function. Herein, poly(N-isopropyl acrylamide)/keratin double network (PNIPAAm/keratin DN) gels were fabricated through covalent and ionic double cross-linking strategy. The effects of PNIPAAm/keratin ratios on the morphology and swelling rate of gels were characterized. The DN gels could swell up from 2600% to 4600% in proportion to the keratin content, demonstrating their great ability to absorb tissue fluid. The gels possessed thermo-sensitiveness, imparting self-stripping property. Moreover, the antibacterial chlorhexidine acetate (CHX) was loaded into gels with a post-fabrication drug-loading strategy. The release behavior showed that CHX-loaded DN gels exhibited multiple responsive characteristics (temperature, pH, and ROS). Furthermore, the drug-loaded gels showed greater antibacterial activity than free CHX due to the sustained drug release effect. Meanwhile, the antioxidant efficiency of PNIPAAm/keratin DN gels was ca. 33.1%, while the PNIPAAm gel was just ca. 18.2%, indicating the strong oxidation resistance of DN gels. In the Sprague Dawley (SD) rat skin defect model, the hydrogel had better tissue regeneration ability than the commercial film. Taken together, the multifunctional PNIPAAm/keratin DN gels are potential candidates for clinical wound treatment.

Effect of quaternary ammonium salt-loaded nanometre mesoporous calcium-silica particle biomaterials on human exercise health

This paper uses human gingival fibroblasts to test the cytotoxicity of [email protected] to determine the appropriate antibacterial concentration. The cell proliferation activity detection kit will be used to evaluate the effect of the material and the cells on the cell proliferation activity within 1 week. Furthermore, Escherichia coli, Staphylococcus aureus and Prohormones gingivitis will be used to form a plaque biofilm containing a single flora, and the obtained plaque biofilm will be used to treat the grafted Quaternary ammonium compounds (QAC) on [email protected] and the released antibacterial effect of effective concentration of metronidazole was evaluated. The antibacterial results will be stained with fluorescent dead and live bacteria dyes to observe the biofilm status under a laser confocal scanning electron microscope, and use the colony counting method and bacterial viability test XTT reagent for quantitative evaluation. Metronidazole-loaded quaternary ammonium salt modified hollow mesoporous silica [email protected] synthesised by self-template method has a stable mesoporous structure and sustained metronidazole release effect, showing good biocompatibility and antibacterial ability.

DOX-Loaded Gelatin Composite Hydrogels with Oxidation-Triggered Drug Release Property

Hydrogels developed as stimuli-responsive drug delivery systems (DDSs) are increasingly concerned research focus in many fields such as chemistry, functional materials and biomedicine. Herein, we report the fabrication, characterization and drug release property of new gelatin composite hydrogels by using biocompatible gelatin and the doxorubicin (DOX)-loaded micelles of a redox-responsive side-chain ferrocene (Fc)-containing amphiphilic diblock copolymer PNFc-b-PNTEG (Fig. 1). The self-assembly method was firstly adopted to prepare the DOX-loaded micelles of PNFc-b-PNTEG with oxidation-sensitive release property, and the DOX-loaded gelatin composite hydrogels were then successfully fabricated by using blending and soaking methods, respectively. The formed hydrogels were characterized by many techniques including scanning electron microscope, energy-dispersive spectroscopy, differential scanning calorimetry, thermogravimetry and swelling test. The successful encapsulation of the DOX-containing micelles in the gelatin matrix was demonstrated, and the prepared composite hydrogels exhibited improved thermal stability, faster swelling speed and higher swelling ratios. The oxidation-triggered controlled in vitro release of DOX from the composite hydrogels was confirmed by using FeCl3 at different concentrations as an oxidizing agent. The composite hydrogels could act as excellent solid carriers to guarantee the sustained-release effect of DOX, and it is feasible to keep the DOX molecules with high concentration at the specific site for a long period (20 days or so). Thus, the present composite hydrogels are anticipated to be good candidates as redox-responsive DDSs.

Wettability and contact angle affect precorneal retention and pharmacodynamic behavior of microspheres

In the present study, we describe the development of betaxolol hydrochloride and montmorillonite with ion exchange in a single formulation to create a novel micro-interactive dual-functioning sustained-release delivery system (MIDFDS) for the treatment of glaucoma. Betaxolol hydrochloride molecule was loaded onto the montmorillonite by ion exchange and MIDFDS formation was confirmed by XPS data. MIDFDS showed similar physicochemical properties to those of Betoptic, such as particle size, pH, osmotic pressure, and rheological properties. Nevertheless, the microdialysis and intraocular pressure test revealed better in vivo performance of MIDFDS, such as pharmacokinetics and pharmacodynamics. With regards to wettability, MIDFDS had a larger contact angle (54.66 ± 5.35°) than Betoptic (36.68 ± 1.77°), enabling the MIDFDS (2.93 s) to spread slower on the cornea than Betoptic (2.50 s). Moderate spreading behavior and oppositely charged electrostatic micro-interactions had a comprehensive influence on micro-interactions with the tear film residue, resulting in a longer precorneal retention time. Furthermore, MIDFDS had a significant sustained-release effect, with complete release near the cornea. The dual-functioning sustained-release carrier together with prolonged pre-corneal retention time (80 min) provided sufficiently high drug concentrations in the aqueous humor to achieve a more stable and long-term IOP reduction for 10 h. In addition, cytotoxicity and hemolysis tests showed that MIDFDS had better biocompatibility than Betoptic. The dual-functioning microspheres presented in this study provide the possibility for improved compliance due to low cytotoxicity and hemolysis, which suggests promising clinical implications.

DOX-Loaded Gelatin Composite Hydrogels with Oxidation-Triggered Drug Release Property

Hydrogels developed as stimuli-responsive drug delivery systems (DDSs) are increasingly concerned research focus in many fields such as chemistry, functional materials and biomedicine. Herein, we report the fabrication, characterization and drug release property of new gelatin composite hydrogels by using biocompatible gelatin and the doxorubicin (DOX)-loaded micelles of a redox-responsive side-chain ferrocene (Fc)-containing amphiphilic diblock copolymer PNFc-b-PNTEG (Fig. 1). The self-assembly method was firstly adopted to prepare the DOX-loaded micelles of PNFc-b-PNTEG with oxidation-sensitive release property, and the DOX-loaded gelatin composite hydrogels were then successfully fabricated by using blending and soaking methods, respectively. The formed hydrogels were characterized by many techniques including scanning electron microscope, energy-dispersive spectroscopy, differential scanning calorimetry, thermogravimetry and swelling test. The successful encapsulation of the DOX-containing micelles in the gelatin matrix was demonstrated, and the prepared composite hydrogels exhibited improved thermal stability, faster swelling speed and higher swelling ratios. The oxidation-triggered controlled in vitro release of DOX from the composite hydrogels was confirmed by using FeCl3 at different concentrations as an oxidizing agent. The composite hydrogels could act as excellent solid carriers to guarantee the sustained-release effect of DOX, and it is feasible to keep the DOX molecules with high concentration at the specific site for a long period (20 days or so). Thus, the present composite hydrogels are anticipated to be good candidates as redox-responsive DDSs.

Berberine-10-hydroxy camptothecine-loaded lipid microsphere for the synergistic treatment of liver cancer by inhibiting topoisomerase and HIF-1α

10-HCPT is a topoisomerase I inhibitor effective in the treatment of liver cancer but its use is hampered by its resistance. The expression of hypoxia-inducible factor-1α (HIF-1α) is reportedly upregulated in liver cancer tissues, which is directly linked to the resistance of 10-HCPT. While BBR can significantly decrease the level of HIF-1α according to the literature report. Thus, the aim of this study was to prepare a novel intravenous 10-HCPT-BBR-loaded lipid microsphere (LM) and evaluate their synergistic effect on liver cancer treatment. The optimal preparation mainly included 10.0% oil phase (medium-chain triglyceride:long-chain triglyceride = 1:1), emulsifier (egg lecithin E80 and pluronic F68), antioxidant (0.02% NaHSO3), and pH regulator (0.1 mol/L Hcl). Then, the behaviors of BBR-10-HCPT loaded LM in vitro and in vivo were systematically investigated. In vitro, it showed an obvious sustained-release effect in different release mediums, good physicochemical stability at accelerated and long-term storage conditions, and great anti-proliferative capability toward human liver cancer Hep-3B cells. In vivo, the prepared LM exhibited a longer half-life and higher AUC compared to BBR injection and 10-HCPT injection. More importantly, it was found that The LM was distributed more in the liver, spleen, and tumors, but less in the lungs and heart, especially in the lung. And then, it showed significant inhibition of tumor growth against nude mouse with Hep-3B tumor, and the tumor inhibition rate reached 91.55%. Thus, the data obtained in our study suggested that BBR combined with 10-HCPT can raise curative effect and reduce the toxicity of 10-HCPT.

Development of Nitazoxanide Loaded Polymeric Nanocarriers: Box Behnken Experimental Design Based Optimisation and Characterisation

The current investigation is focused on formulation, optimisation and characterisation of polymeric based nanomaterial. Nitazoxanide (NTZ) loaded polymeric nanoparticles were prepared by homogenisation technique using Eudragit RL100 as a polymer matrix and Poly vinyl alcohol (PVA) as a cross linking agent. NTZ was used as a model drug and investigated for preformulation parameters along with excipients, identification of concentration for optimization, selection of independent (X) and dependent (Y) variables and characterisation of optimised formulation. Polymeric nanoparticles were obtained after optimization using 33 factorial design by Box Behnken Design expert (BBD). The role and influence of key process variables i.e. concentration of polymer, concentration of cross linking agent and speed of rotation of homogeniser at their respective three different levels for the optimisation of formulation were also investigated. The synthesised optimised polymeric nanoparticles were further characterised by dynamic light scattering (DLS) for its particle size (137.11nm), PDI (0.180) and zeta potential (33.4 mV) while X-ray diffraction (XRD) was used to justify the amorphous and crystalline nature of drug and excipients. Transmission electron microscopy (TEM) further revealed surface geometry of these nanoparticles being spherical in shape, drug entrapment efficiency (%DEE) was found to be 81.89% and in vitro release studies showed sustained drug release effect. The antimicrobial activity against Pseudomonas aeruginosa, Streptococcus mutans and Escherichia coli was also determined.

Preparation of Microneedle Array Mold Based on MEMS Lithography Technology.

As a transdermal drug delivery technology, microneedle array (MNA) has the characteristics of painless, minimally invasive, and precise dosage. This work discusses and compares the new MNA mold prepared by our group using MEMS technology. First, we introduced the planar pattern-to-cross-section technology (PCT) method using LIGA (Photolithography, Galvanogormung, Abformung) technology to obtain a three-dimensional structure similar to an X-ray mask pattern. On this basis, combined with polydimethylsiloxane (PDMS) transfer technology and electroplating process, metal MNA can be prepared. The second method is to use silicon wet etching combined with the SU-8 process to obtain a PDMS quadrangular pyramid MNA using PDMS transfer technology. Third method is to use the tilting rotary lithography process to obtain PDMS conical MNA on SU-8 photoresist through PDMS transfer technology. All three processes utilize parallel subtractive manufacturing methods, and the error range of reproducibility and accuracy is 2–11%. LIGA technology produces hollow MNA with an aspect ratio of up to 30, which is used for blood extraction and drug injection. The height of the MNA prepared by the engraving process is about 600 μm, which can achieve a sustained release effect together with a potential systemic delivery. The height of the MNA prepared by the ultraviolet exposure process is about 150 μm, which is used to stimulate the subcutaneous tissue.

Anti-inflammatory effect of IL-1ra-loaded dextran/PLGA microspheres on Porphyromonas gingivalis lipopolysaccharide-stimulated macrophages in vitro and in vivo in a rat model of periodontitis

Periodontitis is a multifactorial chronic infectious disease leading to a host immune response involving inflammatory cytokines, especially IL-1β, which is the main reason for further developing this disease. IL-1 receptor antagonist (IL-1ra) binds IL-1 receptor, inhibiting IL-1β signaling and reducing the levels of other cytokines closely related to periodontitis, such as IL-6 and TNF-α. Therefore, the use of IL-1ra to inhibit periodontitis development in a system, ensuring its sustained release, might be an effective way to combat this disease. Hence, in this study, a novel IL-1ra-loaded dextran/PLGA microsphere was developed to allow the sustained release of IL-1ra and enhance the anti-inflammatory properties. Therefore, this study’s purposes were to develop a novel periodontal treatment for inhibition and treatment of periodontitis and evaluate the sustained-release effect and anti-inflammatory properties of IL-1ra-loaded dextran/PLGA microspheres in vitro by cell experiments and in vivo by animal experiments. The results showed that IL-1ra-loaded dextran/PLGA microspheres were non-toxic both in vitro and in vivo and could be used as a safe and effective treatment. In addition, these microspheres could significantly prolong the half-life of IL-1ra drug, exerting a useful anti-inflammatory effect in macrophages stimulated with P. gingivalis lipopolysaccharide and in rats with periodontitis. In conclusion, IL-1ra-loaded dextran/PLGA microsphere might be a useful tool to combat periodontal disease.

The stabilization and antioxidant performances of coenzyme Q10-loaded niosomes coated by PEG and chitosan

In this study, coenzyme Q10-loaded niosomes were prepared by thin film hydration method and the niosomes were further coated with PEG and chitosan (CS) at different mass ratio of PEG (or CS) to surfactant. The effects of different formulations on the physico-chemical properties of the carriers, including encapsulation efficiency (EE), drug loading capacity (LC), particle size and zeta potential were evaluated. These niosomes, including uncoated, PEG-coated and CS-coated niosomes, were subjected to stability examination, antioxidant activity analysis and sustained release studies. The results showed that PEG and CS modification effectively improved the hydroxyl radical scavenging activity of CoQ10. PEG coating could significantly increase the stability of loaded drug, including photo stability, heat stability and storage stability, and the best one was PEG/Surf 1:2. Furthermore, compared to CoQ10 solution, the PEG-coated niosomes exhibited an excellent sustained release effects, while the CS modification had the adverse effects. In conclusion, PEG-modified niosomes can be used as a new carrier for CoQ10.

Sustained Release‐Driven Formation of Ultrastable SEI between Li6PS5Cl and Lithium Anode for Sulfide‐Based Solid‐State Batteries

AbstractThe sulfide‐type solid electrolyte (SSE) is considered a promising candidate for solid‐state lithium metal batteries (SSLMBs) owing to its advantages of superior ionic conductivity. Nevertheless, the incompatibility of the sulfide and lithium metal can result in undesirable interface resistance and rapid Li dendrite growth, which seriously hinders its commercial applications. Herein, inspired by the moderation and long duration of sustained release drug carriers when combined with active pharmaceutical ingredients in the biomedical field, poly (propylene carbonate) (PPC) and lithium bis (trifluoromethanesulfonyl) imide (LiTFSI) gradually interact with a Li anode with constantly decreased Li/SSE interfacial resistance. In addition to intimate contact, the ultrastable LiF‐enriched solid electrolyte interphase (SEI) is in situ formed via a sustained release effect, which suppresses the Li dendrite effectively. As a result, the symmetric cells demonstrate stable cycling performance for 1200 h at a current density of 0.1 mA cm−2 and 300 h at 0.5 mA cm−2. Moreover, LiFePO4/ Li6PS5Cl /Li SSLMB delivers a high discharge capacity of over 132.8 mAh g−1 for 900 cycles at 1C with steady Coulombic efficiency. Therefore, this sustained release mechanism and its initially successful application in interfacial modification increase the potential for commercial applications of SSLMBs.

Sustained-Release Method for the Directed Synthesis of ZIF-Derived Ultrafine Co-N-C ORR Catalysts with Embedded Co Quantum Dots.

M-N-C catalysts with optimized local and external structures offer great potential for replacing expensive and labile Pt-based catalysts for the oxygen reduction reaction (ORR) in fuel cells. Herein, we report a novel and facile strategy of synthesizing ultrafine ZIF-derived Co-N-C catalysts by precisely controlling the crystallization rate of ZIFs. The employment of meta-soluble Co-doped basic zinc acetate (Co-BZA), which shows a sustained-release effect in solvents, allows for the control of the solubility of Co-BZA in solvents. Detailed investigations suggest that the solubility of Co-BZA in the solvent is the key for governing the grain size of the resulting Zn/Co bimetallic ZIFs. Therefore, the self-assembly process between ligands and metal ions can be regulated by tuning the composition of mixed solvents, thus enabling rational tuning of the grain size of the resulting ZIFs. One-step pyrolysis of the ultrafine Zn/Co bimetallic ZIF precursor leads to Co and N co-doped carbon with an ultrafine grain size (termed UF Co-N-C). The Co centers that are uniformly distributed in the carbon matrix possess a quantum-dot-level grain size. Furthermore, this type of carbon nanohybrid exhibits a hierarchical pore structure, as well as a high surface area. When used as an ORR catalyst, the UF Co-N-C catalyst possesses high ORR activity (with an E1/2 of 0.9 V) that can rival 20 wt % commercial Pt/C (with an E1/2 of 0.835 V) in alkaline media. Notably, this catalyst also displays strong ORR performance similar to that of Pt/C in acidic media. The superior durability and methanol tolerance in both alkaline and acidic media for UF Co-N-C compared to Pt/C illustrate its great potential in replacing commercial Pt/C catalysts. The outstanding ORR performance of UF Co-N-C could be attributed to the simultaneous optimization of both external structures and active sites, demonstrating the effectiveness of this strategy in constructing ORR catalysts with controlled structures and desired functionalities.

BMP-6 carrying metal organic framework-embedded in bioresorbable electrospun fibers for enhanced bone regeneration

Biomolecule carrier structures have attracted substantial interest owing to their potential utilizations in the field of bone tissue engineering. In this study, MOF-embedded electrospun fiber scaffold for the controlled release of BMP-6 was developed for the first time, to enrich bone regeneration efficacy. The scaffolds were achieved by first, one-pot rapid crystallization of BMP-6 encapsulated ZIF-8 nanocrystals-as a novel carrier for growth factor molecules- and then electrospinning of the blending solution composed of poly (ε-caprolactone) and BMP-6 encapsulated ZIF-8 nanocrystals. BMP-6 molecule encapsulation efficiency for ZIF-8 nanocrystals was calculated as 98%. The in-vitro studies showed that, the bioactivity of BMP-6 was preserved and the release lasted up to 30 days. The release kinetics fitted the Korsmeyer-Peppas model exhibiting a pseudo-Fickian behavior. The in-vitro osteogenesis studies revealed the superior effect of sustained release of BMP-6 towards osteogenic differentiation of MC3T3-E1 pre-osteoblasts. In-vivo studies also revealed that the sustained slow release of BMP-6 was responsible for the generation of well-mineralized, new bone formation in a rat cranial defect. Our results proved that; MOF-carriers embedded in electrospun scaffolds can be used as an effective platform for bone regeneration in bone tissue engineering applications. The proposed approach can easily be adapted for various growth factor molecules for different tissue engineering applications.

Gefitinib encapsulation based on nano-liposomes for enhancing the curative effect of lung cancer

ABSTRACT Gefitinib (GEB) is one of the drugs used for patients with epidermal growth factor receptor (EGFR)-positive mutations in non-small cell lung cancer (NSCLC). However, application of GEB is limited by its low water solubility, stability, and utilization rate, especially the side effects while GEB is given by oral. In this study, nanoliposome was used as a carrier to prepare nanoliposome compound drug (GL) by embedding GEB in the nanoliposome perfectly combined with green nontoxic solvent and thin-film dispersion method. The nanoliposome structure was expected to improve the water solubility and biocompatibility of GEB, thus improving the effect of cancer treatment. The surface electronegative nanoliposomes can effectively avoid protein adsorption and prolong the circulation time in vivo. Meanwhile, the ratio of lecithin to cholesterol (LE/CH) was explored to maximize the encapsulation efficiency of nanoliposome. Subsequent test results showed that GL exhibited better stability, smaller particle size and higher encapsulation efficiency. In addition, in vitro drug release curve also further confirmed that GL had a promising drug sustained-release effect. In particular, a series of in vitro tests such as cell activity, apoptosis, colony formation, scratch, invasion, and cell cycle assays were performed. The results indicated that GL significantly enhanced the pro-apoptotic effect on A549 cells. Most cell cycles of A549 cells were blocked in the G0/G1 phase influenced by GL, thus inhibiting the proliferation of cancer cells. In vivo anti-tumor studies showed that compared with pure GEB, GL had a significant inhibiting effect on NSCLC. In conclusion, the GL which was synthesized by a simple method in this study significantly improved the treatment effect of cancer cells, which proved that the nanoliposome carrier had an excellent application prospect in the treatment of lung cancer.

Therapeutic Effect of Calcipotriol Pickering Nanoemulsions Prepared by Exopolysaccharides Produced by Bacillus halotolerans FYS Strain on Psoriasis.

PurposeMany exopolysaccharides (EPS) have significant emulsifying activity. Some EPS produced by the marine bacterial strain FYS have stronger emulsifying activity in the form of nanoparticles, suggesting that they could potentially form Pickering emulsions. We prepared novel EPS/CT Pickering nanoemulsions (ECPN) with EPS as emulsifiers and assessed their ability to ameliorate the poor permeability of calcipotriol (CT) in skin affected by psoriasis vulgaris.MethodsA strain of marine bacterium FYS was identified. Molecular weight, monosaccharide composition and microstructure of EPS were determined by gel permeation chromatography, high-performance liquid chromatography and scanning electron microscopy. EPS nanoparticles were prepared by adjusting the pH, and the emulsifying activity was studied at different pH. ECPN were prepared by ultrasound and optimized by the response surface method. The size distribution, microstructure, stability and in vitro drug release of ECPN were studied. The therapeutic effect of ECPN on psoriasis vulgaris was explored by animal experiments and characterizing histomorphology in vivo.ResultsA phylogenetic tree revealed that FYS was a Bacillus halodurans strain. EPS produced by the strain were heteropolysaccharides with a three-dimensional network composed of glucose, galactose, glucuronic acid, rhamnose, galacturonic acid and mannose (32.0:34.3:9.7:7.4:10.3:6.3). The EPS can form nanoparticles at pH = 4–6 with enhanced emulsifying ability. Transmission electron microscopy revealed that EPS nanoparticles adhered to the surface of oil droplets to stabilize the emulsions via a Pickering emulsification mechanism. The prepared ECPN have high stability with a sustained-release effect. Finally, animal experiments showed that ECPN effectively shortened the treatment course of psoriasis vulgaris.ConclusionEPS is highly possible to have the potential Pickering emulsification mechanism. The stability of the nanoemulsion was high. ECPN also showed potential for use in the treatment of psoriasis vulgaris. This study provides new insight into the medical applications of EPS and the treatment of psoriasis.

Therapeutic Effects of Paclitaxel Loaded Polyethylene Glycol-Polylactic Acid-Glycolic Acid Copolymer Nanoparticles on Pancreatic Cancer in Rats.

To establish a simple and safe method for the preparation of paclitaxel PEG-PLGA nanoparticles emulsified in tpgs (PTX-pegpllga-np), for high drug loading; and to study its effect on proliferation and apoptosis of human pancreatic cancer cell line MIAPACA-2. PTX-PEG-PLGA-NP was prepared by one-step precipitation, using tpgs as emulsifier. The drug loading and particle size were used as an index to optimize the formulation, and the physical and chemical properties such as in vitro release and stability were characterized. The uptake of fluorescein coumarin 6 (C6) loaded PEG-PLGA-NP by MIAPACA-2 cells was observed by fluorescence microscope, and the growth and apoptosis of MIAPACA-2 cells after PTX-PEG-PLGA-NP were detected by MTT and flow cytometry respectively. The entrapment efficiency of the nanoparticles was 90.26%, the drug loading was 10.13%, the average particle size was 92.3±3.1 nm, and the zeta potential was 10.48±1.54 mV. The cumulative releases of nano preparation and general preparation (Taxol injection) in four hours were 25.9% and 98.5%, respectively; and the former had a strong sustained-release effect. The results of cell uptake experiments showed that the uptake of c6-PEG-PLGA-NP by MIAPACA-2 cells increased gradually with time. MTT results showed that PTX-PEG-PLGA-NP had no significant difference in the inhibition rate of MIAPACA-2 cells compared with PTX group. Flow cytometry showed that PTX-PEG-PLGAnp was superior better than PTX in inducing apoptosis in MIAPACA-2 cells. The tpgs emulsification method is simple and environment-friendly. The paclitaxel loaded nanoparticles prepared through the optimization of the formulation have large drug loading capacity and uniform particle size, which can target the pancreatic cancer MIAPACA-2 cells, and do not weaken its ability to inhibit the growth of MIAPACA-2 cells. The nanoparticles also induce apoptosis in cancer MIAPACA-2 cells, and could be used for further clinical treatment of pancreatic cancer.

Shear-Thinning Viscous Materials for Subconjunctival Injection of Microparticles.

While drug-loaded microparticles (MPs) can serve as drug reservoirs for sustained drug release and therapeutic effects, needle clogging by MPs poses a challenge for ocular drug delivery via injection. Two polymers commonly used in ophthalmic procedures-hyaluronic acid (HA) and methylcellulose (MC)-have been tested for their applicability for ocular injections. HA and MC were physically blended with sunitinib malate (SUN)-loaded PLGA MPs for subconjunctival (SCT) injection into rat eyes. The HA and MC viscous solutions facilitated injection through fine-gauged needles due to their shear-thinning properties as shown by rheological characterizations. The diffusion barrier presented by HA and MC reduced burst drug release and extended overall release from MPs. The significant level of MP retention in the conjunctiva tissue post-operation confirmed the minimal leakage of MPs following injection. The safety of HA and MC for ocular applications was demonstrated histologically.

Delivery of apigenin-loaded magnetic Fe2O3/Fe3O4@mSiO2 nanocomposites to A549 cells and their antitumor mechanism

This study introduces a mesoporous magnetic nano-system for the delivery of apigenin (API). A targeted therapeutic drug delivery system was prepared based on Fe2O3/Fe3O4@mSiO2-HA nanocomposites. Magnetic Fe2O3/Fe3O4 heterogeneous nanoparticles were first prepared via the rapid-combustion process. The effects of solvent type, solvent volume, calcination temperature, and calcination time on the crystal size and magnetism of the Fe2O3/Fe3O4 heterogeneous nanoparticles were investigated. The mesoporous silica shell was deposited on the Fe2O3/Fe3O4 heterogeneous nanoparticles using an improved Stöber method. HA was exploited as the targeting ligand. The specific surface area of the Fe2O3/Fe3O4@mSiO2 nanocomposites was 369.6 m2/g, which is 19 times higher than that of the magnetic Fe2O3/Fe3O4 heterogeneous nanoparticle cores. Drug release properties from the Fe2O3/Fe3O4@mSiO2-HA nanocomposites were studied, and the result showed that API-loaded nano-system had sustained release effect. Prussian blue staining and electrochemical performance variation showed that an external magnetic field facilitated cell uptake of Fe2O3/Fe3O4@mSiO2-HA nanocomposites. MTT assays showed that the cell inhibition effect of API-Fe2O3/Fe3O4@mSiO2-HA was stronger than that of free API at the same drug dose under a magnetic field and Fe2O3/Fe3O4@mSiO2-HA nanocomposites showed good biocompatibility. Fluorescence imaging, flow cytometry, western blot, reactive oxygen species (ROS), Superoxide dismutase (SOD) and malondialdehyde (MDA) kits verified that the enhanced therapeutic action was due to the promotion of apoptosis, lipid peroxidation, and ferroptosis. The magnetic nano-system (Fe2O3/Fe3O4@mSiO2-HA) showed good magnetic targeting and active hyaluronic acid targeting, and has the potential to provide a targeted delivery platform for many antitumor drugs.

A strategy to synthesize pomegranate‐inspired hollow mesoporous molecularly imprinted nanoparticles by organic‐organic self‐assembly of dopamine

AbstractMolecularly imprinted polymers (MIPs) have attracted tremendous attention as potential materials, but the conventional MIPs preparation limits its application. In this study, a novel strategy to synthesize pomegranate‐inspired hollow mesoporous molecularly imprinted nanoparticles (HMMINs) by organic‐organic self‐assembly of dopamine is reported. Benefiting from the unique chemical composition and architecture, the one‐pot synthesized HMMINs not only provide high imprinting efficiency and binding capacity, but possess biocompatibility, photothermal (PT) and sustained release effect, which indicates HMMIPDAs have great potential to be applied as a sorbent to increase the selectivity of analytes from complex matrices, and drug carrier for PT therapy to achieve sustained‐release of the drug.