Tunable rigidity of PLGA shell-lipid core nanoparticles for enhanced pulmonary siRNA delivery in 2D and 3D lung cancer cell models.

Faced with the threat of lung cancer-related deaths worldwide, small interfering RNA (siRNA) can silence tumor related messenger RNA (mRNA) to tackle the issue of drug resistance with enhanced anti-tumor effects. However, how to increase lung tumor targeting and penetration with enhanced gene silencing are the issues to be addressed. Thus, the objective of this study is to explore the feasibility of designing non-viral siRNA vectors for enhanced lung tumor therapy via inhalation. Here, shell-core based polymer-lipid hybrid nanoparticles (HNPs) were prepared via microfluidics by coating PLGA on siRNA-loaded cationic liposomes (Lipoplexes). Transmission electron microscopy and energy dispersive spectroscopy study demonstrated that HNP consists of a PLGA shell and a lipid core. Atomic force microscopy study indicated that the rigidity of HNPs could be well tuned by changing thickness of the PLGA shell. The designed HNPs were muco-inert with increased stability in mucus and BALF, good safety, enhanced mucus penetration and cellular uptake. Crucially, HNP1 with the thinnest PLGA shell exhibited superior transfection efficiency (84.83%) in A549 cells, which was comparable to that of lipoplexes and Lipofectamine 2000, and its tumor permeability was 1.88 times that of lipoplexes in A549-3T3 tumor spheroids. After internalization of the HNPs, not only endosomal escape but also lysosomal exocytosis was observed. The transfection efficiency of HNP1 (39.33%) was 2.26 times that of lipoplexes in A549-3T3 tumor spheroids. Moreover, HNPs exhibited excellent stability during nebulization via soft mist inhaler. In conclusion, our study reveals the great potential of HNP1 in siRNA delivery for lung cancer therapy via inhalation.

Exploring the potential to enhance drug distribution in the brain subregion via intranasal delivery of nanoemulsion in combination with borneol as a guider.

The number of people with Alzheimer's disease (AD) is increasing annually, with the nidus mainly concentrated in the cortex and hippocampus. Despite of numerous efforts, effective treatment of AD is still facing great challenges due to the blood brain barrier (BBB) and limited drug distribution in the AD nidus sites. Thus, in this study, using vinpocetine (VIN) as a model drug, the objective is to explore the feasibility of tackling the above bottleneck via intranasal drug delivery in combination with a brain guider, borneol (BOR), using nanoemulsion (NE) as the carrier. First of all, the NE were prepared and characterized. In vivo behavior of the NE after intranasal administration was investigated. Influence of BOR dose, BOR administration route on drug brain targeting behavior was evaluated, and the influence of BOR addition on drug brain subregion distribution was probed. It was demonstrated that all the NE had comparable size and similar retention behavior after intranasal delivery. Compared to intravenous injection, improved brain targeting effect was observed by intranasal route, and drug targeting index (DTI) of the VIN-NE group was 154.1%, with the nose-to-brain direct transport percentage (DTP) 35.1%. Especially, remarkably enhanced brain distribution was achieved after BOR addition in the NE, with the extent depending on BOR dose. VIN brain concentration was the highest in the VIN-1-BOR-NE group at BOR dose of 1 mg/kg, with the DTI reaching 596.1% and the DTP increased to 83.1%. BOR could exert better nose to brain delivery when administrated together with the drug via intranasal route. Notably, BOR can remarkably enhance drug distribution in both hippocampus and cortex, the nidus areas of AD. In conclusion, in combination with intranasal delivery and the intrinsic brain guiding effect of BOR, drug distribution not only in the brain but also in the cortex and hippocampus can be enhanced significantly, providing the perquisite for improved therapeutic efficacy of AD.

Comparison of virus-capsid mimicking biologic-shell based versus polymeric-shell nanoparticles for enhanced oral insulin delivery.

Virus-capsid mimicking mucus-permeable nanoparticles are promising oral insulin carriers which surmount intestinal mucus barrier. However, the impact of different virus-capsid mimicking structure remains unexplored. In this study, utilizing biotin grafted chitosan as the main skeleton, virus-mimicking nanoparticles endowed with biologic-shell (streptavidin coverage) and polymeric-shell (hyaluronic acid/alginate coating) were designed with insulin as a model drug by self-assembly processes. It was demonstrated that biologic-shell mimicking nanoparticles exhibited a higher intestinal trans-mucus (>80%, 10 min) and transmucosal penetration efficiency (1.6-2.2-fold improvement) than polymeric-shell counterparts. Uptake mechanism studies revealed caveolae-mediated endocytosis was responsible for the absorption of biologic-shell mimicking nanoparticles whereas polymeric-shell mimicking nanoparticles were characterized by clathrin-mediated pathway with anticipated lysosomal insulin digestion. Further, in vivo hypoglycemic study indicated that the improved effect of regulating blood sugar levels was virus-capsid structure dependent out of which biologic-shell mimicking nanoparticles presented the best performance (5.1%). Although the findings of this study are encouraging, much more work is required to meet the standards of clinical translation. Taken together, we highlight the external structural dependence of virus-capsid mimicking nanoparticles on the muco-penetrating and uptake mechanism of enterocytes that in turn affecting their in vivo absorption, which should be pondered when engineering virus-mimicking nanoparticles for oral insulin delivery.

Bimetallic oxide Cu2O@MnO2 with exposed phase interfaces for dual-effect purification of indoor formaldehyde and pathogenic bacteria.

The combination of materials with different functions is an optimal strategy for synchronously removing various indoor pollutants. For multiphase composites, exposing all components and their phase interfaces fully to the reaction atmosphere is a critical problem that needs to be solved urgently. Here, a bimetallic oxide Cu2O@MnO2 with exposed phase interfaces was prepared by a surfactant-assisted two-step electrochemical method, which shows a composite structure of non-continuously dispersed Cu2O particles anchored on flower-like MnO2. Compared with the pure catalyst MnO2 and bacteriostatic agent Cu2O, Cu2O@MnO2 respectively shows superior dynamic formaldehyde (HCHO) removal efficiency (97.2% with a weight hourly space velocity of 120 000 mL g-1 h-1) and pathogen inactivation ability (the minimum inhibitory concentration for 104 CFU mL-1 Staphylococcus aureus is 10 µg mL-1). According to material characterization and theoretical calculation, its excellent catalytic-oxidative activity is attributable to the electron-rich region at the phase interface which is fully exposed to the reaction atmosphere, inducing the capture and activation of O2 on the material surface, and then promoting the generation of reactive oxygen species that can be used for the oxidative-removal of HCHO and bacteria. Additionally, as a photocatalytic semiconductor, Cu2O further enhances the catalytic ability of Cu2O@MnO2 under the assistance of visible light. This work will provide efficient theoretical guidance and a practical basis for the ingenious construction of multiphase coexisting composites in the field of multi-functional indoor pollutant purification strategies.

Challenges and Strategies to Enhance the Systemic Absorption of Inhaled Peptides and Proteins.

Proteins and peptides-based therapeutics are making substantial access to the market due to their obvious advantages of strong potency, high specificity and desirable safety profile. However, most clinical products are mainly delivered via parenteral route with inferior convenience. Lung is an attractive non-invasive alternative passage for systemic administration of biologics with numerous outstanding features, as examples of large absorptive surface area, extensive vascularization and mild local microenvironment. Even so, mucociliary clearance, alveolar macrophage phagocytosis, enzymatic metabolism, pulmonary surfactant adsorption and limited epithelium permeability constitute major obstacles affecting the systemic absorption of inhaled proteins and peptides. This article begins by giving a brief overview of challenges for the systemic absorption of inhaled proteins and peptides, and then goes on to a comprehensive review of possible strategies for enhanced pulmonary absorption, including chemical modification, addition of protease inhibitors, incorporation of absorption enhancers, modification with fusion proteins and development of particulate-based drug delivery systems. These strategies can provide enhanced transmembrane absorption capacity while avoiding pulmonary clearance, offering a valuable reference for designing pulmonary delivery systems of protein and peptide drugs.

Hierarchical Shish-Kebab Structures Functionalizing Nanofibers for Controlled Drug Release and Improved Antithrombogenicity.

The functionalization of the fibrous scaffolds including drug loading and release is of significance in tissue engineering and regenerative medicine. Our previous results have shown that the shish-kebab structure-modified fibrous scaffold shows a completely different microenvironment that mimics the topography of the collagen fibers, which interestingly facilitates the cell adhesion and migration. However, the functionalization of the unique structure needs to be further investigated. In this study, we modified the heparin-loaded fiber with a shish-kebab structure and tuned the kebab structure as the barrier for the sustained release of heparin. The introduction of the kebab structure increases the diffusion energy barrier by extending the diffusion distance. Moreover, the discontinued surface topography of the shish-kebab structure altered the surface chemistry from hydrophobic for the original poly(ε-caprolactone) (PCL) nanofibers to hydrophilic for the PCL nanofibers with the shish-kebab structure, which might have inhibited the activation of fibrinogen and thus improved the anticoagulant ability. This synergistic effect of heparin and the kebab structure significantly promotes the endothelial cell affinity and antithrombogenicity. This method might be a viable and versatile drug delivery strategy in vascular tissue engineering.

Exploring the potential of redispersible nanocomplex-in-microparticles for enhanced oral insulin delivery.

Polyelectrolyte nanocomplex (PEC) is a promising carrier for insulin encapsulation. However, tenacious enzymatic degradation and insufficient penetration in mucus and enterocyte are the dominating obstacles for their oral insulin delivery. Besides, the rate of insulin release should be tuned to achieve desired therapeutic effect and meanwhile with scale-up potential. Thus, PEC embedded microparticles were fabricated in this study to solve the above dilemma. First of all, insulin loaded PEC with sodium dodecyl sulfate (SDS) coating was prepared by self-assembly method and then spray-dried using different ratio chitosan (CS)/ polyvinyl alcohol (PVA) as the matrix to obtain the microparticles. Influence of the CS/PVA ratio on the in vitro and in vivo properties of the redispersed PEC was investigated systemically. It was demonstrated that when CS 50 kDa was used in the matrix, all the PEC could be well redispersed with particle size less than 250 nm, and good stability in the gastrointestinal tract, further improved enzymatic stability was achieved by nanoparticles-in-microparticles design, with CS/PVA 1:1 and 4:1 groups showing better and comparable protection. Insulin release from the microparticles decreased with the increase of CS ratio in the CS/PVA matrix. Spray-dried microparticles had less influence on the mucus penetration of the in situ redispersed PEC, with enhanced insulin permeation observed in different intestinal segments in a CS/PVA ratio dependent manner. And the CS/PVA 1:1 group, which presented good enzymatic stability, enhanced mucus penetration and moderate insulin release rate, exhibited the highest relative pharmacological availability of 6.80%. In conclusion, PEC in microparticles design using CS/PVA as the composite matrix is a potential platform for enhanced oral insulin delivery.

Nanofibrous tissue engineering scaffold with nonlinear elasticity created by controlled curvature and porosity.

Micro-crimped fibers have been widely used in the field of tissue repair to mimic the natural tissue structure and mechanical properties. However, the electrospun nanofibrous membrane is a kind of dense structure, which cannot meet the requirements of mechanical properties and permeability. In this study, we prepared nanofibrous scaffold with controllable porosity and crimpness by sacrificing fiber components and releasing residual stress. The results show that the crimpness of the fiber is positively related to the porosity, and with the increase of porosity, the fiber crimpness increases greatly. Meanwhile, the scaffold modulus was reduced by 86% and the elongation at break doubled, which is similar to natural blood vessels. Moreover, it is found that the porous micro-crimped fiber scaffold promotes the adhesion and diffusion of endothelial cells, and facilitates the rapid endothelialization of the scaffold, which has a great potential for practical application.

Exploring Intestinal Surface Receptors in Oral Nanoinsulin Delivery.

Subcutaneous and inhaled insulins are associated with needle phobia, lipohypertrophy, lipodystrophy, and cough in diabetes treatment. Oral nanoinsulin has been developed, reaping the physiologic benefits of peroral administration. This review profiles intestinal receptors exploitable in targeted delivery of oral nanoinsulin. Intestinal receptor targeting improves oral insulin bioavailability and sustains blood glucose-lowering response. Nonetheless, these studies are conducted in small animal models with no optimization of insulin dose, targeting ligand type and content, and physicochemical and molecular biologic characteristics of nanoparticles against the in vivo/clinical diabetes responses as a function of the intestinal receptor population characteristics with diabetes progression. The interactive effects between nanoinsulin and antidiabetic drugs on intestinal receptors, including their up-/downregulation, are uncertain. Sweet taste receptors upregulate SGLT-1, and both have an undefined role as new intestinal targets of nanoinsulin. Receptor targeting of oral nanoinsulin represents a viable approach that is relatively green, requiring an in-depth development of the relationship between receptors and their pathophysiological profiles with physicochemical attributes of the oral nanoinsulin. SIGNIFICANCE STATEMENT: Intestinal receptor targeting of oral nanoinsulin improves its bioavailability with sustained blood glucose-lowering response. Exploring new intestinal receptor and tailoring the design of oral nanoinsulin to the pathophysiological state of diabetic patients is imperative to raise the insulin performance to a comparable level as the injection products.

Mucoadhesive versus mucopenetrating nanoparticles for oral delivery of insulin.

Mucoadhesive and mucopenetrating nanoparticles are commonly designed to improve mucosal drug delivery efficiency. Herein, in order to better understand the contribution of mucoadhesion and mucopenetration in oral delivery of biomacromolecules, insulin-loaded poly (n-butylcyanoacrylate) nanoparticles (Ins/PBCA NPs) with different coating layers, chitosan (CS) or alginate (Alg), were designed and their different absorption enhancing mechanisms were explored. It was demonstrated that both the mucoadhesive (Ins/PBCA/CS) and the mucopenetrating (Ins/PBCA/CS/Alg) nanoparticles showed good stability and similar release profiles in the gastrointestinal fluid, the mucoadhesive nanoparticles presented an enrichment in mucus (70%, 10 min) while most of the mucopenetrating nanoparticles penetrated through the mucus (80%, 10 min). Uptake mechanism studies revealed clathrin- and caveolae-mediated endocytosis were mainly involved in the intestinal transport of mucoadhesive nanoparticles while caveolae-mediated endocytosis and macropinocytosis contributed to the absorption of mucopenetrating nanoparticles, and especially, M cells favored the absorption of mucoadhesive nanoparticles. In vivo studies revealed that the mucopenetrating nanoparticles had a fast onset of action while the mucoadhesive nanoparticles presented a sustained hypoglycemic effect in diabetic rats, and overall no significant difference in pharmacological availability was found between the mucopenetrating (8.80%) and mucoadhesive nanoparticles (8.44%). To sum up, due to the varied absorption mechanism in intestine, the mucoadhesive nanoparticles designed herein had a comparable effect in enhancing oral insulin absorption compared with the mucopenetrating nanoparticles. STATEMENT OF SIGNIFICANCE: In order to improve oral delivery efficiency of insulin, insulin-loaded nanoparticles with opposite properties namely mucoadhesion and mucopenetration have been widely developed to either prolong their residence at the absorption site or improve their penetration across mucus. However, their individual contribution in oral insulin absorption is still unclear. In this paper, insulin-loaded poly (n-butylcyanoacrylate) nanoparticles with both properties were designed via different surface coating and their absorption enhancing mechanisms were explored. It was demonstrated that the mucoadhesive and mucopenetrating nanoparticles showed varied retention and mucus-penetration ability in mucus, with different absorption mechanism in intestine, but no statistical difference in pharmacological availability was found between them. Overall, the present work provides us a guidance for the design of oral nano-delivery system.

Influence of drug-carrier compatibility and preparation method on the properties of paclitaxel-loaded lipid liquid crystalline nanoparticles.

The main objective of this paper is to elucidate the influence of drug-carrier compatibility and preparation method on the properties of Paclitaxel (PTX)-loaded lipid liquid crystalline nanoparticles (LLCNs). Here, glyceryl monooleate (GMO), glycerol monolinoleate (GML), glyceryl monolinolenate (GMLO) were selected as the lipids, and Soluplus, Poloxamer 407 (P407), Tween 80 were selected as the stabilizer to prepare LLCNs. First of all, PTX-carrier compatibility was screened by molecular dynamic simulation using Flory-Huggins interaction parameter as the criteria. Thereafter, PTX-loaded LLCNs were prepared under different energy input conditions and were characterized. Influence of lipid type, stabilizer type, drug-lipid ratio and preparation method on properties of the LLCNs was explored. It was found that both lipid and stabilizer type had significant influence on drug encapsulation efficiency. Compared to the LLCNs prepared under high energy condition, PTX-loaded LLCN prepared under low energy input had higher drug encapsulation efficiency, smaller particle size (211.6 nm versus 346.8 nm) and a sustained release behavior. In conclusion, molecular dynamic simulation is an effective tool to select the most appropriate composition of LLCNs for a specific drug substance, and LLCNs prepared using low energy input methods was particularly applicable for industrial manufacture.

Design of biotin decorated enterocyte targeting muco-inert nanocomplexes for enhanced oral insulin delivery.

The natural mucus cover has been a major obstacle to prevent enterocyte targeting particles from contact with the receptors. Thus, mucus penetration and intestinal targeting should be designed into one system. Based on the concept that biotin specifically recognizes epithelium receptors, enterocyte targeting muco-inert nanocomplexes were designed. Firstly, biotinylated chitosan (CS-Biotin) copolymers with different degree of substitution were synthesized and characterized. The nanocomplexes between CS-Biotin and insulin were prepared via self-assembly method. Thereafter, the nanocomplexes were fabricated by coating with various molecular weight hyaluronic acid (HA), which improved penetration efficiency in the mucus layer and small intestine in a HA molecular weight dependent manner. In vivo study indicated that hypoglycemic effect of the nanocomplexes was biotin modification degree and HA molecular weight dependent, with HA (200)-coated CS-Biotin21.8%/Insulin polyelectrolyte complex presenting the best performance. In conclusion, biotin decorated muco-inert nanocomplexes with HA coating are a promising platform for oral insulin delivery.

Design of folic acid decorated virus-mimicking nanoparticles for enhanced oral insulin delivery.

Mucus penetration and intestinal cells targeting are two main strategies to improve insulin oral delivery efficiency. However, few studies are available regarding the effectiveness of combining these two strategies into one nano-delivery system. For this objective, the folic acid (FA) decorated virus-mimicking nanoparticles were designed and influence of FA graft ratio on the in vitro and in vivo properties of insulin loaded nanoparticles was studied systemically. Firstly, using folic acid as active ligand, different folic acid grafted chitosan copolymers (FA-CS) were synthesized and characterized. Thereafter, using insulin-loaded poly(n-butylcyanoacrylate) nanoparticles as the core, virus-mimicking nanoparticles were fabricated by coating of positively charged FA-CS copolymer and negatively charged hyaluronic acid. Irrespective of the FA graft ratio, all the nanoparticles showed good stability, similar insulin release in the gastrointestinal fluid, excellent and similar penetration in mucus. The nanoparticles permeability in intestine was FA graft ratio and segment dependent, with FA graft ratio at/over 12.51% presenting better effect in the order of duodenum > jejunum ≈ ileum. Both mechanism studies and confocal microscopy observation demonstrated FA-mediated process was involved in the transport of FA decorated nanoparticles. In vivo studies revealed hypoglycemic effect of the nanoparticles was FA graft ratio dependent, a saturation phenomenon was observed when FA graft ratio was at/over 12.51%. In conclusion, folic acid decorated virus-mimicking nanoparticles presented improved insulin absorption, implying combining mucus penetration and active transcellular transport is an effective way to promote oral insulin absorption, while the modification ratio of active ligand needs optimization.

Exploring the potential influence of drug charge on downstream deposition behaviour of DPI powders.

Dry powder inhaler (DPI) development is limited by the time- and labor-consuming in vitro lung deposition test. It's highly desirable to find an easy tool for DPI formulation screening. Dynamic powder rheological properties seem to present many advantages, however, the adoptability needs to be verified. Drug charge is an important parameter especially for DPI formulation design but how it affects the process of pulmonary drug delivery is unavailable. Therefore, the objective of this study is to explore the influence of drug charge on DPI powders, further testing the potentials of powder properties for downstream deposition behavior prediction. Taking five differently charged drugs as model, influence of drug charge on uniformity, rheological and aerodynamic properties of the mixtures were investigated systemically. It was found that mometasone furoate with near neutral charge presented better content homogeneity, while significantly decreased recovery was noted for charged drugs, such as positively charged drug (salbutamol sulphate and indacaterol maleate) mixtures and negatively charged drug (budesonide and fluticasone propionate) mixtures. Moreover, drug charge also influenced flowability and cohesion of their admixture with lactose. As for the downstream deposition, neutral drugs presented higher fine particle fraction (FPF), followed by positively charged drugs and negatively charged drugs. Good correlations between basic flowability energy, aeration energy, Permeability and FPF were established irrespective of different drugs. Principal component analysis results suggested flowability had a greater influence on FPF when mixtures were less cohesive. In conclusion, this study demonstrated drug charge can influence physicochemical, rheological and aerodynamic properties of the admixture, and DPIs' dynamic properties could be used as potential tools to predict downstream deposition with good accuracy.

Highly Efficient Removal of Methylene Blue Dye from an Aqueous Solution Using Cellulose Acetate Nanofibrous Membranes Modified by Polydopamine.

A new type of deacetylated cellulose acetate (DA)@polydopamine (PDA) composite nanofiber membrane was fabricated by electrospinning and surface modification. The membrane was applied as a highly efficient adsorbent for removing methylene blue (MB) from an aqueous solution. The morphology, surface chemistry, surface wettability, and effects of operating conditions on MB adsorption ability, as well as the equilibrium, kinetics, thermodynamics, and mechanism of adsorption, were systematically studied. The results demonstrated that a uniform PDA coating layer was successfully developed on the surface of DA nanofibers. The adsorption capacity of the DA@PDA nanofiber membrane reached up to 88.2 mg/g at a temperature of 25 °C and a pH of 6.5 after adsorption for 30 h, which is about 8.6 times higher than that of DA nanofibers. The experimental results showed that the adsorption behavior of DA@PDA composite nanofibers followed the Weber's intraparticle diffusion model, pseudo-second-order model, and Langmuir isothermal model. A thermodynamic analysis indicated that endothermic, spontaneous, and physisorption processes occurred. Based on the experimental results, the adsorption mechanism of DA@PDA composite nanofibers was also demonstrated.

Design of self-polymerized insulin loaded poly(n-butylcyanoacrylate) nanoparticles for tunable oral delivery.

Macromolecular drugs, characterized by low stability and large molecular weight, still faced various difficulties by oral administration. And controlling drugs' release rate to reach the physiological concentration in the blood was recognized as one of the main challenges in this field but no studies are available so far. Thus, the objective of this study was to investigate the effect of insulin release rate on its in vitro and in vivo behavior when other obstacles (drug stability, mucus penetration and retention in gastrointestinal tract) was firstly overcome. Using n-butylcyanoacrylate (BCA) as the carrier, insulin-loaded Poly (n-butylcyanoacrylate) nanoparticles (Ins/PBCA NPs) were prepared by self-polymerization and the release rate of insulin was controlled by adjusting the mass ratio of Insulin/BCA. The NPs exhibited good stability in gastric fluid with controlled release in intestine and the release rate increased with the increase of Insulin/BCA mass ratio. All the Ins/PBCA NPs with different release rate showed excellent mucus penetration (>60%, 10 min) and strong gastrointestinal retention (~70%, 12 h). Especially, all the NPs showed promising hypoglycemic effect with the extent depending on drug release rate. Ins/BCA = 2/10 NPs exhibited fast hypoglycemic effect, while Ins/BCA = 2/15 NPs showed slow and outstanding performance. In conclusion, Ins/PBCA NPs could not only overcome the oral barriers of insulin delivery but also provide desired hypoglycemic effect by controlling insulin release rate.

Biomimetic composite scaffolds based on surface modification of polydopamine on ultrasonication induced cellulose nanofibrils (CNF) adsorbing onto electrospun thermoplastic polyurethane (TPU) nanofibers.

To improve the interaction between cells and scaffolds, the appropriate surface chemical property is very important for tissue engineering scaffolds. In this study, the thermoplastic polyurethane (TPU) nanofibers was firstly fabricated by electrospinning technique, and then its surface was modified with cellulose nanofibrils (CNF) particles by ultrasonic-assisted to obtain TPU/CNF nanofibers. Subsequently, the TPU/CNF-polydopamine (PDA) composite nanofibers with core/shell structure were fabricated by PDA coating method. In comparison with TPU nanofibers, the uniformization of PDA coating layer on the surface of TPU/CNF composite nanofibers significantly increased due to the addition of CNF, which used as the active sites to guide the PDA particles accumulated along with the fiber direction. The water absorption and hydrophilicity of TPU/CNF-PDA composite nanofibers were significantly increased in comparison with those of TPU and TPU/CNF nanofibers. The mechanical properties of the TPU/CNF-PDA composite nanofibers were higher than those of the TPU and TPU/CNF nanofibers due to the formation of strong hydrogen bonds between PDA and TPU/CNF, making TPU, CNF and PDA strongly adhere to each other. The attachment and viability of mouse embryonic osteoblasts cells (MC3T3-E1) cultured on TPU/CNF-PDA composite nanofibers were obviously enhanced compared with TPU and TPU/CNF nanofibers. Those results suggested that the modified TPU/CNF-PDA composite nanofibers have excellent mechanical and biological properties, which promoting them potentially useful for tissue engineering scaffolds. The presented strategy represents a general route to modify the surface of scaffolds, which are promising for tissue engineering applications.

Elucidation of alginate-drug miscibility on its crystal growth inhibition effect in supersaturated drug delivery system.

The objective of this study is to investigate the influence of drug-alginate miscibility on maintaining drug supersaturation. Using lovastatin, indomethacin, itraconazole as model drugs, drug-alginate miscibility was estimated by Hansen solubility parameters. The mechanism of drug-alginate miscibility on maintaining drug supersaturation was elucidated by microscopy, molecular mobility (T2), FTIR and X-ray crystallography. The influence of alginate properties on maintaining drug supersaturation was also examined. It was demonstrated that the capacity of alginate to maintain drug supersaturation was dependent on alginate-drug miscibility. Further mechanistic study revealed that alginate interacts with drugs via hydrogen bonding at different extent based on varied drug-alginate miscibility. Alginate could suppress drug molecular mobility and corresponding crystal growth inhibition. The properties of alginate also play an important role in maintaining drug supersaturation. In conclusion, alginate could be used as a potential crystal growth inhibitor, and the crystal growth inhibition effect depends on drug-alginate miscibility and alginate properties.

Dual super-amphiphilic modified cellulose acetate nanofiber membranes with highly efficient oil/water separation and excellent antifouling properties.

Along with increasing oily, industrial wastewater and seawater pollution, oil spills-and their clean-up via the separation of oil and water-are still a worldwide challenge. Aiming to fabricate an oil/water separation membrane with excellent comprehensive performance, we report here a new type of multifunctional deacetylated cellulose acetate (d-CA) membrane. The cellulose acetate (CA) nanofiber membranes are fabricated by electrospinning and then deacetylated to obtain the d-CA nanofiber membranes, which are super-amphiphilic in air, oleophobic in water, and super-hydrophilic in oil. The multifunctional d-CA nanofiber membranes can be used as water-removal substances for oil/water mixtures, as well as emulsified oil/water and oil/corrosive aqueous systems, with gravity as the only needed driving force. The d-CA nanofiber membranes possess the highest separation flux, reaching up to 38,000 L/m2·h, and the highest separation efficiency, reaching up to 99.97 % for chloroform/water mixtures under the force of gravity. In fact, the separation flux was several times higher than that of commercial CA (c-CA) membranes. The excellent anti-pollution and self-cleaning abilities endow the membranes with powerful cyclic stability and reusability. The d-CA nanofiber membranes show great application prospects in chemical plants, textile mills, and the food industry, as well as offshore oil spills, to separate oil from water.

Contact Angle Measurements: an Alternative Approach Towards Understanding the Mechanism of Increased Drug Dissolution from Ethylcellulose Tablets Containing Surfactant and Exploring the Relationship Between Their Contact Angles and Dissolution Behaviors.

The addition of surfactant in tablet was a well-defined approach to improve drug dissolution rate. While the selected surfactant played a vital role in improving the wettability of tablet by medium, it was equally important to improve the dissolution rate by permeation effect due to production of pores or the reduced inter-particle adhesion. Furthermore, understanding the mechanism of dissolution rate increased was significant. In this work, contact angle measurement was taken up as an alternative approach for understanding the dissolution rate enhancement for tablet containing surfactant. Ethylcellulose, as a substrate, was used to prepare tablet. Four surfactants, sodium dodecyl sulfate (SDS), sodium dodecylbenzenesulfonate (SDBS), dodecyltrimethylammonium bromide (DTAB), and sodium lauryl sulfonate (SLS), were used. Berberine hydrochloride, metformin hydrochloride, and rutin were selected as model drugs. The contact angle of tablet in the absence and presence of surfactant was measured to explore the mechanism. The dissolution test was investigated to verify the mechanism and to establish a correlation with the contact angle. The result showed that the mechanism was the penetration effect rather than the wetting effect. The dissolution increased with a reduction in the contact angle. DTAB was found to obtain the highest level of dissolution enhancement and the lowest contact angle, while SDS, SDBS, and SLS were found to be the less effective in both dissolution enhancement and contact angle decrease. Therefore, contact angle was a good indicator for dissolution behavior besides exploring the mechanism of increased dissolution, which shows great potential in formula screening.