硬段含量对嵌段聚脲结构与性能的影响

以端氨基聚醚、异佛尔酮二异氰酸酯(IPD I)、二乙基甲苯二胺(DETDA)为主要原料,制备了一组硬段含量不同的IPD I基聚脲。通过FT-IR、DSC、SEM以及拉伸等测试手段,研究了硬段含量对聚脲羰基氢键化程度、微观结构及其力学性能的影响。结果表明:随着硬段含量的增加,脲羰基氢键化程度增加;软段相的微相分离率降低,硬段有序程度增大。硬段含量为35%时材料的力学性能较佳。     

Optimisation of rosemary oil encapsulation in polycaprolactone and scale-up of the process

Abstract

Rosemary essential oil (REO) has many biological activities, such as antioxidant, anticarcinogenic, cognition-enhancing, analgesic and antimicrobial activities. The aim of this study was to prepare, at laboratory scale and larger scale, nanoencapsulating REO in order to reduce its volatilisation, light sensitivity and to enhance its water solubility. The nanoprecipitation method was applied to prepare polycaprolactone (PCL)-based nanocapsules loaded with REO at laboratory scale and then the optimal formulation obtained was scaled-up (×6) using the membrane contactor technique. The effect of several parameters, such as the evaporation method, the type of emulsifiers and the amount of the formulation products (PCL, REO, emulsifiers, etc.) on the REO-loaded nanocapsules properties (mean size, polydispersity index (PdI), zeta potential and REO loss) was evaluated at laboratory scale in order to obtain the optimal formulation. REO-loaded nanocapsules obtained from nanoprecipitation presented a nanometric mean size (220?±?10?nm) with a PdI below 0.25, indicating an adequate homogeneity of the system, a negative zeta potential (?19.9?±?4.6?mV) and a high encapsulation efficiency (～99% for the major components). In addition, the membrane contactor technique gave similar results using an adequate pressure of the organic phase (0.8–1.2?bar). It is then suggested that the nanoprecipitation method can be suitable for the preparation of essential oil-loaded nanocapsules.     

Encapsulation of In Situ Nanoprecipitated Inorganic Materials in Confined Geometries Into a Polymer Shell Using Inverse Miniemulsion

Highly insoluble inorganic nanoparticles can be prepared in situ by precipitation inside of aqueous nanodroplets of cosonicated inverse miniemulsions containing salts, which are readily soluble in water. If the different salt droplets are fused, a hardly soluble salt is formed in the dispersed phase with a size considerably smaller than the size of the droplets. Subsequent encapsulation of the nanoparticles into a polymer shell is achieved by an interfacial polyaddition reaction between a polyol present in the aqueous phase and a (second) monomer (2,4‐toluene diisocyanate (TDI)) in the continuous phase. The materials are studied by transmission electron microscopy, X‐ray diffraction, dynamic light scattering (DLS), and TGA.     

载天冬酰胺酶自组装纳米囊的药动学及生物等效性

目的 研究载天冬酰胺酶(Asp)自组装透明质酸-聚乙二醇(HA-g-PEG)/二甲基-β环糊精(DCD)纳米囊(AHDPs)在雄性SD大鼠体内的药代动力学和生物等效性.方法 考察了AHDPs的透射电镜、粒径、zeta电位、包封率,并分别测定大鼠静脉给予AHDPs和游离Asp后,不同时间点大鼠血浆样品中Asp的活性.采用DAS 2.1.1软件计算药动学参数,对AHDPs和游离Asp进行生物等效性评价.结果 AHDPs的平均粒径为(439.63±8.49) nm,zeta电位为(-20.43±2.20) mV,平均包封率为(55.75±4.11)％(n=3).AHDPs和游离Asp的主要药动学参数AUC0-48h分别为(138.93±0.89)U· mL-1·h和(46.38±1.98) U· mL-1·h,AUC0-∞分别为(175.22±13.59)U·mL-1·h和(51.44±3.01)U·mL-1·h,t1/2分别为(4.46±1.04)h和(1.86±0.38)h.与游离Asp比较,AHDPs的AUC0-48 h、AUC0-∞和t1/2分别提高至约游离ASP的3.00、3.40和2.40倍.AUC0-48 h、AUC0-∞和Cmax的90％置信区间分别为76.9％～78.3％、76.9％～78.3％、92.8％～94.4％.结论 AHDPs延长了Asp在大鼠体内的生物半衰期,提高了Asp在大鼠体内的生物利用度,且AHDPs与游离Asp不具有生物等效性.     

Polymeric versus lipid nanocapsules for miconazole nitrate enhanced topical delivery: in vitro and ex vivo evaluation

Nanocapsules can be equated to other nanovesicular systems in which a drug is entrapped in a void containing liquid core surrounded by a coat. The objective of the present study was to investigate the potential of polymeric and lipid nanocapsules (LNCs) as innovative carrier systems for miconazole nitrate (MN) topical delivery. Polymeric nanocapsules and LNCs were prepared using emulsification/nanoprecipitation technique where the effect of poly(ε-caprolactone (PCL) and lipid matrix concentrations with respect to MN were assessed. The resulted nanocapsules were examined for their average particle size, zeta potential, %EE, and in vitro drug release. Optimum formulation in both polymeric and lipidic nanocapsules was further subjected to anti-fungal activity and ex vivo permeation tests. Based on the previous results, nanoencapsulation strategy into polymeric and LNCs created formulations of MN with slow biphasic release, high %EE, and improved stability, representing a good approach for the delivery of MN. PNCs were best fitted to Higuchi’s diffusion while LNCs followed Baker and Lonsdale model in release kinetics. The encapsulated MN either in PNCs or LNCs showed higher cell viability in WISH amniotic cells in comparison with free MN. PNCs showed less ex vivo permeation. PNCs were accompanied by high stability and more amount drug deposition (32.2 ± 3.52 µg/cm²) than LNCs (12.7 ± 1.52 µg/cm²). The antifungal activity of the PNCs was high 19.07 mm compared to 11.4 mm for LNCs. In conclusion, PNCs may have an advantage over LNCs by offering dual action for both superficial and deep fungal infections.     

Synthesis of nanocapsules blended polymeric hydrogel loaded with bupivacaine drug delivery system for local anesthetics and pain management

Local anesthetics are used clinically for the control of postoperative pain management. This study aimed to develop chitosan (CS) with genipin (GP) hydrogels as the hydrophilic lipid shell loaded poly(ε-caprolactone) (PC) nanocapsules as the hydrophobic polymeric core composites (CS-GP/PC) to deliver bupivacaine (BPV) for the prolongation of anesthesia and pain relief. The swelling ratio, in vitro degradation, and rheological properties enhancement of CS-GP/PC polymeric hydrogel. The incorporation of PC nanocapsules into CS-GP hydrogels was confirmed by SEM, FTIR, and XRD analysis. Scanning electron microscopy results demonstrated that the CS-GP hydrogels and CS-GP/PC polymeric hydrogels have a porous structure, the pore dimensions being non-uniform with diameters between 25 and 300 μm. The in vitro drug release profile of CS-GP/PC polymeric hydrogel has been achieved 99.2 ± 1.12% of BPV drug release in 36 h. Cellular viability was evaluated using the CCK-8 test on 3T3 fibroblast cells revealed that the obtained CS-GP/PC polymeric hydrogel with BPV exhibited no obvious cytotoxicity. The CS-GP/PC polymeric hydrogel loaded with BPV showed significant improvement in pain response compared to the control group animals for at least 7 days. When compared with BPV solution, CS-GP hydrogel and CS-GP/PC polymeric hydrogel improved the skin permeation of BPV 3-fold and 5-fold in 24 h, respectively. In vitro and in vivo results pointed out PC nanocapsules loaded CS-GP hydrogel can act as effective drug carriers, thus prolonging and enhancing the anesthetic effect of BPV. Histopathological results demonstrated the excellent biodegradability and biocompatibility of the BPV-loaded CS-GP/PC polymeric hydrogel system on 7, 14, and 21 days without neurotoxicity.

HIGHLIGHTS

• Preparation and characterization of CS-GP/PC polymeric hydrogel system.
• BPV-loaded CS-GP/PC exhibited prolonged in vitro release in PBS solution.
• Cytotoxicity of BPV-loaded CS-GP/PC polymeric hydrogel against fibroblast (3T3) cells.
• Development of CS-GP/PC a promising skin drug-delivery system for local anesthetic BPV.

     

Blast Resistance of 240 mm Building Wall Coated with Polyurea Elastomer

Enhancing the blast resistance of building walls is a research hotspot in the field of anti-terrorism and explosion protection. In this study, numerical simulation and experimental verification were combined to analyze the failure phenomenon of brick masonry wall and sprayed polyurea-reinforced brick wall under contact explosion and determine the failure response parameters of the wall. The failure limit, mode, and mechanism of a 240 mm wall without reinforcement and strengthened with polyurea elastomer under different strength loads were investigated. Under contact explosion, the increase in the size of the blasting pit of the 240 mm wall gradually slowed down after the dose was increased to higher than 0.5 kg. Thereafter, the energy of the explosive load was released by splashing wall fragments as well as by deflecting and movement of the wall. The results show that the 240 mm walls sprayed with polyurea elastomer had outstanding anti-explosion performance because it wraps the damaged area and fragments of masonry wall inside the polyurea layer. When the thickness of the polyurea layer increases to 8 mm, the damaged area of the masonry wall decreases by 55.6% compared with that without reinforcement. The numerical simulation results were in good agreement with the experimental results.     

Visualization of Insulin-Loaded Nanocapsules: In Vitro and in Vivo Studies After Oral Administration to Rats

Purpose. Biodegradable poly(isobutylcyanoacrylate) nanocapsules have been recognized as a promising carrier for oral administration of peptides and proteins. In the present study, we investigate the fate of insulin-loaded nanocapsules by fluorescence and transmission electron microscopy (TEM) after intragastric force-feeding to rats. Methods. Insulin-, Texas-red^®-labeled insulin, or gold-labeled insulin-loaded nanocapsules were first characterized. Rats received a single dose of nanocapsules (diameter 60-300 nm, 57 IU insulin/kg) by intragastric force-feeding. After 90 min, ileum was isolated and prepared for fluorescence and transmission electron microscopy. Results. Nanocapsules were observed on both sides of the gut epithelium and in blood capillaries. In M-cell-free epithelium, apparently intact nanocapsules could be seen in the underlying tissue, suggesting they could cross the epithelium and carry the encapsulated peptide. In M-cell-containing epithelium, nanocapsules appeared degraded in the vicinity of macrophages. It is noteworthy that intestinal absorption of nanocapsules was observed without artifacts forcing the nanocapsules to stay in the gut. Conclusions. Based on TEM observations, this study shows the intestinal absorption of biodegradable nanocapsules leading to the transport of insulin across the epithelium mucosa. The fate of the nanocapsules appeared different depending on the presence or the absence of M cells in the intestinal epithelium.     

Enzyme-based intravascular defense against organophosphorus neurotoxins: Synergism of dendritic-enzyme complexes with 2-PAM and atropine

Novel, enzyme-complexed, nano-delivery systems have been developed to antagonize the lethal effects of organophosphorus (OP) molecules such as diisopropylfluorophosphate and paraoxon. Polymeric nanocapsules can be used to deliver metabolizing enzymes to the circulation, often increasing the enzyme's efficacy by extending their circulatory life and, in some cases, enhancing their specific activity. The bacterial enzymes organophosphorus hydrolase (OPH) and organophosphorus anhydrolase (OPAA) were encapsulated within a nanocapsule, polyoxazoline-based dendritic polymer carrier and employed in combination with the OP antagonists pralidoxime (2-PAM) and atropine. The effective doses for OPH and OPAA, respectively, were 500–550 and 1500–1650 units/kg mice; the size of the entire complex is approximately 200 nm in diameter. These studies compare the efficacy of the two enzymes as prophylactic systems encapsulated within the dendritic polymer. When used in combination with 2-PAM and atropine, the dendritic encapsuled OPAA provided a 25×LD₅₀ protection against DFP intoxication, while the similarly constructed OPH complex showed a more dramatic protection (780×LD₅₀) against paraoxon intoxication in Balb/c mice. The studies demonstrate a synergistic enhancement of the antagonist, since the antidotal protection of 2-PAM+atropine against DFP and paraoxon is approximately 8 and 60×LD₅₀, respectively.     

Methods for the Preparation and Manufacture of Polymeric Nanoparticles

This review summarizes the different methods of preparation of polymer nanoparticles including nanospheres and nanocapsules. The first part summarizes the basic principle of each method of nanoparticle preparation. It presents the most recent innovations and progresses obtained over the last decade and which were not included in previous reviews on the subject. Strategies for the obtaining of nanoparticles with controlled in vivo fate are described in the second part of the review. A paragraph summarizing scaling up of nanoparticle production and presenting corresponding pilot set-up is considered in the third part of the review. Treatments of nanoparticles, applied after the synthesis, are described in the next part including purification, sterilization, lyophilization and concentration. Finally, methods to obtain labelled nanoparticles for in vitro and in vivo investigations are described in the last part of this review.