Aiming at the target allocation of multi-aircraft cooperative air combat, an improved artificial immune algorithm is proposed based on the modeling for comprehensive superiority function. Firstly, the random generation method and artificial construction method are used to create two initial populations, which ensure the diversity of the initial populations; following is to evolve the populations by adopting two different selection, crossover and mutation operations; then, the designed new immigration operator is used to exchange information among the populations, which further increases the diversity of the populations and improves the search efficiency. Finally, the comparison of the improved artificial immune algorithm with the traditional artificial immune algorithm had been made. Simulation results show that the improved artificial immune algorithm can effectively improve the premature convergence problem, and the search efficiency, the optimal allocation scheme is obtained, which is suitable for target allocation problem of multi-aircraft cooperative air combat and meet the actual operational requirements.

Introduction In the previous study, nanoparticles coated with trimethyl chitosan (TMC) derivatives (PPTT-NPs) could promote the oral bioavailability of panax notoginseng saponins (PNS). Herein, we chose PPTT-NPs as a model drug to study the property and mechanism of intestinal absorption in vitro and in vivo. Methods The stability of PPTT-NPs was evaluated using simulated gastric fluid and simulated intestinal fluid. The uptake and transport of PPTT-NPs were investigated in Caco-2 and Caco-2&HT29 co-culture cells. The biosafety, intestinal permeability, adhesion, and absorption mechanism of PPTT-NPs were investigated using SD rats in vivo. The live imaging and biodistribution of PPTT-NPs were observed by IVIS. Furthermore, the effects on CYP3A4 of PPTT-NPs were investigated using testosterone as the probe substrate. Results The results of the stability assay showed that PPTT-NPs had a strong tolerance to the pH and digestive enzymes in the gastrointestinal environment. In vitro cell experiments showed that the uptake of drugs exhibited a time-dependent. When the ratio of TMC-VB 12 and TMC-Cys was 1:3, the uptake capacity of PPTT-NPs was the highest. PPTT-NPs could enhance the paracellular transport of drugs by reversibly opening a tight junction. Animal experiments demonstrated that PPTT-NPs have good biological safety. PPTT-NPs had good adhesion and permeability to small intestinal mucosa. Meanwhile, PPTT-NPs needed energy and various protein to participate in the uptake of drugs. The live imaging of NPs illustrated that PPTT-NPs could prolong the residence time in the intestine. Moreover, TMC-VB 12 and TMC-Cys could reduce the metabolism of drugs by inhibiting CYP3A4 to a certain extent. Conclusion The results show that TMC-VB 12 and TMC-Cys are effective in the transport of PPTT-NPs. PPTT-NPs can increase the intestinal adhesion of drugs and exert high permeation by intestinal enterocytes which demonstrate significant and efficient potential for oral delivery of the BCS III drugs.

Traditional Chinese medicine (TCM) oral preparations is the main means of disease treatment in TCM clinically, but the bioavailability of TCM active ingredients such as panax noteginseng saponins (PNS) is low due to its poor intestinal absorption. In this study, PNS nanoparticle modified with thiolated trimethyl chitosan (TMC-Cys) and wheat germ agglutinin (WGA) (PP-WT NPs) was prepared to promote the oral absorption of PNS effectively. In vitro studies demonstrated that PP-WT NPs delayed the release of PNS and had strong anti-enzyme activities against acids and digestive enzymes in the gastrointestinal environment. And it has good cell uptake and transport capacity in the Caco-2/HT29 co-cultured cell model. In vivo animal experiments showed that PP-WT NPs could penetrate the mucus layer barrier, and the effective permeability coefficients for R1, Rg1, and Rb1 in the small intestine were 1.68, 1.64, and 1.63 times than that of free PNS, respectively. It was predicted that panax notoginseng saponins-loaded nanoparticles modified with thiolated trimethyl chitosan and wheat germ agglutinin provide an attractive strategy for improving the oral absorption of PNS.

Introduction: With the rapid development of nanotechnology, the research and development of nano-drugs have become one of the development directions of drug innovation. The encapsulation of the nanoparticles can change the biological distribution of the drug in vivo and improve the bioavailability of the drug in vivo. Naringenin is poorly soluble in water and has a low bioavailability, thus limiting its clinical application. The main purpose of this study was to develop a nano-sized preparation that could improve the oral bioavailability of naringenin. Methods: Chitosan oligosaccharide modified naringenin-loaded bovine serum albumin nanoparticles (BSA-COS@Nar NPs) were prepared by emulsification solvent evaporation and electrostatic interaction. The nanoparticles were characterized by HPLC, laser particle size analyzer, transmission electron microscope and X-ray diffraction analysis. The release in vitro was investigated, and the behavior of nanoparticles in rats was also studied. The caco-2 cell model was established in vitro to investigate the cytotoxicity and cellular uptake of nanoparticles. Results: BSA-COS@Nar NPs were successfully prepared, and the first-order release model was confirmed in vitro release. In vivo pharmacokinetic results indicated that the area under the drug concentration-time curve (AUC) of BSA-COS@Nar NPs was 2.37 times more than free naringenin. Cytotoxicity and cellular uptake results showed that BSA-COS@Nar NPs had no significant cytotoxic effect on Caco-2 cells and promoted cellular uptake of the drug. Conclusion: BSA-COS@Nar NPs could improve the in vivo bioavailability of naringenin.