UC781: BETA-CYCLODEXTRIN COMPLEXATION AND FORMULATION AS AN ANTI-HIV MICROBICIDE

ABSTRACTBackground: UC781, a tight-binding non-nucleotide reverse transcriptase inhibitor (NNRTI) of HIV-1, is a thiocarboxanilide that has been identified as a potential microbicide agent. UC781 prevents HIV-1 infection by potently inhibiting HIV-1 replication (EC50„l8nM) with a broad therapeutic index (>62,000). However, its extremely poor water solubility leads to a great challenge for its formulation development. A beta-cyclodextrin (beta-CD) based drug delivery system was developed for UC781 to overcome this issue.Method: The complex of UC781: beta-CD was assessed with UV, FTIR, DSC, and NMR. An HPLC method was used to investigate the thermodynamic behavior of the UC781 complex. Complexation of UC781 with either hydroxypropyl -beta-Cyclodextrin (HP-beta-CD) or methyl-beta-cyclodextrin (M-beta-CD) was optimized by evaluation of four processing methods (autoclave, lyophilization, shaking, and kneading), incorporation of four water-soluble polymers (HPMC, HEC, PVA, and PVP K30), and utilization of three buffering systems (pH 7.0, 9.0 and 11.0). Finally, three formulations¡Xmethylcellulose (MC) gel, hydroxyethylcellulose (HEC) gel, and polyvinyl alcohol (PVA) film¡Xwere developed for UC781. The physical properties, toxicity, and anti-HIV activity of UC781 containing formulations were evaluated with in vitro and ex vivo models. Results: Complexation of UC781 with beta-CDs was confirmed and characterized with UV, FTIR, DSC, and NMR. UC781¡¦s complexation was found to be an enthalpy driven process. The solubility of UC781 was increased from almost none to 35 ug/ml in 15% HP-beta- CD and 180 ug/ml in 15% M-beta- CD solutions after optimization.Complexation technique significantly improved the release of UC781 from all three formulations. The complexation of UC781 with HP-beta- CD or M-beta- CD greatly increased the osmolality and decreased the viscosity of MC and HEC gel; shortened the disintegration time of PVA film; and reduced IC50 for UC781 in all three formulations. No observed toxicity was found in all complexed UC781 containing formulations.Conclusion:beta-CD complexation technique provided an effective method to overcome the aqueous solubility challenge for UC781. UC781 complexation can be used as a safe and effective drug delivery system for UC781. Of the formulations tested, PVA film with complexed UC781 provided the most promising option for microbicide product development

Structural and electronic properties of ScnOm (n=1~3, m=1~2n) clusters: Theoretical study using screened hybrid density functional theory

The structural and electronic properties of small scandium oxide clusters ScnOm (n = 1 - 3, m = 1 - 2n) are systematically studied within the screened hybrid density functional theory. It is found that the ground states of these scandium oxide clusters can be obtained by the sequential oxidation of small "core" scandium clusters. The fragmentation analysis demonstrates that the ScO, Sc2O2, Sc2O3, Sc3O3, and Sc3O4 clusters are especially stable. Strong hybridizations between O-2p and Sc-3d orbitals are found to be the most significant character around the Fermi level. In comparison with standard density functional theory calculations, we find that the screened hybrid density functional theory can correct the wrong symmetries and yield more precise description for the localized 3d electronic states of scandium.Comment: 8 figure

Co-projection-plane based 3-D padding for polyhedron projection for 360-degree video

The polyhedron projection for 360-degree video is becoming more and more popular since it can lead to much less geometry distortion compared with the equirectangular projection. However, in the polyhedron projection, we can observe very obvious texture discontinuity in the area near the face boundary. Such a texture discontinuity may lead to serious quality degradation when motion compensation crosses the discontinuous face boundary. To solve this problem, in this paper, we first propose to fill the corresponding neighboring faces in the suitable positions as the extension of the current face to keep approximated texture continuity. Then a co-projection-plane based 3-D padding method is proposed to project the reference pixels in the neighboring face to the current face to guarantee exact texture continuity. Under the proposed scheme, the reference pixel is always projected to the same plane with the current pixel when performing motion compensation so that the texture discontinuity problem can be solved. The proposed scheme is implemented in the reference software of High Efficiency Video Coding. Compared with the existing method, the proposed algorithm can significantly improve the rate-distortion performance. The experimental results obviously demonstrate that the texture discontinuity in the face boundary can be well handled by the proposed algorithm.Comment: 6 pages, 9 figure

Design and Realization of Automatic Warehouse Based on S7-1500PLC

In order to improve the efficiency of automatic warehouse control system,the experimental platform of stereoscopic warehouse with s7-1500plc is designed.The manipulator is driven by stepper motor and servo motor to realize x,y and Z three-axis space motion.The material transmission system is built by general-purpose G120 inverter. HMI KTP700 realizes control and status monitoring.The materials are identified and classified by RFID sensor and other sensors.TIAV15 software build PROFINET communication and PROFIBUS communication network.Using the GRAPH language programming can improve the visualization degree of application and solve the complex problems of program design and debugging of the warehouse control system.Through the design of hardware and software,a set of complete control system design scheme is formed,which has high practical value and provides an excellent teaching and experiment platform for the intelligent storage system

Atomic resolution imaging at 2.5 GHz using near-field microwave microscopy

Atomic resolution imaging is demonstrated using a hybrid scanning tunneling/near-field microwave microscope (microwave-STM). The microwave channels of the microscope correspond to the resonant frequency and quality factor of a coaxial microwave resonator, which is built in to the STM scan head and coupled to the probe tip. We find that when the tip-sample distance is within the tunneling regime, we obtain atomic resolution images using the microwave channels of the microwave-STM. We attribute the atomic contrast in the microwave channels to GHz frequency current through the tip-sample tunnel junction. Images of the surfaces of HOPG and Au(111) are presented.Comment: 9 pages, 5 figures, submitted to Applied Physics Letter