Mutual Effects of Hydrogen Bonding and Polymer Hydrophobicity on Ibuprofen Crystal Inhibition in Solid Dispersions with Poly(N-vinyl pyrrolidone) and Poly(2-oxazolines)

Poly(N-vinyl pyrrolidone) (PVP), poly(2-methyl-2-oxazoline) (PMOZ), poly(2-ethyl-2-oxazoline) (PEOZ), poly(2-n-propyl-2-oxazoline) (PnPOZ), and poly(2-isopropyl-2-oxazoline) (PiPOZ) were used to prepare solid dispersions with ibuprofen (IB), a model poorly-water soluble drug. Dispersions, prepared by solvent evaporation, were investigated using powder X-ray diffractometry, differential scanning calorimetry, and FTIR spectroscopy; hydrogen bonds formed between IB and all polymers in solid dispersions. PMOZ, the most hydrophilic polymer, showed the poorest ability to reduce or inhibit the crystallinity of IB. In contrast, the more hydrophobic polymers PVP, PEOZ, PnPOZ, and PiPOZ provided greater but similar abilities to reduce IB crystallinity, despite the differing polymer hydrophobicity and that PiPOZ is semi-crystalline. These results indicate that crystallinity disruption is predominantly due to hydrogen bonding between the drug molecules and the polymer. However, carrier properties affected drug dissolution, where PnPOZ exhibited lower critical solution temperature that inhibited the release of IB, whereas drug release from other systems was consistent with the degree of ibuprofen crystallinity within the dispersions

Synthesis and evaluation of methacrylated poly(2-ethyl-2-oxazoline) as a mucoadhesive polymer for nasal drug delivery

Methacrylated poly(2-ethyl-2-oxazoline) (PEOZ) was synthesized by partial hydrolysis of 500 kDa PEOZ, and the resulting poly[(2-ethyl-2-oxazoline)-co-ethylenimine] P(EOZ-co-EI) was subsequently reacted with methacrylic anhydride. The successful synthesis of methacrylated PEOZ (MAPEOZ) was confirmed by proton nuclear magnetic resonance (1H NMR), infrared spectroscopy, and differential scanning calorimetry. The degrees of hydrolysis and methacrylation were determined by 1H NMR spectra. MAPEOZ exhibited temperature-responsive properties, which were dependent on the degree of methacrylation. On that basis, three soluble MAPEOZ derivatives with different degrees of methacrylation were selected and investigated in cell toxicity studies, showing no significant cytotoxicity against the HEK293 cell line. A slug mucosal irritation assay showed that PEOZ and MAPEOZ do not cause mucosal irritation. The presence of methacryloyl groups and residual amines had a remarkable synergistic effect on the mucoadhesive properties of these polymers. These poly(2-ethyl-2-oxazoline) derivatives have excellent potential as mucoadhesive materials for developing formulations for drug delivery via mucosal routes of administration

Clinical Characteristics of 26 Human Cases of Highly Pathogenic Avian Influenza A (H5N1) Virus Infection in China

BACKGROUND: While human cases of highly pathogenic avian influenza A (H5N1) virus infection continue to increase globally, available clinical data on H5N1 cases are limited. We conducted a retrospective study of 26 confirmed human H5N1 cases identified through surveillance in China from October 2005 through April 2008. METHODOLOGY/PRINCIPAL FINDINGS: Data were collected from hospital medical records of H5N1 cases and analyzed. The median age was 29 years (range 6-62) and 58% were female. Many H5N1 cases reported fever (92%) and cough (58%) at illness onset, and had lower respiratory findings of tachypnea and dyspnea at admission. All cases progressed rapidly to bilateral pneumonia. Clinical complications included acute respiratory distress syndrome (ARDS, 81%), cardiac failure (50%), elevated aminotransaminases (43%), and renal dysfunction (17%). Fatal cases had a lower median nadir platelet count (64.5 x 10(9) cells/L vs 93.0 x 10(9) cells/L, p = 0.02), higher median peak lactic dehydrogenase (LDH) level (1982.5 U/L vs 1230.0 U/L, p = 0.001), higher percentage of ARDS (94% [n = 16] vs 56% [n = 5], p = 0.034) and more frequent cardiac failure (71% [n = 12] vs 11% [n = 1], p = 0.011) than nonfatal cases. A higher proportion of patients who received antiviral drugs survived compared to untreated (67% [8/12] vs 7% [1/14], p = 0.003). CONCLUSIONS/SIGNIFICANCE: The clinical course of Chinese H5N1 cases is characterized by fever and cough initially, with rapid progression to lower respiratory disease. Decreased platelet count, elevated LDH level, ARDS and cardiac failure were associated with fatal outcomes. Clinical management of H5N1 cases should be standardized in China to include early antiviral treatment for suspected H5N1 cases

Solid drug dispersions and mucoadhesive formulations with poly(2-oxazolines), poly(N-(2-hydroxylpopyl)methacrylamide) and their derivatives

The first chapter provides an overview on intermolecular interactions in solid dispersions of amide-containing nonionic water-soluble polymers including polyvinyl pyrrolidone (PVP), polyvinylpyrrolidone-co-vinyl acetate (PVP/VA), poly(N-vinyl caprolactam)–polyvinyl acetate–polyethylene glycol graft copolymer (Soluplus) and poly(2-oxazolines). Chapters 2 and 3 focus on the effects of structure and properties of PVP and poly(2-oxazolines) on solid dispersions. A series of poly(2-oxazolines) with equivalent degrees of polymerization were synthesized and these polymers and PVP were used to prepare solid dispersions with haloperidol or ibuprofen. Chapter 2 demonstrated that increasing the number of hydrophobic groups (-CH2- and -CH3) in the polymer resulted in greater inhibition of crystallinity of haloperidol. Interestingly, drug crystallization inhibition by poly(2- isopropyl-2-oxazoline) was lower than with its isomeric poly(2-propyl-2-oxazoline) because of the semi-crystalline nature of the former polymer. In order to explore the impacts of both polymer hydrophobicity and drug–polymer hydrogen bonding, in chapter 3, ibuprofen, a hydrophobic crystalline drug and strong hydrogen bond donor (because of its carboxylic group), was selected to prepare solid dispersions with poly(2-oxazolines) and PVP. Chapter 3 indicates the crystallinity disruption is predominantly due to hydrogen bonding between the drug molecule (ibuprofen) and the polymer. Both chapters show the crystallization inhibition was consistent with drug dissolution studies using these solid dispersions, with the exception of poly(2- propyl-2-oxazoline), which exhibited lower critical solution temperature that affected the release of haloperidol and ibuprofen. Chapter 4 and 5 investigate the mucoadhesion properties of modified poly(2-ethyl2-oxazoline) and poly(N-(2-hydroxylpropyl)methacrylamide) (PHPMA), respectively. In chapter 4, the presence of methacryloyl groups and residual amines in methacrylated poly(2-ethyl-2-oxazoline) had a strong synergistic effect on the mucoadhesive properties of these polymers. In chapter 5, the presence of maleimide groups was shown to positively affect the mucoadhesive properties of PHPMA. These poly(2-ethyl-2-oxazoline) derivatives and PHPMA derivatives have significant potential as mucoadhesive materials for formulation of dosage forms for nasal drug delivery. The final chapter discusses the general conclusions and possible future work. The poly(2-oxazolines) and functionalized derivatives appear to offer great potential in pharmaceutical application

Dynamic resource allocation for target tracking in sensor and robot networks

Sensor network is generally composed of a set of sensors with limited computation capability and power supply. Thus, a well-defined allocation scheme is essential for maintaining the whole sensor network. This paper investigates the dynamic resource allocation problem in a sensor and robot networks for mobile target tracking tasks. Most of sensors will be in sleep mode except for the ones that can contribute for tracking. The sensor network resource allocation is achieved by a hierarchical structure-clustering. Upon detecting an interested event, a set of sensors form a cluster. Only cluster members will be activated during the tracking task. The cluster headship and membership will be updated based on the target\u27s movement properties. In this paper, the clustering algorithm considers sensing area with communication holes and a routing tree is set up within the cluster. For a cluster with communication and/or sensing holes, mobile sensors will be deployed to enhance the sensing and communication capability in the clustering area. Simulations have been used to verify the proposed algorithm

Spatiotemporal sensor network and mobile robot coordination in constrained environments

This paper presents a multi-robot coordination architecture for a robot-sensor network to track and intercept targets. For a target tracking and interception task, the sensor network continuously tracks the targets and dynamically selects robots to intercept the target. The robots are navigated through the sensor network. The main contribution of this paper lies on providing a scalable, power saving robot selection algorithm for the sensor networks. The robot selection algorithm is addressed based on partitioning among sensor nodes. Through partitioning, the sensor nodes are grouped so that they know which robot to choose if it is the closest to the target. The partitioning is updated with respect to the movement of robots. The proposed algorithms are proven to be effective and verified by simulations. © 2006 IEEE

Multi-robot coordination for elusive target interception aided by sensor networks

This paper presente a multi-robot coordination architecture for a robot-sensor network to track and intercept targets. For a target tracking and interception task, the sensor network continuously tracks the targets and dynamically selects robots to intercept the target. The robots are navigated through the sensor network. The main contribution of this paper lies on providing a scalable, power saving robot selection algorithm for the sensor networks. The robot selection algorithm is addressed based on partitioning among sensor nodes. Through partitioning, the sensor nodes are grouped so that they know which robot to choose if it is the closest to the target. The partitioning is updated with respect to the movement of robots. The proposed algorithms are proven to be effective and verified by simulations. Some analytic investigation on the communication overhead in the sensor networks is also provided. © 2006 IEEE

Wavelet-based burst system model change detection

A new scheme for detecting system burst changes is developed based on the continuous wavelet transform (CWT). The system is concisely represented by its time-frequency representation (TFR), the ratio of the CWTs of the output and the input. The TFR is first estimated, assuming that no system changes occur during a time period. A chi-square test is then executed to test the TFR estimate\u27s match to the data. System model changes are detected at the time samples when the assumption that the system is time invariant is broken. Simulations verify the capability of the proposed algorithm to detect burst system changes