pH-sensitive nano-polyelectrolyte complexes with arthritic macrophage-targeting delivery of triptolide.

Since pro-inflammatory macrophages take on a critical significance in the pathophysiology of rheumatoid arthritis (RA), the therapeutics to affect macrophages may receive distinct anti-RA effects. However, the therapeutic outcomes are still significantly impeded, which is primarily due to the insufficient drug delivery at the arthritic site. In this study, the macrophage-targeting and pH stimuli-responsive nano-polyelectrolyte complexes were designed for the efficient targeted delivery of triptolide (TP/PNPs) on the arthritic site. The anionic and cationic amphiphilic copolymers, i.e., hyaluronic acid-g-vitamin E succinate (HA-VE) and the quaternized poly (ß-amino ester) (QPBAE-C18), were prepared and then characterized. The result indicated that TP/PNPs with the uniform particle size of âˆ¼ 175 nm exhibited the high drug loading capacity and storage stability based on the polymeric charge interaction, in which DLC and DEE of TP/PNPs were obtained as 11.27 ± 0.44 % and 95.23 ± 2.34 %, respectively. Mediated by the "ELVIS" effect of NPs, CD44 receptor-mediated macrophage targeting, and pH-sensitive endo/lysosomal escape under the "proton sponge" effect, TP/PNPs exhibited the enhanced cellular internalization and cytotoxicity while mitigating the inflammation of LPS-activated RAW 264.7 cells. Even after 96-hour after administration, PNPs were preferentially accumulated in the inflammatory joints in a long term. It is noteworthy that after treatment for 14 days with 100 µg/kg of TP, TP/PNPs significantly facilitated arthritic symptom remission, protected cartilage, and mitigated inflammation of antigen-induced arthritis (AIA) rats, whereas the systematic side-effects of TP were reduced. In this study, an effective drug delivery strategy was proposed for the treatment of RA.

Control and estimation of maximum gas pressure below landfill cover with horizontal gas wells: Analytical study.

Horizontal spacing of horizontal extraction gas wells can be designed to achieve a 90% pumping rate of the total generated landfill gas (LFG) from given waste properties (viz: gas permeability, landfill gas generation and non-homogeneity with depth), cover characteristics and vacuum pressure. However, cover characteristics and vacuum pressure are also important design parameters and different combinations of them result in different distributions of gas pressure in the waste, some of which would induce problematic air intrusion while others might pose threat to cover stability. This paper uses the maximum gas pressure directly below cover to distinguish these combinations, and provides the first study of the effects of the above parameters on potential outcomes. The ability of the overlying cover to resist LFG emission from the landfilled waste is suggested not to exceed a critical value, otherwise the maximum gas pressure below it would become at least 1 kPa larger than atmospheric pressure. A design formula for this critical value is proposed with respect to typical values of waste properties, vacuum pressure and the buried depth of horizontal wells in wide ranges. Together with consideration of recovery efficiency, the proposed method can be used to design a horizontal extraction gas collection system and a cover system in better working condition, and to evaluate the maximum gas pressure below cover. These applications are illustrated by a worked example.

Design of horizontal landfill gas collection wells in non-homogeneous landfills.

Considering exponential decreases in gas permeability and gas generation of waste with depth, a two-dimensional analytical model is developed to describe the landfill gas (LFG) recovery using horizontal wells. This model is used to simulate more than 680,000 scenarios involving typical values of waste properties, cover characteristics and design parameters for horizontal wells (seven variables in total). The coupled effect of these seven variables on air intrusion and the gas recovery efficiency of horizontal wells are investigated. It is shown that all the variables examined, except for the two variables defining waste non-homogeneity, could be integrated into three dimensionless variables. The horizontal spacing and buried depth of horizontal wells are examined as a function of cover characteristics, waste properties, and vacuum pressure to allow the development of a generalized design method for horizontal wells. An upper limit of horizontal well spacing is defined (for an 85% recovery rate) and a simple formula is provided which can be used to estimate the corresponding level of air intrusion. The upper limit spacing is shown to be affected by the non-homogeneity in gas permeability of waste, cover characteristics, and buried well depth. Using a worked example, the proposed method is shown to be capable of estimating air intrusion into existing horizontal gas collection wells and to optimize the design of horizontal wells considering waste non-homogeneity.

Recovery response of vertical gas wells in non-homogeneous landfills.

A two-dimensional axisymmetric and normalized analytical model for landfill gas (LFG) migration around a vertical well is developed. The vertical gas permeability and LFG generation rate of waste are assumed to be subject to exponential decreases with depth. Using a general analytical solution, over 500,000 scenarios involving a combination of typical control variables (viz: cover properties, waste properties, vacuum pressure, well radius and spacing) are modelled. A quantitative analysis of the coupled effects of these control variables on LFG recovery rate indicates that the recovery response could be captured by: (a) three dimensionless variables (denoted as cover resistance, pump capacity, and well spacing parameters), and (b) two constants defining the decreases in gas permeability and LFG generation of waste with depth. For example, if the LFG generation rate of the waste at the top is doubled, a two times increase in the vacuum pressure with other parameters being equal would give a same gas recovery rate, as well as simultaneously doubling the thickness and gas permeability of the cover. The recovery efficiency of a vertical well with a low permeability cover is examined as a function of cover resistance and pump capacity, and design charts are presented that may be used to optimize gas recovery by adjusting cover properties and vacuum pressure. The proposed model makes it possible to consider the waste non-homogeneity in the design process, and the results contribute to a preliminary design of a cover and vertical LFG collection systems.

Design of vertical landfill gas collection wells considering non-homogeneity with depth.

Considering variable gas permeability and gas generation of waste with depth, different combinations of cover properties, vacuum pressure, and horizontal spacing of vertical wells giving rise to a 90% gas recovery rate are identified for typical waste properties. The effects of passive and active gas collection on horizontal well spacing are quantified. The normalized well spacing for 90% recovery is examined as a function of the cover resistance and the vacuum pump capacity. Design charts dependent on changes in gas permeability and gas generation rate with depth are presented to aid in the design of vertical gas wells. It is demonstrated that the non-homogeneity in gas permeability of waste is of great importance. For a conservative design, uncertainty in the non-homogeneity in gas permeability should be overestimated while uncertainty with respect to the non-homogeneity in LFG generation should generally be underestimated. The use of the proposed method for the design of the spacing of vertical gas wells in a situation with waste non-homogeneity is illustrated by a practical example.

A gas flow model for layered landfills with vertical extraction wells.

This paper developed a two-dimensional axisymmetric analytical model for layered landfills with vertical wells. The model uses a horizontal layered structure to describe the waste non-homogeneity with depth in gas generation, permeability and temperature. The governing equations in the cylindrical coordinate system were transformed to dimensionless forms and solved using a method of eigenfunction expansion. After verification, the effects of different well boundary conditions and gas extraction systems on recovery efficiency were investigated. A dimensionless double-layer system, consisting of a cover and a waste layer, was also explored. The results show that a constant vacuum pressure boundary condition can be enough to describe a perforated pipe surrounded by drainage gravel with a reasonable value of well radius, such as half the radius of gravel fill. Also, the 7 independent variables (one marked with an asterisk is dimensionless) of a double-layer system can be integrated into 3 dimensionless ones: Cover permeability Kv1∗/(Vertical gas permeability of waste Kv2∗×Cover thickness h1∗),-Vacuum pressure pw×PatmKv2∗/(µRgT2×Gas generation rate of waste s2) and ln(Well radius rw∗)/(Anisotropy degree of waste k2∗). The integration is based on the inherent mechanism of this flow system with certain simplification. The effects of these variables are then quantitatively characterized for a better understanding of gas recovery efficiency. Same recovery efficiency can be achieved with different variable combinations. For example, increasing h1∗ (such as doubling it) has the same effect with decreasing Kv1∗ (such as halving it). Along with the reduction of variables by half, the integration can facilitate the preliminary design, and is a small but important advance in the consideration of MSW non-homogeneity.