Nanoparticles for intestinal sepsis prevention synthesized via inverse miniemulsion polymerization

Previous research has shown that phosphate becomes depleted in the intestinal mucosa following local surgical injury or disease, triggering bacterial virulence and sepsis. Consequently, replenishment of depleted phosphate levels has been shown to prevent bacterial virulence in vitro[3] and sepsis in vivo[1]. Inverse phase miniemulsion polymerization (IPMP) has been extensively used in recent years in the production of nanocapsules for drug delivery of water-soluble therapeutic compounds that can be rendered degradable with time while allowing for sustained release of the encapsulated agent. In previous work we have successfully encapsulated inorganic phosphate salts, such as potassium monophosphate[2], into nanoparticles formed using IPMP. Our in vitro studies, however, have shown that polyphosphate salts, specifically sodium hexametaphosphate (PPi), are more effective at suppressing bacterial virulence[3]. This study focuses on the production and encapsulation of sodium hexametaphosphate into nanoparticles for controlled and extended release. Previous studies demonstrated[3] that encapsulation of sodium hexametaphosphate presents a series of challenges affecting the reproducibility of the IPMP process. Sodium hexametaphosphate is a strong lipophobe whose presence induces a high degree of order for water molecules. This modification in water structure weakens the surfactant interaction with water molecules, actively affecting the stability of the emulsion. This process, known as “salting-out”, has been shown to shift the hydrophilic-lipophilic balance (HLB) of nonionic surfactants towards a more lipophilic value[4]. While this issue has been addressed in a variety of previous studies, no mathematical correlation currently exists describing the effect of salt concentration on the HLB of a specific surfactant. Since miniemulsions require combinations of different phase-soluble surfactants, this adds to the complexity in predicting the extent and strength of the electrolyte effect on the stability of the emulsion system. In this study, we adjusted the IPMP process to counter the unstabilizing force created by the presence of sodium hexametaphosphate in the aqueous phase of the system. A precursor solution containing PEG diacrylate (PEGDA) macromer and NVP comonomer were chosen to create the hydrogel matrix, due to its biocompatibility and the ability to control the crosslinking density. The emulsion was formed of water in cyclohexane with the help of two nonionic surfactants, Tween 20 and SPAN 80. The effect of variations in HLB ranging from 4.0 to 9.5 on emulsion droplet size was investigated, for which the optimum overall HLB occurred at 6.5, an increase of two HLB points over the theoretical required value without salt interference[2, 3]. The effects of total surfactant amounts, reaction time, temperature and initiator concentration on nanoparticle yield were also explored. A final emulsion with 3.2% w/v of surfactants, 2 hours of reaction time, 64ºC and an initiator concentration equal to 1% of the initial double concentration resulted in a maximum nanoparticle mass yield of ~39%. Finally, the particles were characterized in terms of crosslink density, showing an efficient encapsulation of the studied salt and a promising path for in-vivo testing. This study helped us develop a reproduceable formulation of an IPMP process that yields stable nanoparticles with suitable therapeutic levels of phosphates. [1] Hyoju, S.K. et al, “Oral Polyphosphate Suppresses Bacterial Collagenase Production and Prevents Anastomotic Leak Due to Serratia marcescens and Pseudomonas aeruginosa”, Annals of Surgery, Feb, 2017. [2]Vadlamudi, S. et al., “Inverse miniemulsion polymerization of phosphate-loaded hydrogel nanoparticles for sepsis prevention”, Unpublished master dissertation, Illinois Institute of Technology, Chicago, Illinois (2014) [3] Yin Y et al, “De Novo Synthesis and Functional Analysis of Polyphosphate-Loaded Poly(Ethylene) Glycol Hydrogel Nanoparticles Targeting Pyocyanin and Pyoverdin Production in Pseudomonas aeruginosa as a Model Intestinal Pathogen”. Annals of Biomedical Engineering. 45(4):1058-1068, 2017. [4] Shinoda, K., & Takeda, H. “The effect of added salts in water on the hydrophile-lipophile balance of nonionic surfactants: The effect of added salts on the phase inversion temperature of emulsions”. Journal of Colloid And Interface Science, 32(4), 642–646, 1970

Aqueous Medium Management via Super Absorbent Materials

A super absorbent polymer material is contacted with an aqueous medium to absorb at least a portion of the aqueous medium. At least portion of the aqueous medium absorbed super absorbent material is subsequently regenerated to release water therefrom and to form a regenerated super absorbent material suitable for the contacting with a second quantity of an aqueous medium. Also disclosed are layered composites including an electrically conductive metal support layer, a layer of super absorbent material disposed thereon, and a layer of a selective semi-permeable material disposed adjacent the layer of the super absorbent material and spaced apart from the electrically conductive metal support layer.United States Paten

Modified Rubber Particles and Compositions Including the same

Modified scrap rubber particles, a method for forming the modified rubber particles and compositions including the modified rubber particles. The rubber particles are impregnated with at least one polymerizable monomer and polymerized to impregnate the rubber particles with a polymer. The impregnated polymer provides the modified rubber particles with improved properties which increase the potential uses for recycled scrap rubber. The modified rubber particles are useful in surface coatings, such as latex paint or powder coatings and can be used as a soil substitute.Sponsorship: Illinois Institute of TechnologyUnited States Paten

Control of complex distributed systems with distributed intelligent agents

Control of spatially distributed systems is a challenging problem because of their complex nature, nonlinearity, and generally high order. The lack of accurate and computationally efficient model-based techniques for large, spatially distributed systems leads to challenges in controlling the system. Agent-based control structures provide a powerful tool to manago distributed systems by utilizing (organizing) local and global information obtained from the system. A hierarchical, agent-based system with local and global controller agents is developed to control networks of interconnected chemical reactors (CSTRs). The global controller agent dynamically updates local controller agent's objectives as the reactor network conditions change. One challenge posed is control of the spatial distribution of autocatalytic species in a network of reactors hosting multiple species. The multi-agent control system is able to intelligently manipulate the network flow rates such that the desired spatial distribution of species is achieved. Furthermore, the robustness and flexibility of the agent-based control system is illustrated through examples of disturbance rejection and scalability with respect to the size of the network.Endnote format citation for DOI:10.1016/j.jprocont.2006.06.00

Interpenetrated Rubber Particles and Compositions Including the Same

Modified scrap rubber particles, a method for forming the modified rubber particles and compositions including the modified rubber particles. The rubber particles are impregnated with at least one polymerizable monomer and polymerized to impregnate the rubber particles with a polymer. The impregnated polymer provides the modified rubber particles with improved properties which increase the potential uses for recycled scrap rubber. The modified rubber particles are useful in surface coatings, such as latex paint or powder coatings and can be used as a soil substitute.Sponsorship: Illinois Institute of TechnologyUnited States Paten

Statistical Monitoring of Complex Chemical Processes Using Agent-Based Systems

It is highly desirable to have a statistical process monitoring (SPM) system that detects the abnormalities in process operations quickly with as few missed and false alarms as possible while the process operates under various operating conditions An agent-based combined monitoring and fault detection framework is proposed in this study. In this framework, different SPM techniques compete with and complement each other to enhance detection speed and accuracy. SPM techniques from literature such as principal component analysis (PCA), multiblock PCA (MBPCA), and dynamic PCA (DPCA) techniques are implemented in this agent-based process supervision system An agent performance assessment and agent management layer provides dynamic adaptation of the supervision system and improves the performance of SPM The statistical information coming from each of the statistical techniques is summarized through a consensus mechanism The performance of the agent-based consensus mechanism using different consensus criteria is tested for system disturbances of various magnitudes The effectiveness of the proposed agent-based framework with different consensus criteria is evaluated based on fault detection times and missed alarm rates and the adaptation of the supervision system is illustratedEndnote format citation for DOI:10.1021/ie901368

Effect of Asymmetric Manipulations in Autocatalytic Networks

In this paper, we show that heterogeneous networks can be configured and reconfigured to operate in flexible spatial patterns The concept is demonstrated by using a square grid of continuous stirred tank reactors with nearest neighbor interactions and hosting multiple cubic autocatalytic species Asymmetry is introduced in the system by allowing for different feed flow rates in the reactors. A heterogeneous system offers expanded phase space, improved stability. and coexistence characteristics The advantages of asymmetry are studied using bifurcation diagrams, continuation studies. and dynamicsEndnote format citation for DOI:10.1021/ie901096

Control of grade transitions in distributed chemical reactor networks - An agent-based approach

Supervision of distributed manufacturing processes producing different grades of a product requires intelligent reconfiguration strategies during grade transition phases to minimize off-spec production. Agent-based approaches are ideal for such problems and they provide flexible, robust, and emergent solutions during dynamically changing process conditions. Three different multi-layered multi-agent, frameworks are proposed for the supervision of grade transitions in autocatalytic reactor networks. The first framework is the centralized framework and it is useful for small-scale grade transitions where only a small region of the network needs to be reconfigured. Alternatively, the other two frameworks use a decentralized approach. The first decentralized framework implements genetic algorithms and the second one uses self-organizing heuristics and auctions for large-scale grade transitions. The case studies demonstrate that as the complexity of the reconfiguration problem increases, decentralized solutions perform more efficiently.Endnote format citation for DOI:10.1016/j.compchemeng.2008.02.00