Engineered microparticles based on drug–polymer coprecipitates for ocular-controlled delivery of Ciprofloxacin: influence of technological parameters

Abstract

Ciprofloxacin is a drug active against a broad spectrum of aerobic Gram-positive and Gram-negative bacteria, for the therapy of ocular infections. It requires frequent administrations owing to rapid ocular clearance and it is a good candidate for ocular controlled release formulations. The preparation of such drug release systems is still a challenge. Ionic interactions between ciprofloxacin and the polyelectrolytes chondroitin sulfate or lambda carrageenan result in coprecipitates that can act as microparticulate controlled release systems from which the drug is released after being displaced by the medium’s ions. In some formulations, Carbopol was added to improve the mucoadhesive properties. The aim of this research was the study of the influence of the technological parameters of the preparation method of coprecipitates on their particle size, with the goal of achieving particles engineered with a size suitable for the ocular administration. Technological parameters taken into account were: concentration of drug and polymer solutions utilized for the preparation of interaction products, possible use of surfactants (kind and concentration), temperature of the solutions and stirring during the process of preparation of the coprecipitates. Preliminary stability study tests were carried out to further characterize the leader formulation. Particle size in suspensions for ocular drug delivery is a critical parameter influencing the quality of the formulation. The results obtained from this study show that chondroitin sulfate coprecipitates present the best characteristics in terms of particle size suitable for ocular administration. A further improvement of the particle size characteristics has been obtained with the addition of surfactants.     

The SCD – Stem Cell Differentiation ESA Project: Preparatory Work for the Spaceflight Mission

Due to spaceflight, astronauts experience serious, weightlessness-induced bone loss because of an unbalanced process of bone remodeling that involves bone marrow mesenchymal stem cells (BMSCs), as well as osteoblasts, osteocytes, and osteoclasts. The effects of microgravity on osteo-cells have been extensively studied, but it is only recently that consideration has been given to the role of BMSCs. Previous researches indicated that human BMSCs cultured in simulated microgravity (sim-μg) alter their proliferation and differentiation. The spaceflight opportunities for biomedical experiments are rare and suffer from a number of operative constraints that could bias the validity of the experiment itself, but remain a unique opportunity to confirm and explain the effects due to microgravity, that are only partially activated/detectable in simulated conditions. For this reason, we carefully prepared the SCD – STEM CELLS DIFFERENTIATION experiment, selected by the European Space Agency (ESA) and now on the International Space Station (ISS). Here we present the preparatory studies performed on ground to adapt the project to the spaceflight constraints in terms of culture conditions, fixation and storage of human BMSCs in space aiming at satisfying the biological requirements mandatory to retrieve suitable samples for post-flight analyses. We expect to understand better the molecular mechanisms governing human BMSC growth and differentiation hoping to outline new countermeasures against astronaut bone loss.     

Cell-protection mechanism through autophagy in HGFs/<Emphasis Type="Italic">S. mitis</Emphasis> co-culture treated with Chitlac-nAg

Silver-based products have been proven to be effective in retarding and preventing bacterial growth since ancient times. In the field of restorative dentistry, the use of silver ions/nanoparticles has been explored to counteract bacterial infections, as silver can destroy bacterial cell walls by reacting with membrane proteins. However, it is also cytotoxic towards eukaryotic cells, which are capable of internalizing nanoparticles. In this work, we investigated the biological effects of Chitlac-nAg, a colloidal system based on a modified chitosan (Chitlac), administered for 24–48?h to a co-culture of primary human gingival fibroblasts and Streptococcus mitis in the presence of saliva, developed to mimic the microenvironment of the oral cavity. We sought to determine its efficiency to combat oral hygiene-related diseases without affecting eukaryotic cells. Cytotoxicity, reactive oxygen species production, apoptosis induction, nanoparticles uptake, and lysosome and autophagosome metabolism were evaluated. In vitro results show that Chitlac-nAg does not exert cytotoxic effects on human gingival fibroblasts, which seem to survive through a homoeostasis mechanism involving autophagy. That suggests that the novel biomaterial Chitlac-nAg could be a promising tool in the field of dentistry.     

Editorial: Special issue on approximate dynamic programming and reinforcement learning

We are extremely pleased to present this special issue of the Journal of Control Theory and Applications.Approximate dynamic programming (ADP) is a general and effective approach for solving optimal control and estimation problems by adapting to uncertain environments over time.ADP optimizes the sensing objectives accrued over a future time interval with respect to an adaptive control law,conditioned on prior knowledge of the system,its state,and uncertainties.A numerical search over the present value of the control minimizes a Hamilton-Jacobi-Bellman (HJB) equation providing a basis for real-time,approximate optimal control.     

A model-based approximate λ-policy iteration approach to online evasive path planning and the video game Ms. Pac-Man

This paper presents a model-based approximate λ-policy iteration approach using temporal differences for optimizing paths online for a pursuit-evasion problem, where an agent must visit several target positions within a region of interest while simultaneously avoiding one or more actively pursuing adversaries. This method is relevant to applications, such as robotic path planning, mobile-sensor applications, and path exposure. The methodology described utilizes cell decomposition to construct a decision tree and implements a temporal difference-based approximate λ-policy iteration to combine online learning with prior knowledge through modeling to achieve the objectives of minimizing the risk of being caught by an adversary and maximizing a reward associated with visiting target locations. Online learning and frequent decision tree updates allow the algorithm to quickly adapt to unexpected movements by the adversaries or dynamic environments. The approach is illustrated through a modified version of the video game Ms. Pac-Man, which is shown to be a benchmark example of the pursuit-evasion problem. The results show that the approach presented in this paper outperforms several other methods as well as most human players.     

Illustrative stream surfaces

Stream surfaces are an intuitive approach to represent 3D vector fields. In many cases, however, they are challenging objects to visualize and to understand, due to a high degree of self-occlusion. Despite the need for adequate rendering methods, little work has been done so far in this important research area. In this paper, we present an illustrative rendering strategy for stream surfaces. In our approach, we apply various rendering techniques, which are inspired by the traditional flow illustrations drawn by Dallmann and Abraham \& Shaw in the early 1980s. Among these techniques are contour lines and halftoning to show the overall surface shape. Flow direction as well as singularities on the stream surface are depicted by illustrative surface streamlines. ;To go beyond reproducing static text book images, we provide several interaction features, such as movable cuts and slabs allowing an interactive exploration of the flow and insights into subjacent structures, e.g., the inner windings of vortex breakdown bubbles. These methods take only the parameterized stream surface as input, require no further preprocessing, and can be freely combined by the user. We explain the design, GPU-implementation, and combination of the different illustrative rendering and interaction methods and demonstrate the potential of our approach by applying it to stream surfaces from various flow simulations. ;     

Understanding user requirements and preferences for a digital library Web portal

This article reports the findings of a user study conducted in the context of the TELplus project to gain insights about user needs and preferences for the digital library services offered by The European Library Web portal. The user requirements collection for the Web portal was designed by adopting a comprehensive survey approach. This combined explicit user feedback with implicit usage data so as to provide a more in-depth analysis of user experience with the portal. The analysis conducted shed light on likely motivations for both participant usage and reluctance to use the services provided, leading to more informed decisions on how to refine, improve, and present Web portal services to their future users. The lessons learnt from this case study also contributed to the development of an integrated methodological framework which provided insights for the future design and evaluation of digital library Web portals and services.     

Usability evaluation methods for the web: A systematic mapping study

Context

In recent years, many usability evaluation methods (UEMs) have been employed to evaluate Web applications. However, many of these applications still do not meet most customers’ usability expectations and many companies have folded as a result of not considering Web usability issues. No studies currently exist with regard to either the use of usability evaluation methods for the Web or the benefits they bring.

Objective

The objective of this paper is to summarize the current knowledge that is available as regards the usability evaluation methods (UEMs) that have been employed to evaluate Web applications over the last 14 years.

Method

A systematic mapping study was performed to assess the UEMs that have been used by researchers to evaluate Web applications and their relation to the Web development process. Systematic mapping studies are useful for categorizing and summarizing the existing information concerning a research question in an unbiased manner.

Results

The results show that around 39% of the papers reviewed reported the use of evaluation methods that had been specifically crafted for the Web. The results also show that the type of method most widely used was that of User Testing. The results identify several research gaps, such as the fact that around 90% of the studies applied evaluations during the implementation phase of the Web application development, which is the most costly phase in which to perform changes. A list of the UEMs that were found is also provided in order to guide novice usability practitioners.

Conclusions

From an initial set of 2703 papers, a total of 206 research papers were selected for the mapping study. The results obtained allowed us to reach conclusions concerning the state-of-the-art of UEMs for evaluating Web applications. This allowed us to identify several research gaps, which subsequently provided us with a framework in which new research activities can be more appropriately positioned, and from which useful information for novice usability practitioners can be extracted.     

To Score or Not to Score? Tripling Insights for Participatory Design

For evaluating visual-analytics tools, many studies confine to scoring user insights into data. For participatory design of those tools, we propose a three-level methodology to make more out of users' insights. The Relational Insight Organizer (RIO) helps to understand how insights emerge and build on one each other.