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.     

GraftFast Surface Engineering to Improve MOF Nanoparticles Furtiveness

Controlling the outer surface of nanometric metal–organic frameworks (nanoMOFs) and further understanding the in vivo effect of the coated material are crucial for the convenient biomedical applications of MOFs. However, in most studies, the surface modification protocol is often associated with significant toxicity and/or lack of selectivity. As an alternative, how the highly selective and general grafting GraftFast method leads, through a green and simple process, to the successful attachment of multifunctional biopolymers (polyethylene glycol (PEG) and hyaluronic acid) on the external surface of nanoMOFs is reported. In particular, effectively PEGylated iron trimesate MIL‐100(Fe) nanoparticles (NPs) exhibit suitable grafting stability and superior chemical and colloidal stability in different biofluids, while conserving full porosity and allowing the adsorption of bioactive molecules (cosmetic and antitumor agents). Furthermore, the nature of the MOF–PEG interaction is deeply investigated using high‐resolution soft X‐ray spectroscopy. Finally, a cell penetration study using the radio‐labeled antitumor agent gemcitabine monophosphate (³H‐GMP)‐loaded MIL‐100(Fe)@PEG NPs shows reduced macrophage phagocytosis, confirming a significant in vitro PEG furtiveness.     

Novel poly(etheraroyl-co-terephthal) hydrazides with liquid crystalline behaviour

Novel poly(etheraroyl-co-terephthal)hydrazides with liquid crystalline (LC) behaviour, synthesized by solution polycondensation followed by non-solvent coagulation in water, have been characterized by means of Fourier Transform infrared (FT-i.r.), differential scanning calorimetry (DSC) and wide angle X-ray scattering (WAXS) techniques. DSC thermograms and WAXS intensity profiles of as polymerized and coagulated homo- and copolymers are strongly dependent upon the molecular structure and constitution of the polymers: the poly(etheraroyl-hydrazide) homopolymer shows an LC behaviour and such a characteristic is maintained in copolymers with low content of terephthaloyldichloride comonomer, while a further increase in comonomer content attenuates this LC attitude. Annealing treatments on as polymerized and coagulated copolymers are able to transform the LC phase metastable at room temperature into crystalline and/or amorphous phases.     

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.