A water-soluble,mucoadhesive quaternary ammonium chitosan-methyl-β-cyclodextrin conjugate forming inclusion complexes with dexamethasone

The ocular bioavailability of lipophilic drugs, such as dexamethasone, depends on both drug water solubility and mucoadhesion/permeation. Cyclodextrins and chitosan are frequently employed to either improve drug solubility or prolong drug contact onto mucosae, respectively. Although the covalent conjugation of cyclodextrin and chitosan brings to mucoadhesive drug complexes, their water solubility is restricted to acidic pHs. This paper describes a straightforward grafting of methyl-β-cyclodextrin (MCD) on quaternary ammonium chitosan (QA-Ch60), mediated by hexamethylene diisocyanate. The resulting product is a water-soluble chitosan derivative, having a 10-atom long spacer between the quaternized chitosan and the cyclodextrin. The derivative is capable of complexing the model drug dexamethasone and stable complexes were also observed for the lyophilized products. Furthermore, the conjugate preserves the mucoadhesive properties typical of quaternized chitosan and its safety as solubilizing excipient for ophthalmic applications was preliminary assessed by in vitro cytotoxicity evaluations. Taken as a whole, the observed features appear promising for future processing of the developed product into 3D solid forms, such as controlled drug delivery systems, films or drug eluting medical devices.

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Combining customer needs and the customer’s way of using the product to set customer-focused targets in the House of Quality

An increasing number of products are equipped with software and sensors. This suggests that, in order to deliver more customised performance, future products will be developed to accommodate systems that supply information on how these products are used. Today, information on the customer’s way of using a product is seldom factored into product design, but the opportunities for making use of it are increasing dramatically due to the amount of available data that can be logged. The proposed methodology is to formulate Customer Needs at a detailed level to be able to link customer satisfaction with a clear interface to the Design Requirements. These links are obtained by combining information acquired by means of surveys, among other methodologies, as well as usage data from customer products. The method is based on the planning House of Quality and also takes cost and risk into consideration. Risk is estimated using the Analytical Hierarchy Process, whereby a hierarchy of the most relevant customer information is constructed to make designers aware of how customer-focused the design process is. To validate the proposed methodology an illustrative example is presented. Results show that the method provides valuable information that enables the company to remain customer-focused during the whole process but also when strategic decisions on price and product launch are made.     

Design and characteristics of gellan gum beads for modified release of meloxicam

The aim of the presented work was to design, formulate and evaluate the properties of low-acyl gellan macro beads with the potential application as carriers for oral delivery of meloxicam (MLX) in the prophylaxis of colorectal cancer. The beads were obtained by means of ionotropic gelation technique. Calcium chloride (1.0%, 9.0?×?10^?2 M) was used as the cross-linking agent. Nine different polymer, drug and surfactant (Tween^®80) mixtures were used for production of the beads. The quantitative compositions of the mixtures were generated with the application of the Design of Experiments (DoE) modulus from the STATISTICA Software. The prepared formulations revealed 7.2–27.0% of drug loading and 29.2–50.7% drug encapsulation efficiency. It turned out that 0.5% amount of gellan gum in the mixtures was not sufficient to obtain spherical beads. The morphology and surface of the dried beads were analyzed by SEM. Raman spectra confirmed that MLX did not undergo structural changes during production of the beads. The swelling behavior and degradation of the beads were evaluated in three simulated gastrointestinal fluids at different pH (1.2; 4.5; 6.8). The MLX in vitro release studies were conducted on USP apparatus IV, working in the open loop mode. The obtained results showed that MLX release from the dried beads was pH-dependent. The formulations obtained from mixtures containing 1.0 and 1.5% of gellan may be considered as oral dosage forms for MLX, intended to omit the stomach and release the drug in the distal parts of the gastrointestinal tract.     

Dry powders for the inhalation of ciprofloxacin or levofloxacin combined with a mucolytic agent for cystic fibrosis patients

Objective: This study aimed to design and characterize an inhalable dry powder of ciprofloxacin or levofloxacin combined with the mucolytics acetylcysteine and dornase alfa for the management of pulmonary infections in patients with cystic fibrosis.

Methods: Ball milling, homogenization in isopropyl alcohol and spray drying processes were used to prepare dry powders for inhalation. Physico-chemical characteristics of the dry powders were assessed via thermogravimetric analysis, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometry and scanning electron microscopy. The particle size distribution, dissolution rate and permeability across Calu-3 cell monolayers were analyzed. The aerodynamic parameters of dry powders were determined using the Andersen cascade impactor (ACI).

Results: After the micronization process, the particle sizes of the raw materials significantly decreased. X-ray and DSC results indicated that although ciprofloxacin showed no changes in its crystal structure, the structure of levofloxacin became amorphous after the micronization process. FT-IR spectra exhibited the characteristic peaks for ciprofloxacin and levofloxacin in all formulations. The dissolution rates of micro-homogenized and spray-dried ciprofloxacin were higher than that of untreated ciprofloxacin. ACI results showed that all formulations had a mass median aerodynamic diameter less than 5?μm; however, levofloxacin microparticles showed higher respirability than ciprofloxacin powders did. The permeability of levofloxacin was higher than those of the ciprofloxacin formulations.

Conclusion: Together, our study showed that these methods could suitably characterize antibiotic and mucolytic-containing dry powder inhalers.     

Ratiometric Nanothermometer Based on a Radical Excimer for In Vivo Sensing (Small 32/2023)

Ratiometric fluorescent nanothermometers with near-infrared emission play an important role in in vivo sensing since they can be used as intracellular thermal sensing probes with high spatial resolution and high sensitivity, to investigate cellular functions of interest in diagnosis and therapy, where current approaches are not effective. Herein, the temperature-dependent fluorescence of organic nanoparticles is designed, synthesized, and studied based on the dual emission, generated by monomer and excimer species, of the tris(2,4,6-trichlorophenyl)methyl radical (TTM) doping organic nanoparticles (TTMd-ONPs), made of optically neutral tris(2,4,6-trichlorophenyl)methane (TTM-αH), acting as a matrix. The excimer emission intensity of TTMd-ONPs decreases with increasing temperatures whereas the monomer emission is almost independent and can be used as an internal reference. TTMd-ONPs show a great temperature sensitivity (3.4% K⁻¹ at 328 K) and a wide temperature response at ambient conditions with excellent reversibility and high colloidal stability. In addition, TTMd-ONPs are not cytotoxic and their ratiometric outputs are unaffected by changes in the environment. Individual TTMd-ONPs are able to sense temperature changes at the nano-microscale. In vivo thermometry experiments in Caenorhabditis elegans (C. elegans) worms show that TTMd-ONPs can locally monitor internal body temperature changes with spatio-temporal resolution and high sensitivity, offering multiple applications in the biological nanothermometry field.     

Ockham’s index of citation impact

Scientometrics - We demonstrate that by using a triple of simple numerical summaries: an author’s productivity, their overall impact, and a single other bibliometric index that aims to...     

Investigation on the effect of NiO content on spray deposited ZnO for selective ammonia detection

Journal of Materials Science: Materials in Electronics - Zinc Oxide/Nickel Oxide (ZnO/NiO) heterostructures were deposited using the spray pyrolysis technique by varying NiO content. The X-ray...     

Accelerated multiobjective design of miniaturized microwave components by means of nested kriging surrogates

Design of microwave components is an inherently multiobjective task. Often, the objectives are at least partially conflicting and the designer has to work out a suitable compromise. In practice, generating the best possible trade‐off designs requires multiobjective optimization, which is a computationally demanding task. If the structure of interest is evaluated through full‐wave electromagnetic (EM) analysis, the employment of widely used population‐based metaheuristics algorithms may become prohibitive in computational terms. This is a common situation for miniaturized components, where considerable cross‐coupling effects make traditional representations (eg, network equivalents) grossly inaccurate. This article presents a framework for accelerated EM‐driven multiobjective design of compact microwave devices. It adopts a recently reported nested kriging methodology to identify the parameter space region containing the Pareto front and to render a fast surrogate, subsequently used to find the first approximation of the Pareto set. The final trade‐off designs are produced in a separate, surrogate‐assisted refinement process. Our approach is demonstrated using a three‐section impedance matching transformer designed for the best matching and the minimum footprint area. The Pareto set is generated at the cost of only a few hundred of high‐fidelity EM simulations of the transformer circuit despite a large number of geometry parameters involved.     

Surrogate modeling of impedance matching transformers by means of variable‐fidelity electromagnetic simulations and nested cokriging

Accurate performance evaluation of microwave components can be carried out using full‐wave electromagnetic (EM) simulation tools, routinely employed for circuit verification but also in the design process itself. Unfortunately, the computational cost of EM‐driven design may be high. This is especially pertinent to tasks entailing considerable number of simulations (eg, parametric optimization, statistical analysis). A possible way of alleviating these difficulties is utilization of fast replacement models, also referred to as surrogates. Notwithstanding, conventional modeling methods exhibit serious limitations when it comes to handling microwave components. The principal challenges include large number of geometry and material parameters, highly nonlinear characteristics, as well as the necessity of covering wide ranges of operating conditions. The latter is mandatory from the point of view of the surrogate model utility. This article presents a novel modeling approach that incorporates variable‐fidelity EM simulations into the recently reported nested kriging framework. A combination of domain confinement due to nested kriging, and low‐/high‐fidelity EM data blending through cokriging, enables the construction of reliable surrogates at a fraction of cost required by single‐fidelity nested kriging. Our technique is validated using a three‐section miniaturized impedance matching transformer with its surrogate model rendered over wide range of operating frequencies. Comprehensive benchmarking demonstrates superiority of the proposed method over both conventional models and nested kriging.