Forced Wetting Properties of Bacteria-Laden Droplets Experiencing Initial Evaporation.

Microbial adhesion and spreading on surfaces are crucial aspects in environmental and industrial settings being also the early stage of complex surface-attached microbial communities known as biofilms. In this work, Pseudomonas fluorescens-laden droplets on hydrophilic substrates (glass coupons) are allowed to partially evaporate before running wetting measurements, to study the effect of evaporation on their interfacial behavior during spillover or splashing. Forced wetting is investigated by imposing controlled centrifugal forces, using a novel rotatory device (Kerberos). At a defined evaporation time, results for the critical tangential force required for the inception of sliding are presented. Microbe-laden droplets exhibit different wetting/spreading properties as a function of the imposed evaporation times. It is found that evaporation is slowed down in bacterial droplets with respect to nutrient medium ones. After sufficient drying times, bacteria accumulate at droplet edges, affecting the droplet shape and thus depinning during forced wetting tests. Droplet rear part does not pin during the rotation test, while only the front part advances and spreads along the force direction. Quantitative results obtained from the well-known Furmidge's equation reveal that force for sliding inception increases as evaporation time increases. This study can be of support for control of biofilm contamination and removal and possible design of antimicrobial/antibiofouling surfaces.

Structure Identification of Adsorbed Anionic-Nonionic Binary Surfactant Layers Based on Interfacial Shear Rheology Studies and Surface Tension Isotherms.

Mixtures of anionic sodium oleate (NaOl) and nonionic ethoxylated or alkoxylated surfactants improve the selective separation of magnesite particles from mineral ores during the process of flotation. Apart from triggering the hydrophobicity of magnesite particles, these surfactant molecules adsorb to the air-liquid interface of flotation bubbles, changing the interfacial properties and thus affecting the flotation efficiency. The structure of adsorbed surfactants layers at the air-liquid interface depends on the adsorption kinetics of each surfactant and the reformation of intermolecular forces upon mixing. Up to now, researchers use surface tension measurements to understand the nature of intermolecular interactions in such binary surfactant mixtures. Aiming to adapt better to the dynamic character of flotation, the present work explores the interfacial rheology of NaOl mixtures with different nonionic surfactants to study the interfacial arrangement and viscoelastic properties of adsorbed surfactants under the application of shear forces. Interfacial shear viscosity results reveal the tendency on nonionic molecules to displace NaOl molecules from the interface. The critical nonionic surfactant concentration needed to complete NaOl displacement at the interface depends on the length of its hydrophilic part and on the geometry of its hydrophobic chain. The above indications are supported by surface tension isotherms.

Wetting and Imbibition Characteristics of Pseudomonas fluorescens Biofilms Grown on Stainless Steel.

This study aims to provide insights into biofilm resistance associated with their structural properties acquired during formation and development. On this account, the wetting and imbibition behavior of dehydrated Pseudomonas fluorescens biofilms grown on stainless steel electropolished substrates is thoroughly examined at different biofilm ages. A polar liquid (water) and a non-polar liquid (diiodomethane) are employed as wetting agents in the form of sessile droplets. A mathematical model is applied to appraise the wetting and imbibition performance of biofilms incorporating the evaporation of sessile droplets. The present results show that the examined biofilms are hydrophilic. The progressive growth of biofilms leads to a gradual increase of substrate surface coverage─up to full coverage─accompanied by a gradual decrease of biofilm surface roughness. It is noteworthy that just after 24 h of biofilm growth, the surface roughness increases about 6.7 times the roughness of the clean stainless steel surface. It is further found that the imbibition of liquid in the biofilm matrix is restricted only to the biofilm region under the sessile droplet. The lack of further capillary imbibition into the biofilm structure, beyond the droplet deposition region, implies that the biofilm matrix is not in the form of an extended network of interconnected micro/nanopores. All in all, the present results indicate a resilient biofilm structure to biocide penetration despite its hydrophilic nature.

Branched Poly(ε-caprolactone)-Based Copolyesters of Different Architectures and Their Use in the Preparation of Anticancer Drug-Loaded Nanoparticles.

Limitations associated with the use of linear biodegradable polyesters in the preparation of anticancer nano-based drug delivery systems (nanoDDS) have turned scientific attention to the utilization of branched-chain (co-)polymers. In this context, the present study evaluates the use of novel branched poly(ε-caprolactone) (PCL)-based copolymers of different architectures for the preparation of anticancer nanoparticle (NP)-based formulations, using paclitaxel (PTX) as a model drug. Specifically, three PCL-polyol branched polyesters, namely, a three-arm copolymer based on glycerol (PCL-GLY), a four-arm copolymer based on pentaerythritol (PCL-PE), and a five-arm copolymer based on xylitol (PCL-XYL), were synthesized via ring-opening polymerization and characterized by proton nuclear magnetic resonance (1H-NMR), gel permeation chromatography (GPC), intrinsic viscosity, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier-transform infrared (FT-IR) spectroscopy and cytotoxicity. Then, PTX-loaded NPs were prepared by an oil-in-water emulsion. The size of the obtained NPs varied from 200 to 300 nm, while the drug was dispersed in crystalline form in all formulations. High encapsulation efficiency and high yields were obtained in all cases, while FTIR analysis showed no molecular drug polymer. Finally, in vitro drug release studies showed that the studied nanocarriers significantly enhanced the dissolution rate and extent of the drug.

Wetting of Dehydrated Hydrophilic Pseudomonas fluorescens Biofilms under the Action of External Body Forces.

Wetting of dehydrated Pseudomonas fluorescens biofilms grown on glass substrates by an external liquid is employed as a means to investigate the complex morphology of these biofilms along with their capability to interact with external fluids. The porous structure left behind after dehydration induces interesting droplet spreading on the external surface and imbibition into pores upon wetting. Static contact angles and volume loss by imbibition measured right upon droplet deposition indicate that biofilms of higher incubation times show a higher porosity and effective hydrophilicity. Furthermore, during subsequent rotation tests, using Kerberos device, these properties dictate a peculiar forced wetting/spreading behavior. As rotation speed increases a long liquid tail forms progressively at the rear part of the droplet, which stays pinned at all times, while only the front part of the droplet depins and spreads. Interestingly, the experimentally determined retention force for the onset of droplet sliding on biofilm external surface is lower than that on pure glass. An effort is made to describe such complex forced wetting phenomena by presenting apparent contact angles, droplet length, droplet shape contours, and edges position as obtained from detailed image analysis.

Reliable fluid-mechanical characterization of haemofilters: Addressing the deficiencies of current standards and practices.

Facile methods for accurate fluid-mechanical characterization of haemofilters (HF) are indispensable for haemofiltration process improvements, equipment design/optimization, and reliable module specifications. Currently employed methods, implemented through specific experimental in vitro protocols, are assessed herein in detail, considering the conditions prevailing during haemofiltration. Minimum number of key parameters required to fully describe the common countercurrent flow field, in the HF active section, include membrane permeance K and friction coefficients in lumen and shell side (ff and fs ). It is shown that the countercurrent flow mode itself is incapable of yielding these parameters, based on externally measured flow rates and pressures. Similarly, the relevant ISO protocol is deficient as it can only provide rough underpredictions of permeance K. The causes of such inherent deficiencies of current standards and practices are analyzed. In contrast, a recently developed methodology, accounting for the (heretofore ignored) pressure drop in module headers and combining a mechanistic theoretical model with experimental data from 2 special haemofilter operating modes, yields an accurate determination of the key parameters (K, ff , fs ). Additionally, it permits a full description of flow field for Newtonian liquids, for both constant and axially varying viscosity in fiber-lumen due to the transmembrane flux. Development of new reliable standards is suggested, facilitated by the insights gained in this work.

On kinetic modelling for solar redox thermochemical H2O and CO2 splitting over NiFe2O4 for H2, CO and syngas production.

This study aims at developing a kinetic model that can adequately describe solar thermochemical water and carbon dioxide splitting with nickel ferrite powder as the active redox material. The kinetic parameters of water splitting of a previous study are revised to include transition times and new kinetic parameters for carbon dioxide splitting are developed. The computational results show a satisfactory agreement with experimental data and continuous multicycle operation under varying operating conditions is simulated. Different test cases are explored in order to improve the product yield. At first a parametric analysis is conducted, investigating the appropriate duration of the oxidation and the thermal reduction step that maximizes the hydrogen yield. Subsequently, a non-isothermal oxidation step is simulated and proven as an interesting option for increasing the hydrogen production. The kinetic model is adapted to simulate the production yields in structured solar reactor components, i.e. extruded monolithic structures, as well.

Cyclin and DNA distributed cell cycle model for GS-NS0 cells.

Mammalian cell cultures are intrinsically heterogeneous at different scales (molecular to bioreactor). The cell cycle is at the centre of capturing heterogeneity since it plays a critical role in the growth, death, and productivity of mammalian cell cultures. Current cell cycle models use biological variables (mass/volume/age) that are non-mechanistic, and difficult to experimentally determine, to describe cell cycle transition and capture culture heterogeneity. To address this problem, cyclins-key molecules that regulate cell cycle transition-have been utilized. Herein, a novel integrated experimental-modelling platform is presented whereby experimental quantification of key cell cycle metrics (cell cycle timings, cell cycle fractions, and cyclin expression determined by flow cytometry) is used to develop a cyclin and DNA distributed model for the industrially relevant cell line, GS-NS0. Cyclins/DNA synthesis rates were linked to stimulatory/inhibitory factors in the culture medium, which ultimately affect cell growth. Cell antibody productivity was characterized using cell cycle-specific production rates. The solution method delivered fast computational time that renders the model's use suitable for model-based applications. Model structure was studied by global sensitivity analysis (GSA), which identified parameters with a significant effect on the model output, followed by re-estimation of its significant parameters from a control set of batch experiments. A good model fit to the experimental data, both at the cell cycle and viable cell density levels, was observed. The cell population heterogeneity of disturbed (after cell arrest) and undisturbed cell growth was captured proving the versatility of the modelling approach. Cell cycle models able to capture population heterogeneity facilitate in depth understanding of these complex systems and enable systematic formulation of culture strategies to improve growth and productivity. It is envisaged that this modelling approach will pave the model-based development of industrial cell lines and clinical studies.

Enhanced Frying Efficiency at Low Temperatures Utilizing a Novel Planetary Fryer.

This study aims to optimize the frying process of natural porous materials (like potatoes) by enhancing heat and mass transfer phenomena through significant horizontal acceleration values following a spatially periodic pattern that alternates the intensity of inertia forces uniformly across the frying vessel. The generated horizontal inertial forces act complementary to the normal vertical buoyancy force for the creation of agitating convective currents in the oil and for vapor bubbles' departure from the surface of frying objects. The use of an innovative frying device, employing simultaneous rotation around two vertical axes at a different speed in a so-called planetary type of motion, serves to facilitate this production of horizontal acceleration values that allows intensifying the performance of frying. The present investigation examines the impact of rotational speed, along with oil temperature and frying duration, on the water loss and sensory evaluation of fried items. The potato-to-oil ratios typically found in industrial frying operations are employed. The intended outcome is a more energy-efficient frying process, reduced cooking times, and a healthier product due to lower frying temperatures and the consequent decreased formation of harmful compounds. This approach carries substantial implications for food processing, potentially enhancing productivity while limiting operational costs.

Is frying possible in space?

Dietary nutrition and uptake of earth-like foods are extremely important aspects for the health and performance of astronauts, especially during future planned long-term space missions. Despite the major progress in studying and designing systems for crop cultivation in microgravity conditions in the last years, there hasn't been equal interest in food preparation processes and cooking. There are several reasons for this but it is chiefly because at present astronauts stay in space for a few months at most, so there is no serious nutritional or psychological need for earth-like food habits. This, however, will change drastically in long-term missions, e.g., to Moon and Mars. French fries are a very popular food commodity across many cultural backgrounds on earth and as such they may be appreciated by long-term space travelers of different origin. The process of frying in hot oil is associated with complex heat and mass transfer along with the growth and detachment of water vapor bubbles. These phenomena are strongly affected by buoyancy and gravitational acceleration making the study of frying at space conditions a challenging task. The present work examines potato frying in hot oil during the short duration low gravity conditions achieved in a Parabolic Flight Campaign organized by the European Space Agency. An innovative device has been constructed, allowing the simultaneous observation of bubbles dynamics above the potato surface and the thermal behavior inside the potato flesh. It is seen that even in the absence of buoyancy i.e., during parabolas, vapor bubbles still detach and depart from the surface of potato permitting hot oil to maintain contact with the potato surface and leading eventually to a fried product. Instantaneous overpressure inside potato pores due to vapor formation upon boiling of potato water is suggested as the mechanism generating the force for bubbles detachment and departure. Moreover, the amount of produced vapor is comparable among the examined values of gravitational acceleration, including the low gravity conditions during parabolas. All in all, the results of the present study provide primary experimental evidence that frying can occur in space.

Migration of surface-associated microbial communities in spaceflight habitats.

Astronauts are spending longer periods locked up in ships or stations for scientific and exploration spatial missions. The International Space Station (ISS) has been inhabited continuously for more than 20 years and the duration of space stays by crews could lengthen with the objectives of human presence on the moon and Mars. If the environment of these space habitats is designed for the comfort of astronauts, it is also conducive to other forms of life such as embarked microorganisms. The latter, most often associated with surfaces in the form of biofilm, have been implicated in significant degradation of the functionality of pieces of equipment in space habitats. The most recent research suggests that microgravity could increase the persistence, resistance and virulence of pathogenic microorganisms detected in these communities, endangering the health of astronauts and potentially jeopardizing long-duration manned missions. In this review, we describe the mechanisms and dynamics of installation and propagation of these microbial communities associated with surfaces (spatial migration), as well as long-term processes of adaptation and evolution in these extreme environments (phenotypic and genetic migration), with special reference to human health. We also discuss the means of control envisaged to allow a lasting cohabitation between these vibrant microscopic passengers and the astronauts.

Mass Transfer Characteristics of Haemofiltration Modules-Experiments and Modeling.

Reliable mathematical models are important tools for design/optimization of haemo-filtration modules. For a specific module, such a model requires knowledge of fluid- mechanical and mass transfer parameters, which have to be determined through experimental data representative of the usual countercurrent operation. Attempting to determine all these parameters, through measured/external flow-rates and pressures, combined with the inherent inaccuracies of pressure measurements, creates an ill-posed problem (as recently shown). The novel systematic methodology followed herein, demonstrated for Newtonian fluids, involves specially designed experiments, allowing first the independent reliable determination of fluid-mechanical parameters. In this paper, the method is further developed, to determine the complete mass transfer module-characteristics; i.e., the mass transfer problem is modelled/solved, employing the already fully-described flow field. Furthermore, the model is validated using new/detailed experimental data on concentration profiles of a typical solute (urea) in counter-current flow. A single intrinsic-parameter value (i.e., the unknown effective solute-diffusivity in the membrane) satisfactorily fits all data. Significant insights are also obtained regarding the relative contributions of convective and diffusive mass-transfer. This study completes the method for reliable module simulation in Newtonian-liquid flow and provides the basis for extension to plasma/blood haemofiltration, where account should be also taken of oncotic-pressure and membrane-fouling effects.

Poly(Lactic Acid) Block Copolymers with Poly(Hexylene Succinate) as Microparticles for Long-Acting Injectables of Risperidone Drug.

In the present work, Risperidone microparticles from poly(lactic acid)/poly(hexylene succinate) (PLA-b-PHSu) block copolymers in different ratios, 95/05, 90/10 and 80/20 w/w, were examined as long-acting injectable formulations. Nuclear magnetic resonance (NMR) was used to verify the successful synthesis of copolymers. Enzymatic hydrolysis showed an increase in weight loss as the content of PHSu increased, while the cytotoxicity studies confirmed the biocompatibility of the copolymers. The polyesters were further used to encapsulate Risperidone by spray drying. The drug-loaded microparticles were studied by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and X-ray diffraction (XRD). SEM microphotographs confirmed that spherically shaped microparticles were prepared with sizes about 5-12 µm, while XRD and differential scanning calorimetry (DSC) studies evidenced that Risperidone was encapsulated in amorphous form. The drug loading and the entrapment efficiency of Risperidone were studied as well as the in vitro release from the prepared microparticles. As the content of PHSu increased, a higher release of Risperidone was observed, with PLA-b-PHSu 80/20 w/w succeeding to release 100% of RIS within 12 days. According to theoretical modeling, the kinetics of RIS release from PLA-b-PHSu microparticles is complex, governed by both diffusion and polymer erosion.

Wetting properties of dehydrated biofilms under different growth conditions.

Biofilms are resilient to environmental conditions and often resistant even to strong disinfectants. It is crucial to investigate their interfacial properties, which can be effectively characterized by wetting analysis. Wetting phenomena on biofilm surfaces have been poorly investigated in literature, in particular a systematic study of wetting on real biofilm-coated substrates including the application of external body forces (forced wetting, i.e.: centrifugal and gravitational forces) is missing. The aim of this work is to study the role of nutrient and shear flow conditions on wetting properties of Pseudomonas fluorescens dehydrated biofilms, grown on glass substrates. An innovative device (Kerberos®), capable to study spreading/sliding behavior under the application of external body forces, is used here for a systematic analysis of wetting/de-wetting liquid droplets on horizontal substrates under the action of tangential forces. Results prove that, under different growth conditions, (i.e., nutrients and imposed flow), biofilms exhibit different wetting properties. At lower nutrient/shear flow conditions, biofilms show spreading/sliding behavior close to that of pure glass. At higher nutrient and shear flow conditions, droplets on biofilms show spreading followed by imbibition soon after deposition, which leads to peculiar droplet depinning during the rotation test. Wetting properties are derived as a function of the rotation speed from both top and side views videoframes through a dedicated image analysis technique. A detailed analysis of biofilm formation and morphology/topography is also provided here.

SARS-CoV-2 adsorption on suspended solids along a sewerage network: mathematical model formulation, sensitivity analysis, and parametric study.

Accounting for SARS-CoV-2 adsorption on solids suspended in wastewater is a necessary step towards the reliable estimation of virus shedding rate in a sewerage system, based on measurements performed at a terminal collection station, i.e., at the entrance of a wastewater treatment plant. This concept is extended herein to include several measurement stations across a city to enable the estimation of spatial distribution of virus shedding rate. This study presents a pioneer general model describing the most relevant physicochemical phenomena with a special effort to reduce the complicated algebra. This is performed both in the topology regime, introducing a discrete-continuous approach, and in the domain of independent variables, introducing a monodisperse moment method to reduce the dimensionality of the resulting population balance equations. The resulting simplified model consists of a large system of ordinary differential equations. A sensitivity analysis is performed with respect to some key parameters for a single pipe topology. Specific numerical techniques are employed for the integration of the model. Finally, a parametric case study for an indicative-yet realistic-sewerage piping system is performed to show how the model is applied to SARS-CoV-2 adsorption on wastewater solids in the presence of other competing species. This is the first model of this kind appearing in scientific literature and a first step towards setting up an inverse problem to assess the spatial distribution of virus shedding rate based on its concentration in wastewater.

Investigation of Molecular Weight, Polymer Concentration and Process Parameters Factors on the Sustained Release of the Anti-Multiple-Sclerosis Agent Teriflunomide from Poly(ε-caprolactone) Electrospun Nanofibrous Matrices.

In the current work, a series of PCL polyesters with different molecular weights was synthesized and used for the fabrication of nanofibrous patches via electrospinning, as sustained release matrices for leflunomide's active metabolite, teriflunomide (TFL). The electrospinning conditions for each sample were optimized and it was found that only one material with high Mn (71,000) was able to produce structures with distinct fibers devoid of the presence of beads. The successful preparation of the fibers was determined by scanning electron microscopy (SEM).TFL (10, 20 and 30 wt%) in three different concentrations was incorporated into the prepared nanofibers, which were used in in vitro drug release experiments. The drug-loaded nanofibrous formulations were further characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and powder X-ray diffractometry (XRD).It was found that TFL was incorporated in an amorphous form inside the polymeric nanofibers and that significant molecular interactions were formed between the drug and the polyester. Additionally, in vitro dissolution studies showed that the PCL/TFL-loaded nanofibers exhibit a biphasic release profile, having an initial burst release phase, followed by a sustained release until 250 h. Finally, a kinetic analysis of the obtained profiles revealed that the drug release was directly dependent on the amount TFL incorporated into the nanofibers.

SARS-CoV-2 wastewater monitoring using a novel PCR-based method rapidly captured the Delta-to-Omicron ΒΑ.1 transition patterns in the absence of conventional surveillance evidence.

Conventional SARS-CoV-2 surveillance based on genotyping of clinical samples is characterized by challenges related to the available sequencing capacity, population sampling methodologies, and is time, labor, and resource-demanding. Wastewater-based variant surveillance constitutes a valuable supplementary practice, since it does not require extensive sampling, and provides information on virus prevalence in a timely and cost-effective manner. Consequently, we developed a sensitive real-time RT-PCR-based approach that exclusively amplifies and quantifies SARS-CoV-2 genomic regions carrying the S:Δ69/70 deletion, indicative of the Omicron BA.1 variant, in wastewater. The method was incorporated in the analysis of composite daily samples taken from the main Wastewater Treatment Plant of Thessaloniki, Greece, from 1 December 2021. The applicability of the methodology is dependent on the epidemiological situation. During Omicron BA.1 global emergence, Thessaloniki was experiencing a massive epidemic wave attributed solely to the Delta variant, according to genomic surveillance data. Since Delta does not possess the S:Δ69/70, the emergence of Omicron BA.1 could be monitored via the described methodology. Omicron BA.1 was detected in sewage samples on 19 December 2021 and a rapid increase of its viral load was observed in the following 10-day period, with an estimated early doubling time of 1.86 days. The proportion of the total SARS-CoV-2 load attributed to BA.1 reached 91.09 % on 7 January, revealing a fast Delta-to-Omicron transition pattern. The detection of Omicron BA.1 subclade in wastewater preceded the outburst of reported (presumable) Omicron cases in the city by approximately 7 days. The proposed wastewater surveillance approach based on selective PCR amplification of a genomic region carrying a deletion signature enabled rapid, real-time data acquisition on Omicron BA.1 prevalence and dynamics during the slow remission of the Delta wave. Timely provision of these results to State authorities readily influences the decision-making process for targeted public health interventions, including control measures, awareness, and preparedness.

The COVID-19 pandemic as inspiration to reconsider epidemic models: A novel approach to spatially homogeneous epidemic spread modeling.

Epidemic spread models are useful tools to study the spread and the effectiveness of the interventions at a population level, to an epidemic. The workhorse of spatially homogeneous class models is the SIR-type ones comprising ordinary differential equations for the unknown state variables. The transition between different states is expressed through rate functions. Inspired by -but not restricted to- features of the COVID-19 pandemic, a new framework for modeling a disease spread is proposed. The main concept refers to the assignment of properties to each individual person as regards his response to the disease. A multidimensional distribution of these properties represents the whole population. The temporal evolution of this distribution is the only dependent variable of the problem. All other variables can be extracted by post-processing of this distribution. It is noteworthy that the new concept allows an improved consideration of vaccination modeling because it recognizes vaccination as a modifier of individuals response to the disease and not as a means for individuals to totally defeat the disease. At the heart of the new approach is an infection age model engaging a sharp cut-off. This model is analyzed in detail, and it is shown to admit self-similar solutions. A hierarchy of models based on the new approach, from a generalized one to a specific one with three dominant properties, is derived. The latter is implemented as an example and indicative results are presented and discussed. It appears that the new framework is general and versatile enough to simulate disease spread processes and to predict the evolution of several variables of the population during this spread.

Detecting SARS-CoV-2 lineages and mutational load in municipal wastewater and a use-case in the metropolitan area of Thessaloniki, Greece.

The COVID-19 pandemic represents an unprecedented global crisis necessitating novel approaches for, amongst others, early detection of emerging variants relating to the evolution and spread of the virus. Recently, the detection of SARS-CoV-2 RNA in wastewater has emerged as a useful tool to monitor the prevalence of the virus in the community. Here, we propose a novel methodology, called lineagespot, for the monitoring of mutations and the detection of SARS-CoV-2 lineages in wastewater samples using next-generation sequencing (NGS). Our proposed method was tested and evaluated using NGS data produced by the sequencing of 14 wastewater samples from the municipality of Thessaloniki, Greece, covering a 6-month period. The results showed the presence of SARS-CoV-2 variants in wastewater data. lineagespot was able to record the evolution and rapid domination of the Alpha variant (B.1.1.7) in the community, and allowed the correlation between the mutations evident through our approach and the mutations observed in patients from the same area and time periods. lineagespot is an open-source tool, implemented in R, and is freely available on GitHub and registered on bio.tools.

Poly(l-Lactic Acid)-co-poly(Butylene Adipate) New Block Copolymers for the Preparation of Drug-Loaded Long Acting Injectable Microparticles.

The present study evaluates the use of newly synthesized poly(l-lactic acid)-co-poly(butylene adipate) (PLA/PBAd) block copolymers as microcarriers for the preparation of aripiprazole (ARI)-loaded long acting injectable (LAI) formulations. The effect of various PLA to PBAd ratios (95/5, 90/10, 75/25 and 50/50 w/w) on the enzymatic hydrolysis of the copolymers showed increasing erosion rates by increasing the PBAd content, while cytotoxicity studies revealed non-toxicity for all prepared biomaterials. SEM images showed the formation of well-shaped, spherical MPs with a smooth exterior surface and no particle's agglomeration, while DSC and pXRD data revealed that the presence of PBAd in the copolymers favors the amorphization of ARI. FTIR spectroscopy showed the formation of new ester bonds between the PLA and PBAd parts, while analysis of the MP formulations showed no molecular drug-polyester matrix interactions. In vitro dissolution studies suggested a highly tunable biphasic extended release, for up to 30 days, indicating the potential of the synthesized copolymers to act as promising LAI formulations, which will maintain a continuous therapeutic level for an extended time period. Lastly, several empirical and mechanistic models were also tested, with respect to their ability to fit the experimental release data.