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Microfluidic separators play a pivotal role in the biomedical and chemical industries by enabling precise fluid manipulations. Traditional fabrication of these devices typically requires costly cleanroom facilities, which limits their broader application. This study introduces a novel microfluidic device that leverages the passive Zweifach-Fung principle to overcome these financial barriers. Through Lagrangian computational simulations, we optimized an eleven-channel Zweifach-Fung configuration that achieved a perfect 100% recall rate for particles following a specified normal distribution. Experimental evaluations determined 2 mL/h as the optimal total flow rate (TFR), under which the device showcased exceptional performance enhancements in precision and recall for micrometer-sized particles, achieving an overall accuracy of 94% ± 3%. Fabricated using a cost-effective, non-cleanroom method, this approach represents a significant shift from conventional practices, dramatically reducing production costs while maintaining high operational efficacy. The cost of each chip is less than USD 0.90 cents and the manufacturing process takes only 15 min. The development of this device not only makes microfluidic technology more accessible but also sets a new standard for future advancements in the field.

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Although microparticles are frequently used in chemistry and biology, their effectiveness largely depends on the homogeneity of their particle size distribution. Microfluidic devices to separate and purify particles based on their size have been developed, but many require expensive cleanroom manufacturing processes. A cost-effective, passive microfluidic separator is presented, capable of efficiently sorting and purifying particles spanning the size range of 15 µm to 40 µm. Fabricated from Polymethyl Methacrylate (PMMA) substrates using laser ablation, this device circumvents the need for cleanroom facilities. Prior to fabrication, rigorous optimization of the device's design was carried out through computational simulations conducted in COMSOL Multiphysics. To gauge its performance, chitosan microparticles were employed as a test case. The results were notably promising, achieving a precision of 96.14 %. This quantitative metric underscores the device's precision and effectiveness in size-based particle separation. This low-cost and accessible microfluidic separator offers a pragmatic solution for laboratories and researchers seeking precise control over particle sizes, without the constraints of expensive manufacturing environments. This innovation not only mitigates the limitations tied to traditional cleanroom-based fabrication but also widens the horizons for various applications within the realms of chemistry and biology.

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Microplastics (MPs) are widespread pollutants of emerging concern, and the risks associated with their ingestion have been reported in many organisms. Terrestrial environments can be contaminated with MPs, and terrestrial organisms, including arthropods, are predisposed to the risk of ingesting MPs. In the current study, the larvae of the paper wasp Polistes satan were fed two different doses (6 mg or 16 mg at once) of polystyrene MPs (1.43 mm maximum length), and the effects of these treatments on immature development and survival till adult emergence were studied. Ingestion of the two doses resulted in mortality due to impaired defecation prior to pupation. The survival of larvae that ingested 16 mg of MPs was significantly lower than that of the control. The ingestion of 16 mg of MPs also reduced the adult emergence (11.4%) in comparison to the control (44.4%). MPs were not transferred from the larvae to the adults that survived. These findings demonstrate that MP ingestion can be detrimental to P. satan, e.g. larval mortality can decrease colony productivity and thus the worker force, and that MPs can potentially affect natural enemies that occur in crops, such as predatory social wasps.

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Effective cytokine treatments often require high- and multiple-dose due to the short half-life of these molecules. Here, porcine interferon-alpha (IFNα) is encapsulated in PLGA-chitosan microparticles (IFNα-MPs) to accomplish both slow drug release and drug protection from degradation. A procedure that combines emulsion and spray-drying techniques yielded almost spherical microspheres with an average diameter of 3.00 ± 1.50 µm. SEM, Microtrac, and Z-potential analyses of three IFNα-MP batches showed similar results, indicating the process is reproducible. These studies supported molecular evidence obtained in FTIR analysis, which indicated a compact structure of IFNα-MPs. Consistently, IFNα release kinetics assessed in vitro followed a zero-order behavior typical of sustained release from a polymeric matrix. This study showed that IFNα-MPs released bioactive molecules for at least 15 days, achieving IFNα protection. In addition, pigs treated with IFNα-MPs exhibited overexpression of IFNα-stimulated genes 16 days after treatment. Instead, the expression levels of these genes decreased after day 4th in pigs treated with non-encapsulated IFNα. In vitro and in vivo experiments demonstrated that the formulation improved the prophylactic and therapeutic potential of IFNα, accomplishing molecule protection and long-term release for at least two weeks. The procedure used to obtain IFNα-MPs is reproducible, scalable, and suitable for encapsulating other drugs.

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Microencapsulation of microorganisms has been studied to increase product shelf life and stability to enable the application in sustainable agriculture. In this study, the microencapsulation of Trichoderma asperellum conidia by spray drying (SD) was evaluated. The objective was to assess the effect of drying air temperature and wall material (maltodextrin DE20, MD20) concentration on the microencapsulation and to identify the optimum conditions to produce, in high yield, microparticles with low moisture, high conidial viability and conidial survival. Microparticles were characterized in terms of morphology, particle size, and shelf life. A central composite rotatable design (CCRD) was used to evaluate the effect of operating parameters on drying yield (DY), moisture content, conidial viability (CV), and conidial survival (SP). Microencapsulation experiments were carried out under optimum conditions to validate the obtained model. The optimum temperature and MD20/conidia dry weight ratios were 80 °C and 1:4.5, respectively, which afforded a drying yield of 63.85 ± 0.86%, moisture content of 4.92 ± 0.07%, conidial viability of 87.10 ± 1.16%, and conidial survival of 85.78 ± 2.88%. Microencapsulation by spray drying using MD20 as wall material extended the viability of conidia stored at 29 °C compared with the control. The mathematical models accurately predicted all the variables studied, and the association of the microencapsulation technique using DE20 maltodextrin was able to optimize the process and increase the product's shelf life. It was also concluded that high inlet air temperatures negatively affected conidia survival, especially above 100 °C.

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Oral sildenafil (SDF) is used to treat pulmonary arterial hypertension (PAH), and its bioavailability is approximately 40%. Several formulations of nano and microparticles (for pulmonary delivery) are being developed because it is possible to improve characteristics such as release time, bioavailability, dose, frequency, and even directly target the drug to the lungs. This review summarizes the latest SDF drug delivery systems for PAH and explains challenges related to the development, the preclinical, and the clinical studies. A scoping review was conducted by searching electronic databases including PubMed, Scopus, and Web of Science to identify studies published between 2001 and 2021. From 300 articles found, 31 met the inclusion criteria. This review identified colloidal formulations such as polymeric, lipid, and metal-organic framework nanoparticles. Strategies were determined to reach the deep airways such as polymeric microparticles, large porous microparticles, nanocomposites, and nano in microparticles. Finally, aspects related to toxicological, pharmacokinetics, and gaps in information for potential use in humans were discussed. SDF formulations are significant candidates for the treatment of PAH by inhalation. In summation, future preclinical studies are still required in large animals, as there is no particular formulation yet submitted to clinical studies.

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The fluidic barrier in centrifugal microfluidic platforms is a newly introduced concept for making multiple emulsions and microparticles. In this study, we focused on particle generation application to better characterize this method. Because the phenomenon is too fast to be captured experimentally, we employ theoretical models to show how liquid polymeric droplets pass a fluidic barrier before crosslinking. We explain how secondary flows evolve and mix the fluids within the droplets. From an experimental point of view, the effect of different parameters, such as the barrier length, source channel width, and rotational speed, on the particles' size and aspect ratio are investigated. It is demonstrated that the barrier length does not affect the particle's ultimate velocity. Unlike conventional air gaps, the barrier length does not significantly affect the aspect ratio of the produced microparticles. Eventually, we broaden this concept to two source fluids and study the importance of source channel geometry, barrier length, and rotational speed in generating two-fluid droplets.

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INTRODUCTION: Biopredictive release tests are commonly used in the evaluation of oral medicines. They support decision-making in formulation development and allow predictions of the expected in-vivo performances. So far, there is limited experience in the application of these methodologies to injectable drug products. AREAS COVERED: Parenteral drug products cover a variety of dosage forms and administration sites, including subcutaneous, intramuscular, and intravenous injections. In this area, developing biopredictive and biorelevant methodologies often confronts us with unique challenges and knowledge gaps. Here, we provide a formulation-centric approach and explain the key considerations and workflow when designing biopredictive assays. Also, we outline the key role of computational methods in achieving clinical relevance and put all considerations into context using liposomal nanomedicines as an example. EXPERT OPINION: Biopredictive tools are the need of the hour to exploit the tremendous opportunities of injectable drug products. A growing number of biopharmaceuticals such as peptides, proteins, and nucleic acids require different strategies and a better understanding of the influences on drug absorption. Here, our design strategy must maintain the balance between robustness and complexity required for effective formulation development.

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Although polyphenols have great pharmacological potential, the main disadvantage is that they have low bioavailability at the desired site. Thus, the use of biocompatible systems for drug delivery is a strategy that is currently gaining great interest. The objective of this study is to evaluate the effect of microencapsulation of caffeic acid and pinocembrin on the antioxidant and antiangiogenic activity of both polyphenols, by the use of nPSi-ßCD composite microparticles. For this HUVEC, cells were exposed to H2O2 and to treatments with polyphenols in solution and loaded in the composite microparticle. The polyphenols were incorporated into a microparticle using nanoporous silicon, chitosan and a ß-cyclodextrin polymer as the biomaterial. The evaluation of the antiangiogenic effect of the treatments with polyphenols in solution and microencapsulated was carried out through functional tests, and the changes in the expression of target genes associated with the antioxidant pathway and angiogenesis was performed through qPCR. The results obtained show that the caffeic acid and pinocembrin have an antioxidant and antiangiogenic activity, both in solution as microencapsulated. In the caffeic acid, a greater biological effect was observed when it was incorporated into the nPSi-ßCD composite microparticle. Our results suggest that the nPSi-ßCD composite microparticle could be used as an alternative oral drug administration system.

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The present study aims to correlate the sample-to-cutoff ratios (S/CO) distributions of reactive results for HTLV-1/2 antibodies with the detection of proviral DNA in a population of blood donor candidates. It was carried out a retrospective data search of 632 HTLV-1/2 reactive samples, submitted to confirmatory testing from January 2015 to December 2019. Serological screening was performed by chemiluminescent microparticle immunoassay Architect rHTLV-I/II, whereas confirmatory testing was performed by in-house real-time polymerase chain reaction method. 496 out of 632 samples (78%) had undetectable HTLV-1/2 proviral DNA and 136 (22%) had detectable proviral DNA. HTLV infection was not confirmed in any individual for whom the S/CO ratio value was <4, and proviral DNA detection rates gradually escalated as S/CO ratio values increased. The sensitivity and predictive positive value found for the Architect rHTLV-I/II was 100% and 22%, respectively. The receiver operating characteristic (ROC) curve analysis showed that the optimal S/CO ratio value for predicting the presence of HTLV-1/2 was 18.11. High S/CO ratios were more associated with the detection of proviral DNA. The S/CO ratio value <4 suggests excluding true HTLV infection and the risk of blood transmission (AU).

O estudo tem como objetivo correlacionar às distribuições das razões sample-to-cutoff (S/CO) de resultados reagentes para anticorpos HTLV-1/2 com a detecção de DNA proviral em uma população de candidatos à doação de sangue. Realizou-se uma busca retrospectiva de dados de 632 amostras reagentes para HTLV-1/2 submetidas à testagem confirmatória entre janeiro de 2015 a dezembro de 2019. A triagem sorológica foi realizada pelo imunoensaio quimioluminescente de micropartículas Architect rHTLV-I/II, enquanto o teste confirmatório foi realizado pelo método de PCR em tempo real in-house. 496 de 632 amostras (78%) apresentaram DNA proviral indetectável e 136 (22%) apresentaram DNA proviral detectável. A infecção por HTLV não foi confirmada em nenhum indivíduo com valor de S/CO <4 e as taxas de detecção de DNA proviral escalonaram gradualmente à medida que as razões S/CO aumentaram. A sensibilidade e valor preditivo positivo encontrados para o Architect rHTLV-I/II foram 100% e 22%, respectivamente. Utilizando análise de curva ROC, o valor de razão S/CO ideal para predizer a presença de DNA proviral foi de 18,11. Razões S/CO elevadas foram mais associadas à detecção de DNA proviral. Em suma, o valor de S/CO <4 sugere a exclusão de infecção por HTLV e o risco de transmissão pelo sangue (AU).

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