Nano-enabled smart and functional materials toward human well-being and sustainable developments.

Fabrication and operation on increasingly smaller dimensions have been highly integrated with the development of smart and functional materials; they are key to many technological innovations to meet economic and societal needs. Along with many researchers worldwide, the Waterloo Institute for Nanotechnology (WIN) has long realized the synergetic interplays between nanotechnology and functional materials and designated "Smart & Functional Materials" as one of its four major research themes. Thus far, WIN researchers have utilized the properties of smart polymers, nanoparticles, and nanocomposites to develop active materials, membranes, films, adhesives, coatings, and devices with novel and improved properties and capabilities. In this review article, we aim to highlight some of the recent developments on the subject including our own research and key research literature in the context of the UN Sustainability development goals.

Flexible hydrogels connecting adhesion and wetting.

Raindrops falling on window-panes spread upon contact, whereas hail can cause dents or scratches on the same glass window upon contact. While the former phenomenon resembles classical wetting, the latter is dictated by contact and adhesion theories. The classical Young-Dupre law applies to the wetting of pure liquids on rigid solids, whereas conventional contact mechanics theories account for rigid-on-soft or soft-on-rigid contacts with small deformations in the elastic limit. However, the crossover between adhesion and wetting is yet to be fully resolved. The key lies in the study of soft-on-soft interactions with material properties intermediate between liquids and solids. In this work, we translate adhesion to wetting by experimentally probing the static signature of hydrogels in contact with soft PDMS of varying elasticity of both the components. Consequently, we probe this transition across six orders of magnitude in terms of the characteristic elasto-adhesive parameter of the system. In doing so, we reveal previously unknown phenomenology and a theoretical model which smoothly bridges adhesion of glass spheres with total wetting of pure liquids on any given substrate.

Density Functional Theory Approach to Interpret Elastowetting of Hydrogels.

Sessile hydrogel drops on rigid surfaces exhibit a wetting/contact morphology intermediate between liquid drops and glass spheres. Using density functional theory, we reveal the contact forces acting between a hydrogel and a rigid glass surface. We show that while transitioning from liquid-like to solid-like hydrogels, there exists a critical hydrogel elasticity that enables a switch from attractive-to-repulsive interaction with the underlying rigid glass surface. Our theoretical model is validated by experimental observations of sessile polyacrylamide hydrogels of varying elasticity on glass surfaces. Further, the proposed model successfully approaches Young's law in the pure liquid limit and work of adhesion in the glassy limit. Lastly, we show a modified contact angle relation, taking into account the hydrogel elasticity to explain the features of a distinct hydrogel foot.

Trimethylamine-N-oxide (TMAO) and predicted risk of cardiovascular events after partial nephrectomy.

INTRODUCTION: Emerging evidence suggests that uremic toxins, in particular trimethylamine-N-oxide(TMAO), indoxyl-sulfate(IS), and p-cresyl-sulfate(PCS), may associate with increased risk of cardiovascular events(CVe). However, whether uremic toxins increase after partial nephrectomy(PN) and their correlation with risk for CVe remains unknown. METHODS: 100 patients managed with PN were retrospectively reviewed. TMAO/IS/PCS levels were examined by liquid chromatography-mass-spectrometry. Renal-parenchymal-volume-preservation(RPVP) was estimated from CT scans. Predicted risks for CVe were obtained using the Framingham score. Linear regression assessed association between uremic toxins, GFR and risk of CVe. Logistic regression evaluated factors associated with post-PN TMAO. RESULTS: TMAO, IS and PCS increased from 1.7, 3.7 and 3.5 µmol/L before PN to 3.6, 5.4 and 7.4 µmol/L at latest follow-up, respectively, while GFR declined from 102 to 93 ml/min/1.73 m2 (all p<0.001). TMAO, IS and PCS levels all negatively correlated with GFR(all p<0.001). Predicted 10-year risk of CVe increased from 1.1% pre-PN to 1.7% post-PN(p<0.001), primarily due to increased age(p<0.001), blood pressure(p = 0.002) and total cholesterol(p = 0.003). TMAO(ß = 0.038) and GFR (ß = -0.02) were independent predictors for predicted 10-year CVe risk on multivariable-analysis. Increased TMAO was an early and sustained finding maintained through 5 years, unlike IS, PCS and eGFR. On multivariable analysis, increased pre-PN TMAO(OR = 2.79) and decreased RPVP(OR = 3.23) were identified as independent risk factors for higher post-PN TMAO, while ischemia type/duration failed to correlate. CONCLUSION: Uremic toxin levels increased after PN correlating with reduced GFR. Higher TMAO independently associated with greater predicted 10-year CVe risk. Parenchymal mass preserved rather than ischemia time or type associated with increased TMAO.

The effect of miR-223-3p on endothelial cells in coronary artery disease.

Endothelial cell damage and dysfunction are crucial factors in the development and early stages of coronary artery disease (CAD) and apoptosis plays a significant role in this process. In this study, We aimed to simulate the CAD vascular microenvironment by treating endothelial cells with tumor necrosis factor alpha (TNF-α) to construct an endothelial cell apoptosis model. Our findings revealed that the TNF-α model resulted in increased micro-RNA 223-3p (miR-223-3p) mRNA and Bax protein expression, decreased kruppel-like factor 15 (KLF15) and Bcl-2 protein expression, and decreased cell viability. More importantly, in the TNF-α-induced endothelial cell apoptosis model, transfection with the miR-223-3p inhibitor reversed the effects of TNF-α on Bcl-2, Bax expression. We transfected miRNA-223-3p mimics or inhibitors into endothelial cells and assessed miR-223-3p levels using RT-PCR. Cell viability was detected using CCK8. Western blot technology was used to detect the expression of Bcl-2, Bax, and KLF15. In summary, this study demonstrates the role and possible mechanism of miR-223-3p in endothelial cells during CAD, suggesting that miR-223-3p may serve as a promising therapeutic target in CAD by regulating KLF15.

The volume regulated anion channel VRAC regulates NLRP3 inflammasome by modulating itaconate efflux and mitochondria function.

The NLRP3 inflammasome is a supramolecular complex that is linked to sterile and pathogen-dependent inflammation, and its excessive activation underlies many diseases. Ion flux disturbance and cell volume regulation are both reported to mediate NLRP3 inflammasome activation, but the underlying orchestrating signaling remains not fully elucidated. The volume-regulated anion channel (VRAC), formed by LRRC8 proteins, is an important constituent that controls cell volume by permeating chloride and organic osmolytes in response to cell swelling. We now demonstrate that Lrrc8a, the essential component of VRAC, plays a central and specific role in canonical NLRP3 inflammasome activation. Moreover, VRAC acts downstream of K+ efflux for NLRP3 stimuli that require K+ efflux. Mechanically, our data demonstrate that VRAC modulates itaconate efflux and damaged mitochondria production for NLRP3 inflammasome activation. Further in vivo experiments show mice with Lrrc8a deficiency in myeloid cells were protected from lipopolysaccharides (LPS)-induced endotoxic shock. Taken together, this work identifies VRAC as a key regulator of NLRP3 inflammasome and innate immunity by regulating mitochondrial adaption for macrophage activation and highlights VRAC as a prospective drug target for the treatment of NLRP3 inflammasome and itaconate related diseases.

Molecularly Imprinted Electrochemical Sensors Based on Ti3C2Tx-MXene and Graphene Composite Modifications for Ultrasensitive Cortisol Detection.

The increasing pressure and unhealthy lifestyle are gradually eroding the physical and mental health of modern people. As a key hormone responsible for maintaining the normal functioning of human systems, cortisol plays a vital role in regulating physiological activities. Moreover, cortisol can serve as a marker for monitoring psychological stress. The development of cortisol detection sensors carries immense potential, as they not only facilitate timely adjustments and treatments by detecting abnormal physiological indicators but also provide comprehensive data for conducting research on the correlation between cortisol and several potential diseases. Here, we report a molecularly imprinted polymer (MIP) electrochemical biosensor that utilizes a porous composite (MXG) modified electrode. MXG composite is prepared by combining Ti3C2Tx-MXene sheets and graphene (Gr). MXG composite material with high conductive properties and large electroactive surface area promotes the charge transfer capability of the electrode surface, expands the effective surface area of the sensor, and increases the content of cortisol-imprinted cavities on the electrode, thereby improving the sensing ability of the sensor. By optimizing the preparation process, the prepared sensor has an ultralow lower limit of detection of 0.4 fM, a wide detection range of 1 fM-10 µM, and good specificity for steroid hormones and interfering substances with similar cortisol structure. The ability of the sensor to detect cortisol in saliva was also confirmed experimentally. This highly sensitive and selective cortisol sensor is expected to be widely used in the fields of physiological and psychological care.

Organohydrogels with cellulose nanofibers enhanced supramolecular interactions toward high performance self-adhesive sensing pads.

Gel materials with tailored functions and tissue-like properties have gained significant interest in emerging applications, including tissue engineering scaffolds, flexible electronics, and soft robotics. In this work, we developed a stretchable, flexible, adhesive, and conductive organohydrogel through physical cross-linking of the poly (N-[tris (hydroxymethyl) methyl] acrylamide-co-acrylamide) (denoted as P(THMA-AM)) network in the presence of cellulose nanofiber (CNF), sodium chloride, and glycerol. The gel matrix is rich in intermolecular interactions, including hydrogen bonding and ionic interactions, which contribute to a highly compact and cohesive structure without the requirement of any chemical crosslinkers. Moreover, the plasticizing effect of glycerol can mitigate the self-entanglement of CNFs, enhancing their mobility and ultimately conferring the organohydrogel with exceptional stretchability and flexibility. The resulting organohydrogel exhibited superior mechanical properties, self-adhesion, and ionic conductivity, making it an excellent candidate for strain-sensing applications, particularly in distinguishing and monitoring human movements.

Modelo de atención farmacéutica en medicina de precision en China / Pharmaceutical care model in precision medicine in China

Pharmacy service is to provide individualized pharmaceutical care for patients, which should follow the current evidence-based pharmacy, and constantly verify the evidence and then produce new evidence. In pharmaceutical care, differences are often found in the efficacy and adverse reactions of drugs among individuals, even within individuals, which are closely related to patient's genetics, liver and kidney functions, disease states, and drug interactions. Back in the 1980s, therapeutic drug monitoring (TDM) has been applied to routinely monitor the blood drug concentration of patients taking antiepileptic drugs or immunosuppressants after transplantation to provide individualized dosage recommendations and accumulate a large amount of pharmacokinetic (PK)/pharmacodynamic (PD) data. As individualized pharmaceutical care proceeds, the concept of precision medicine was introduced into pharmacy services in combination with evidence-based pharmacy, PK/PD theories and big data to further promote the TDM technology and drugs, and carry out pharmacogenomics analysis. The TDM and pharmacogenomics have been applied gradually to the fields of antimicrobial, antitumor and antipsychotic drugs and immunosuppressants. Based on the concept of precision pharmacy, we adpoted approaches including PK/PD, quantitative pharmacology, population pharmacokinetics, and big data machine learning to provide more personalized pharmacy services, which is mainly for special patients, such as critical patients, patients with interaction risk of multiple drugs, patients with liver and renal insufficiency, pregnant women, children and elderly patients. As the service pattern of precision pharmacy has been constructed and constantly improved, better evidence in clinical practice will be produced to provide patients with better precision pharmacy service. (AU)

El servicio de farmacia se encarga de prestar atención farmacéutica personalizada a los pacientes. Los servicios de farmacia deben utilizar aquellas prácticas con mayor nivel de evidencia, y realizar una continua validación de dicha evidencia antes de elaborar nuevas prácticas. En la terapia farmacológica, se observan diferencias inter e intra individuales respecto a los efectos terapéuticos y a las reacciones adversas de los medicamentos, lo que está estrechamente relacionado con las variaciones genéticas, la función hepática y renal, el estado de la enfermedad y la interacción entre medicamentos. Desde la década de los 80 del siglo pasado, se utiliza la monitorización terapéutica de fármacos (MTF) de forma rutinaria para controlar las concentraciones sanguíneas de fármacos antiepilépticos o de inmunosupresores postrasplante y elaborar recomendaciones de dosis personalizadas y recoger una gran cantidad de datos farmacocinéticos (PC)/farmacodinámicos (PD). Con el desarrollo de la atención farmacéutica personalizada, el concepto de medicina de precisión se introduce en la atención farmacéutica, combinando la farmacia basada en evidencias, los enfoques PC/PD y los macrodatos (big data), promover técnicas de MTF en medicamentos, y la realización de análisis farmacogenómicos. La MTF y la farmacogenómica se están aplicando de forma gradual en el tratamiento con antimicrobianos, antitumorales, antipsicóticos e inmunosupresores. Sobre la base del concepto de farmacia de precisión, utilizamos métodos de PC/PD, farmacología cuantitativa, farmacocinética poblacional y aprendizaje automático con big data para ofrecer una atención farmacéutica más personalizada, principalmente a pacientes con necesidades especiales, como los pacientes en estado crítico, con riesgo de interacciones farmacológicas múltiples, pacientes con insuficiencia hepática y renal, mujeres embarazadas, niños y ancianos... (AU)

Pharmaceutical care model in precision medicine in China. / [Artículo traducido] Modelo de atención farmacéutica en medicina de precisión en China.

Pharmacy service is to provide individualized pharmaceutical care for patients, which should follow the current evidence-based pharmacy, and constantly verify the evidence and then produce new evidence. In pharmaceutical care, differences are often found in the efficacy and adverse reactions of drugs among individuals, even within individuals, which are closely related to patients' genetics, liver and kidney functions, disease states, and drug interactions. Back in the 1980s, therapeutic drug monitoring (TDM) has been applied to routinely monitor the blood drug concentration of patients taking antiepileptic drugs or immunosuppressants after transplantation to provide individualized dosage recommendations and accumulate a large amount of pharmacokinetic (PK)/pharmacodynamic (PD) data. As individualized pharmaceutical care proceeds, the concept of precision medicine was introduced into pharmacy services in combination with evidence-based pharmacy, PK/PD theories, and big data to further promote the TDM technology and drugs, and carry out pharmacogenomics analysis. The TDM and pharmacogenomics have been applied gradually to the fields of antimicrobial, antitumor, and antipsychotic drugs and immunosuppressants. Based on the concept of precision pharmacy, we adopted approaches including PK/PD, quantitative pharmacology, population pharmacokinetics, and big data machine learning to provide more personalized pharmacy services, which is mainly for special patients, such as critical patients, patients with interaction risk of multiple drugs, patients with liver and renal insufficiency, pregnant women, children, and elderly patients. As the service pattern of precision pharmacy has been constructed and constantly improved, better evidence in clinical practice will be produced to provide patients with better precision pharmacy service.

Interfacial Compatibility of Core-Shell Cellulose Nanocrystals for Improving Dynamic Covalent Adaptable Networks' Fracture Resistance in Nanohybrid Vitrimer Composites.

The development of polymeric nanocomposites with dynamic covalent adaptable networks and biobased nanomaterials has been a promising approach toward sustainable advanced materials, enabling reprogramming and recycling capabilities. Herein, a core-shell nanohybrid of functionalized cellulose nanocrystals (CNCs) is explored to provide crucial interfacial compatibility for improving the covalent adaptable networks of epoxy-thiol vitrimers in fracture resistance. The poly(ε-caprolactone) (PCL) shells grafted from CNC surfaces can be cross-linked with the covalent adaptable networks via a hot-pressing transesterification process. According to the additive concentration and annealing temperature, the stress relaxation behavior of nanohybrid vitrimer composites can be effectively regulated by the core-shell PCL-grafted CNC (CNC-PCL) nanohybrids from a dispersed to cross-linked interaction. The addition of 15 wt % of the core-shell CNC-PCLs exhibits the reinforced improvement of nanohybrid vitrimer composites in the average Young's modulus of 2.5×, fracture stress of 5.4×, and fracture strain of 2.0×. The research findings might have profound implications for developing synergistic interfacial compatibility between dynamic vitrimer networks and functional nanoparticles for advanced polymeric nanocomposites.

Pharmaceutical care model in precision medicine in China.

Pharmacy service is to provide individualized pharmaceutical care for patients, which should follow the current evidence-based pharmacy, and constantly verify the evidence and then produce new evidence. In pharmaceutical care, differences are often found in the efficacy and adverse reactions of drugs among individuals, even within individuals, which are closely related to patient's genetics, liver and kidney functions, disease states, and drug interactions. Back in the 1980s, therapeutic drug monitoring (TDM) has been applied to routinely monitor the blood drug concentration of patients taking antiepileptic drugs or immunosuppressants after transplantation to provide individualized dosage recommendations and accumulate a large amount of pharmacokinetic (PK)/pharmacodynamic (PD) data. As individualized pharmaceutical care proceeds, the concept of precision medicine was introduced into pharmacy services in combination with evidence-based pharmacy, PK/PD theories and big data to further promote the TDM technology and drugs, and carry out pharmacogenomics analysis. The TDM and pharmacogenomics have been applied gradually to the fields of antimicrobial, antitumor and antipsychotic drugs and immunosuppressants. Based on the concept of precision pharmacy, we adpoted approaches including PK/PD, quantitative pharmacology, population pharmacokinetics, and big data machine learning to provide more personalized pharmacy services, which is mainly for special patients, such as critical patients, patients with interaction risk of multiple drugs, patients with liver and renal insufficiency, pregnant women, children and elderly patients. As the service pattern of precision pharmacy has been constructed and constantly improved, better evidence in clinical practice will be produced to provide patients with better precision pharmacy service.

Rippling Colloidal Polyelectrolyte Complex for Customized Fingerprints with High Tactile Perception.

Fingerprints possess wide applications in personal identification, tactile perception, access control, and anti-counterfeiting. However, latent fingerprints are usually left on touched surfaces, leading to the leakage of personal information. Furthermore, tactile perception greatly decreases when fingerprints are covered by gloves. Customized fingerprints are developed to solve these issues, but it is a challenge to develop fingerprints with various customized patterns using traditional techniques due to their requiring special templates, materials, or instruments. Inspired by ripples on the lake, blowing air is used to generate surface waves on a colloidal polyelectrolyte complex, leading to vertical stratification and the accumulation of particles near the top of the film layer. As water rapidly evaporates, the viscosity of these particles significantly increases and the wave is solidified, forming fingerprint patterns. These customized fingerprints integrate functions of grasping objects, personal identification without leaving latent fingerprints and tactile perception enhancement, which can be applied in information security, anti-counterfeiting, tactile sensors, and biological engineering.

The Determination of Polymyxin B in Critically Ill Patients by the HPLC-MS/MS Method.

Polymyxin B (PB) is a dose-dependent drug used to treat multidrug-resistantgram-negative bacteria, for which a suitable method is needed to determine clinical samples. A simple, economical, and efficient high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method was developed and validated for polymyxin B1 (PB1), polymyxin B1-Ile (PB1-I), polymyxin B2 (PB2), and polymyxin B3 (PB3) in human plasma. Chromatographic column was Waters BEH C18 column (2.1 × 50 mm, 1.7 µm). Phase A was water with 0.2% formic acid (FA), and phase B was acetonitrile containing 0.2% FA. The elution method is gradient elutio. The total analysis time was 5 min. The pretreatment method involved protein precipitation using acetonitrile containing 0.2% trifluoroacetic acid and 0.1% FA as the precipitant. The recovery rate was 92-99%. The total quantity of PB1 and PB1-I was measured in the linear range of 100-8000 ng/mL. Simultaneously, the total amounts of PB2 and PB3 were measured in the linear range of 11.9-948.5 ng/mL. This validated method was successfully applied to the pharmacokinetics of PB in critically ill patients.

Multi-thermo responsive double network composite hydrogel for 3D printing medical hydrogel mask.

3D printing of multifunctional hydrogels offers great opportunities for developing innovative biomedical technologies as it can provide custom-designed shapes and structures conformal to arbitrary contours. There have been significant improvements of the 3D printing techniques, but the available printable hydrogel materials limit the progress. Here, we investigated the use of a poloxamer diacrylate (Pluronic P123) to augment the thermo-responsive network composed of poly(N-isopropylacrylamide) and develop a multi-thermoresponsive hydrogel for photopolymerization 3D printing. The hydrogel precursor resin was synthesised to be printable with high-fidelity of fine structures and once cured can form a robust thermo-responsive hydrogel. By utilizing N-isopropyl acrylamide monomer and a Pluronic P123 diacrylate crosslinker as 2 separate thermo-responsive components it was found that the final hydrogel displayed 2 distinct lower critical solution temperature (LCST) switches. This enables the loading of hydrophilic drugs at fridge temperature and improving the strength of the hydrogel at room temperature while still maintaining a drug release at body temperature. The thermo-responsive material properties of this multifunctional hydrogel material system were investigated, showing a significant promise as a medical hydrogel mask. Furthermore, it is demonstrated that it can be printed in sizes large enough to fit and adhere to a human face at 1:1 scale with high dimensional accuracy, as well as its ability to load with hydrophilic drugs.

A critical review of microplastic degradation and material flow analysis towards a circular economy.

The resilience and low cost of plastics has made their usage ubiquitous, but is also the cause of their prevalence and longevity as waste. Plastic pollution has become a great concern to the health and wellbeing of ecosystems around the world; microplastics are a particular threat, due to their high mobility, ease of ingestion by wildlife, and ability to adsorb and carry toxic contaminants. Material flow analysis has been widely applied to examine stocks and flows of materials in other industries, and has more recently been applied to plastics to examine areas where waste can reach the environment. However, while much research has gone into the environmental fate of microplastics, degradation strategies have been a lesser focus, and material flow analysis of microplastics has suffered from lack of data. Furthermore, the variety of plastics, their additives, and any contaminants pose a significant challenge in degrading (and not merely fragmenting) microplastic particles. This review discusses the current degradation strategies and solutions for dealing with existing and newly-generated microplastic waste along with examining the status of microplastics-based material flow analysis, which are critical for evaluating the possibility of incorporating microplastic waste into a circular economy. The degradation strategies are critically examined, identifying challenges and current trends, as well as important considerations that are frequently under-reported. An emphasis is placed on identifying missing data or information in both material flow analysis and degradation methods that could prove crucial in improving understanding of microplastic flows, as well as optimizing degradation strategies and minimizing any negative environmental impact.

Capillary pressure mediated long-term dynamics of thin soft films.

HYPOTHESIS: The conventional solid-solid contact is well studied in the literature. However, a number of practical applications, such as adhesive patches and biomimetic surfaces, require a much deeper understanding of soft contact where there is a distinct time-dependent adhesion behavior due to the dual-phase structure (solids and liquids). To understand this, currently existing solid-solid contact behavior is extrapolated to soft contact, wherein the size-effect of the gel film and the preload are typically neglected. When introducing the finite-size effect and preload, gels could experience distinctive long-term contact dynamics in contact with another material. EXPERIMENTS: We reconstruct the evolving surface profile of the gel films intercalated between a glass sphere and glass slide using dual wavelength-reflection interference contrast microscopy. The macro-sized glass sphere compresses the gel. The indentation depth is comparable to the gel film thickness, wherein the conventional contact theories are inapplicable. FINDINGS: The gel surface experiences two deformation stages. The natural preload and elastic force develop the contact area in the early state. In the later state, the viscous free molecules of the gel develop the ridge. We discover that the residual surface stress relaxes over 85 hr. Our findings on the long-term gel deformation provide a new perspective on soft adhesion, from developing soft adhesives to understanding biological tissues.

Antifungal prophylactic effectiveness and intrapulmonary concentrations of voriconazole versus posaconazole in lung transplant recipients.

Invasive fungal diseases (IFDs) are one of the leading causes of death in lung transplant recipients. This study aimed to compare the antifungal prophylactic effectiveness, intrapulmonary and plasma levels of voriconazole with posaconazole in lung transplant recipients. This retrospective cohort study analyzed adult recipients who underwent lung transplantation between June 2017 and December 2020. Voriconazole oral tablets or posaconazole oral suspension was used for prophylaxis against posttransplant IFD. Drug concentrations in bronchoalveolar lavage fluid (BALF) and plasma were measured by using liquid chromatography-mass spectrometry. The 182 recipients included 142 in the voriconazole group and 40 in the posaconazole group. The trough plasma levels were comparable between voriconazole and posaconazole (1.65 ± 0.09 vs. 1.69 ± 0.03 µg/ml, P = 0.55). However, the BALF levels were significantly higher for posaconazole than voriconazole (17.47 ± 11.51 vs. 0.56 ± 0.49 µg/ml, P < 0.001). There was no significant difference in the total incidence of breakthrough IFDs between the voriconazole and posaconazole groups (10.6% vs. 7.5%, P = 0.77). The intrapulmonary concentrations of posaconazole were significantly higher than voriconazole. The two agents had comparable antifungal prophylactic effectiveness.

A Novel Berberine-Glycyrrhizic Acid Complex Formulation Enhanced the Prevention Effect to Doxorubicin-Induced Cardiotoxicity by Pharmacokinetic Modulation of Berberine in Rats.

Developing a new drug delivery system is one of the useful approaches to overcome the limited use of berberine (BBR) to enhance its absorption and bioavailability. We prepared a novel berberine-glycyrrhizic acid (BBR-GL) complex formulation to increase the plasma concentration and bioavailability of BBR by improving BBR solubility and lowering the absorption barrier. The complex formulation with BBR and GL in the ratio 1:1 was developed through the self-assembly process and evaluated in vitro. Compared with BBR and BBR/GL physical mixture, the BBR-GL complex showed different characteristics by SEM, DSC, FT-IR, and PXRD measurement. In pharmacokinetic evaluation, the BBR-GL complex significantly increased the plasma concentration of BBR and the major metabolite berberrubine (BBB), with the AUC of BBR elevated to 4.43-folds, while the complex was safe as BBR. Furthermore, doxorubicin (DOX) was used to induce cardiotoxicity. Hematological study, histopathological examinations, electrocardiography (ECG), cardiac secretion measurement, and biochemical index analysis proved that the model of doxorubicin-induced cardiotoxicity (DIC) was conducted successfully. With the AUC of BBR increasing in the BBR-GL complex and the absorbed complex itself, the BBR-GL complex enhanced prevention effect to DIC and exhibited a significant prevention effect to attenuate heart damage. Our findings demonstrated that a novel BBR-loaded BBR-GL complex formulation could increase BBR plasma concentration. Improvement of BBR bioavailability by the BBR-GL complex could coordinate with GL to attenuate DIC. Concerning the safety of the drug delivery system at present, the BBR-GL complex could be a potential therapeutic formulation for the prevention of cardiac damage in the clinical application of doxorubicin.