Metabolic basis of solute carrier transporters in treatment of type 2 diabetes mellitus

Solute carriers (SLCs) constitute the largest superfamily of membrane transporter proteins. These transporters, present in various SLC families, play a vital role in energy metabolism by facilitating the transport of diverse substances, including glucose, fatty acids, amino acids, nucleotides, and ions. They actively participate in the regulation of glucose metabolism at various steps, such as glucose uptake (e.g., SLC2A4/GLUT4), glucose reabsorption (e.g., SLC5A2/SGLT2), thermogenesis (e.g., SLC25A7/UCP-1), and ATP production (e.g., SLC25A4/ANT1 and SLC25A5/ANT2). The activities of these transporters contribute to the pathogenesis of type 2 diabetes mellitus (T2DM). Notably, SLC5A2 has emerged as a valid drug target for T2DM due to its role in renal glucose reabsorption, leading to groundbreaking advancements in diabetes drug discovery. Alongside SLC5A2, multiple families of SLC transporters involved in the regulation of glucose homeostasis hold potential applications for T2DM therapy. SLCs also impact drug metabolism of diabetic medicines through gene polymorphisms, such as rosiglitazone (SLCO1B1/OATP1B1) and metformin (SLC22A1-3/OCT1-3 and SLC47A1, 2/MATE1, 2). By consolidating insights into the biological activities and clinical relevance of SLC transporters in T2DM, this review offers a comprehensive update on their roles in controlling glucose metabolism as potential drug targets.

Characteristic analysis of fibracel carriers for animal cell culture / 中国生物制品学杂志

@#Objective To investigate the surface properties of different fibracel carriers and their culture effects on different cells.Methods Three fibracel carriers(A,B,C)were selected to analyze the chemical element composition of their materials,and the contact angles of the carriers before and after pretreatment with 0. 1 mol/L NaOH solution were tested. By measuring the adhesion effect and glucose consumption of Vero,MDCK and MRC-5 cells on the carrier,and observing the cell growth state by fluorescent staining,the cell adhesion efficiency and culture effect of the three carriers were compared and analyzed.Results The three carriers were mainly composed of C,H,O,and contained a small amount of N and S elements. Before pretreatment,the contact angle of carrier B was 0°,which was significantly lower than that of A[(109 ± 3. 13)°]and C[(121 ± 6. 82)°]（each F = 709. 1,each P < 0. 000 1）,and the hydrophilicity was stronger. Carriers A and C had poor hydrophilicity. After pretreatment,the contact angles of the surfaces of the three carriers A,B,and C were all 0°,with no significant difference(F = 0. 069 4,P > 0. 05),all of which were hydrophilic. The adherence rates of the three types of carriers within 3 h of cell culture were all above 80%. The cells were dense and evenly grown on the carrier fibers,the glucose consumption curves tended to“S”type,and the continuous cell culture effect was good. The total glucose consumption of carrier A and carrier C was basically the same,and carrier B was lower than carrier A and carrier C.Conclusion The chemical element composition and the relationship between the hydrophilic and hydrophobic properties of the three fibracel carriers were analyzed,and the adhesion rate and culture effect of Vero,MDCK and MRC-5 cells were evaluated,which provide reference for the subsequent research and production application of fibracel carriers.

Impacto del Programa de prevención de anemia por hematíes falciformes

Introducción: la anemia de células falciformes es una enfermedad genética autosómica recesiva considerada la enfermedad hereditaria más frecuente en Cuba. El Programa Cubano de prevención de anemia por hematíes falciformes, se basa en el pesquisaje mediante estudio de electroforesis de hemoglobina a todas las gestantes, el cual es aplicado desde el año 1983. Objetivo: describir el impacto del Programa Cubano de prevención de anemia por hematíes falciformes en Granma, en el período de 1987-2021. Métodos: se realizó un estudio observacional, ambipestivo, de serie de casos en las gestantes pertenecientes a la provincia Granma en el período 1987-2021. Se revisaron las estadísticas de los departamentos municipales y provincial. Se analizaron las variables como frecuencia de portadoras, variantes de hemoglobina, cobertura de esposos estudiados, diagnóstico prenatal molecular y casos positivos. Para el análisis estadístico se emplearon medidas de resumen como frecuencias absolutas y relativas. Resultados: se comprobó que la frecuencia de portadoras de la provincia es de 3,9 %. La variante más frecuente es la Hb AS. Se estudiaron 62 % de los esposos. Se realizó el 70,3 % de los diagnósticos moleculares, de los cuales 21,3 % fue positivo optando por la terminación voluntaria de la gestación en el 69 % de ellos. Conclusiones: se logró impacto del Programa Cubano de prevención de anemia por hematíes falciformes en el período de 1987-2021 en cuanto a la detección de portadoras de la enfermedad, frecuencia de diagnósticos prenatales moleculares, enfermos e interrupciones por esta causa.

Introduction: Sickle cell anemia is an autosomal recessive genetic disease. It is considered the most common hereditary disease in Cuba. The Cuban sickle cell anemia prevention Program is based on the screening of all pregnant women by hemoglobin electrophoresis. This program has been applied since 1983. Objective: To describe the impact of the Cuban sickle cell anemia prevention Program during the period 1987-2021. Methods: An observational study was conducted on a series of cases of pregnant women belonging to the province of Granma in the period from 1987 to 2021. Municipal and provincial statistics were reviewed. Variables such as carrier frequency, hemoglobin variants, coverage of studied spouses, molecular prenatal diagnosis, and positive cases were analyzed. Summary measures such as absolute and relative frequencies were used for statistical analysis. Results: The carrier frequency in the province was found to be 3.9%. The most common variant is Hb AS. Sixty-two percent of spouses were screened. Molecular diagnosis was performed in 70.3%, of which 21.3% were positive and 69% opted for voluntary abortion. Conclusions: The Cuban Sickle Cell Disease Prevention Program has had a great impact on halting the number of carriers of the disease, the frequency of prenatal molecular diagnoses, and the number of patients with sickle cell anemia in the period 1987-2021.

Introdução: A anemia falciforme é uma doença genética autossómica recessiva, sendo considerada a doença hereditária mais comum em Cuba. O programa cubano de prevenção da anemia falciforme baseia-se no rastreio de todas as mulheres grávidas através da eletroforese da hemoglobina, que tem sido aplicado desde 1983. Objetivo: Descrever o impacto do Programa Cubano de Prevenção da Anemia Falciforme durante o período 1987-2021. Métodos: Foi realizado um estudo observacional de uma série de casos de mulheres grávidas pertencentes à província de Granma no período de 1987 a 2021. Foram revistas estatísticas municipais e provinciais. Foram analisadas variáveis como frequência de portadores, variantes de hemoglobina, cobertura de cônjuges estudados, diagnóstico pré-natal molecular e casos positivos. Para a análise estatística foram utilizadas medidas de síntese como frequências absolutas e relativas. Resultados: A frequência de portadores na província foi de 3,9%. A variante mais comum é a Hb AS. Sessenta e dois por cento dos cônjuges foram rastreados. O diagnóstico molecular foi efectuado em 70,3%, dos quais 21,3% foram positivos e 69% optaram pelo aborto voluntário. Conclusões: O Programa Cubano de Prevenção da Doença Falciforme teve um grande impacto na redução do número de portadores da doença, na frequência dos diagnósticos moleculares pré-natais e no número de pacientes com anemia falciforme no período 1987-2021.

Lipid carriers for mRNA delivery

Messenger RNA (mRNA) is the template for protein biosynthesis and is emerging as an essential active molecule to combat various diseases, including viral infection and cancer. Especially, mRNA-based vaccines, as a new type of vaccine, have played a leading role in fighting against the current global pandemic of COVID-19. However, the inherent drawbacks, including large size, negative charge, and instability, hinder its use as a therapeutic agent. Lipid carriers are distinguishable and promising vehicles for mRNA delivery, owning the capacity to encapsulate and deliver negatively charged drugs to the targeted tissues and release cargoes at the desired time. Here, we first summarized the structure and properties of different lipid carriers, such as liposomes, liposome-like nanoparticles, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanoemulsions, exosomes and lipoprotein particles, and their applications in delivering mRNA. Then, the development of lipid-based formulations as vaccine delivery systems was discussed and highlighted. Recent advancements in the mRNA vaccine of COVID-19 were emphasized. Finally, we described our future vision and perspectives in this field.

The Contemporary Value of Carrying forward Norman Bethune Spirit in the Context of Sudden Public Health Crisis / 中国医学伦理学

The spirit of Norman Bethune was formed during the period of the Comprehensive Anti-Japanese War, and played an important role in shaping thought and promoting foreign exchanges in the subsequent inheritance and development process. Promoting the spirit of Norman Bethune in the context of sudden public health crisis, relying on its spiritual strength and extensive influence, and in line with China’s anti-epidemic experience, explaining its principles, methods, organizations, driving forces, and exemplary experiences, so that the Norman Bethune spirit can be promoted and developed in the context of sudden public health crisis, giving its a strong contemporary appeal.

Research progress of platelets and their derivatives based drug delivery systems / 中国输血杂志

Platelets play an important role in physiological and pathological activities such as thrombosis, inflammation and tumorigenesis. At present, the application of platelets in drug delivery systems is increasingly studied. Compared with traditional drug delivery systems, new drug delivery systems based on platelets and their derivatives can effectively improve the circulation time and selective accumulation, and reduce the occurrence of related immune reactions or off-target toxic and side effects. In this paper, the types and applications of platelet and its derivatives drug delivery systems were summarized in order to provide reference for platelet-related drug delivery research.

Micro/nano hierarchical structure of titanium surface promotes MC3T3-E1 adhesion proliferation and drug loading potential evaluation / 口腔疾病防治

Objective @# To investigate the effect of micro/nano hierarchical structures on the adhesion and proliferation of MC3T3-E1 cells, evaluate the drug delivery potential of titanium surfaces, and provide a reference for the modification of selected areas of titanium surfaces to enhance drug delivery and slow drug release. @*Methods @# Pure titanium samples (10 mm in diameter and 2.5 mm in thickness) were randomly divided into a polished group (T), anodized group (TO), and micro/nano hierarchical structure group (FTO) according to the surface treatment of the titanium. The T group was polished, the TO group was treated with anodic oxidation technology, and the FTO group was treated by femtosecond laser etching combined with anodic oxidation technology. The three surface morphologies were observed by scanning electron microscopy (SEM), the wettability of the surface was measured by the contact angle, and the surface chemical composition was analyzed by X-ray energy dispersive spectroscopy (EDS). The depth of the FTO structure and the surface roughness were measured by confocal laser scanning microscopy (CLSM). MC3T3-E1 cell adhesion proliferation and differentiation on the surface of each group of samples was assessed by immunofluorescence staining, CCK-8, and semiquantitative analysis of Alizarin staining. A freeze-drying method was applied to load recombinant human bone morphogenetic protein-2 (rhBMP-2), and an enzyme-linked immunosorbent assay (ELISA) was used to assess the drug-loading potential of different surface structures. @* Results@#SEM revealed that the surface of T group titanium plates showed uniform polishing marks in the same direction. The surface of the TO group was a nanoscale honeycomb-like titanium dioxide (TiO2) nanotube structure, and the FTO group formed a regular and ordered micro/nano layered structure. The contact angle of the FTO group was the smallest at 32° ± 1.7°. Its wettability was the best. The average depth of the first-level structure circular pores was 93.6 μm, and the roughness was 1.5-2 μm. The TO and FTO groups contained a high percentage of oxygen, suggesting TiO2 nanotube formation. The FTO group had the most significant surface cell proliferation (P<0.001) and the largest cell adhesion surface area (P<0.05). rhBMP-2 was slowly released for 14 d after loading in the FTO group and promoted extracellular matrix mineralization (P<0.001). @*Conclusion @#Titanium surface microprepared hierarchical structure has the effect of promoting MC3T3-E1 cell adhesion, proliferation, and osteogenic differentiation with drug loading potential, which is a new method of titanium surface treatment.

Effect of exosomes as drug carriers in chemotherapy of pancreatic cancer / 中南大学学报(医学版)

Pancreatic cancer (PC) is a malignant tumor of the digestive tract with poor patient prognosis. The PC incidence is still increasing with a 5-year survival rate of only 10%. At present, surgical resection is the most effective method to treat PC, however, 80% of the patients missed the best time for surgery after they have been diagnosed as PC. Chemotherapy is one of the main treating methods but PC is insensitive to chemotherapy, prone to drug resistance, and is accompanied by many side effects which are related to a lack of specific target. Exosomes are nanoscale vesicles secreted by almost all cell types and can carry various bioactive substances which mediate cell communication and material transport. They are characterized by a low immunogenicity, low cytotoxicity, high penetration potential and homing capacity, and possess the potential of being used as advanced drug carriers. Therefore, it is a hot research topic to use drug-loaded exosomes for tumor therapy. They may alleviate chemotherapy resistance, reduce side effects, and enhance the curative effect. In recent years, exosome drug carriers have achieved considerable results in PC chemotherapy studies.

Formulation optimization of emodin nanostructured lipid carriers by Box-Behnken response surface method and in vitro quality evaluation / 中国中药杂志

Emodin nanostructured lipid carriers(ED-NLC) were prepared and their quality was evaluated in vitro. Based on the results of single-factor experiments, the ED-NLC formulation was optimized by Box-Behnken response surface method with the dosages of emodin, isopropyl myristate and poloxamer 188 as factors and the nanoparticle size, encapsulation efficiency and drug loading as evaluation indexes. Then the evaluation was performed on the morphology, size and in vitro release of the nanoparticles prepared by emulsification-ultrasonic dispersion method in line with the optimal formulation, i.e., 3.27 mg emodin, 148.68 mg isopropyl myristate and 173.48 mg poloxamer 188. Under a transmission electron microscope(TEM), ED-NLC were spherical and their particle size distribution was uniform. The particle size of ED-NLC was(97.02±1.55) nm, the polymer dispersion index 0.21±0.01, the zeta potential(-38.96±0.65) mV, the encapsulation efficiency 90.41%±0.56% and the drug loading 1.55%±0.01%. The results of differential scanning calorimeter(DSC) indicated that emodin may be encapsulated into the nanostructured lipid carriers in molecular or amorphous form. In vitro drug release had obvious characteristics of slow release, which accorded with the first-order drug release equation. The fitting model of Box-Behnken response surface methodology was proved accurate and reliable. The optimal formulation-based ED-NLC featured concentrated particle size distribution and high encapsulation efficiency, which laid a foundation for the follow-up study of ED-NLC in vivo.

Effect of HSRP1 oxygen-carrying solution on early perfusion in rabbits with controlled severe hemorrhagic anemia / 中国输血杂志

【Objective】 To observe the effect of glutaraldehyde polymerized bovine hemoglobin injection (code: HSRP1) oxygen-carrying fluid on early perfusion of severe hemorrhagic anemia in rabbits. 【Methods】 The rabbit model of controlled severe hemorrhagic anemia was established. Twelve modeled rabbits were divided into glutaraldehyde polymerized bovine hemoglobin injection (code: HSRP1) group and sodium lactate ringer′s injection (LR) group, with 6 rabbits in each group(half male and half female). HSPR1 group and LR group were treated with HSRP1 and LR, respectively. The survival rate of experimental rabbits was observed, and the indexes of hemodynamics, venous blood gas, plasma hemoglobin, base surplus, lactic acid and bicarbonate were measured before and after blood loss, as well as each point within 24 h after infusion. 【Results】 The survival rate of HSRP1 group was significantly different from that of LR group (P<0.05); After exsanguination, the mean arterial pressure of each group was significantly different from that before exsanguination (P<0.05), but there was no significant difference between HSPR1 group and LR group after infusion; In the second stage of perfusion, the blood lactate concentration and base excess in the HSRP1 group were significantly different from those in the LR group at each time point (P<0.05), at 2 h after perfusion, the respiratory rate started to differ significantly from that of the LR group (P<0.05), heart rate was significantly different from LR group at 4 h after perfusion(P<0.05); There were no significant differences between HSRP1 group and LR group in plasma venous oxygen partial pressure, venous oxygen saturation and plasma hemoglobin at all time points. 【Conclusion】 HSPR1 is used for severe traumatic hemorrhagic shock in rabbits, and can improve the survival rate of experimental rabbits by providing oxygen to hypoxic tissues and correcting anaerobic metabolism. As a new oxygen-carrying fluid, HSPR1 can correct the oxygen supply balance of patients with severe hemorrhagicanemia in early stage.

Gestión de riesgo para la prevención primaria de tuberculosis en una entidad administradora de planes de beneficios en salud en Colombia / Risk management for the primary prevention of tuberculosis in an entity that administers health benefit plans in Colombia

RESUMEN Objetivo Diseñar y validar un modelo para la gestión del riesgo en salud, orientado a disminuir la incidencia de la tuberculosis en la población afiliada a las empresas administradoras de planes de beneficios colombianas (EAPB) desde la perspectiva de prevención primaria de la enfermedad. Métodos A partir de una reflexión inductiva, se diseñó un modelo de atención en tuberculosis orientado a coordinar acciones de gestión integral de riesgo en salud en el contexto de un modelo de aseguramiento fundamentado en la atención primaria en salud (APS). Se realizó una validación facial y de contenido del modelo con expertos temáticos en el programa de control de la tuberculosis de algunas EAPB y otros sectores. Resultados Se identificaron aspectos eje, fortalezas y oportunidades de mejora que se utilizaron como elementos centrales para el modelo, el cual se orienta a prevenir el desarrollo de la enfermedad, al tiempo que continúa promoviendo el seguimiento a los tratamientos y los procesos de rehabilitación. La revisión de expertos permitió validar y enriquecer el diseño planteado. Discusión La gestión del riesgo en salud es una responsabilidad asignada dentro del sistema de salud colombiano a las EAPB. El diseño del presente modelo aporta para que la gestión del riesgo se realice de manera organizada, definida y estandarizada, a fin de obtener mejores resultados en la prevención de la tuberculosis.

ABSTRACT Objective To design and valídate a model for health risk management, aimed at reducing the incidence of tuberculosis in the population affiliated with the Colombian Benefit Plan Administraron Companies (EAPB) from the perspective of primary prevention of the disease. Methods From an inductive reflection, a tuberculosis care model was designed aimed at coordinating comprehensive health risk management actions in the context of an assurance model based on primary care (PHC). A facial and content validation of the model was carried out with thematic experts in the tuberculosis control program of some EAPB and other sectors. Results Core aspects, strengths and opportunities for improvement were identified that were used as central elements for the model, which is aimed at preventing the development of the disease, while continuing to promote the follow-up of treatments and rehabilitation processes. The expert review allowed to validate and enrich the proposed design. Discussion Health risk management is a responsibility assigned within the Colombian health system to the EAPB. The design of this model contributes so that risk management is carried out in an organized, defined and standardized manner; seeking to obtain better results in the prevention of tuberculosis.

Significación de los marcadores infecciosos para identificar portadores de hepatitis B en donantes de sangre / Significance of hepatitis B surface antigen, IgM/IgG core antibody and hepatitis B virus DNA in blood donors

Resumen Introducción: La identificación de portadores del virus de la hepatitis B en donantes de sangre es imperativo para evitar la transmisión de la enfermedad a través de transfusiones sanguíneas. Objetivo: Determinar si los donantes de sangre con resultados positivos de los marcadores serológicos HbsAg y anti-HBc eran portadores de ADN del virus de la hepatitis B. Métodos: Se recolectaron 12 745 muestras de seis bancos de sangre ecuatorianos, las cuales fueron analizadas con pruebas serológicas para identificar los marcadores infecciosos HBsAg, anti-HBc, anti-HBs mediante prueba ELISA automatizada. Todas las muestras positivas para uno, dos o los tres marcadores fueron analizadas con técnica molecular para determinar la presencia de ADN viral. Resultados: Se identificó que 27.5 % de las muestras reactivas solo a anti-HBc y 100 % de las muestras con resultados positivos de HBsAg/anti-HBc-IgM/IgG presentaron ADN del virus de la hepatitis B (p = 0.001). Conclusiones: La elección de los marcadores de infección y los métodos de detección definen los resultados. Es importante la realización de dos pruebas serológicas y una molecular para identificar a los portadores del virus de la hepatitis B y evitar su transmisión.

Abstract Introduction: Identification of hepatitis B virus carriers in blood donors is imperative in order to avoid transmission of the disease via blood transfusion. Objective: To determine if blood donors with positive results for serological markers HBsAg and anti-HBc were hepatitis B virus DNA carriers. Methods: 12,745 samples were collected from six Ecuadorian blood banks and analyzed for HBsAg, anti-HBc and anti-HBs infectious markers by automated ELISA. All samples that tested positive for one, two or all three markers were analyzed with molecular techniques to determine the presence of viral DNA. Results: 27.5 % of the samples that were reactive for anti-HBc alone and 100 % of those with positive results for HbsAg and IgM/IgG anti-HBc were identified to contain hepatitis B virus DNA (p = 0.001). Conclusions: The selection of infection markers, as well as the detection methods define the results. Performing two serological and one molecular test is important in order to identify hepatitis B virus carriers and prevent its transmission.

Nanostructured lipid carriers as a novel tool to deliver sclareol: physicochemical characterisation and evaluation in human cancer cell lines

Sclareol (SC) is arousing great interest due to its cytostatic and cytotoxic activities in several cancer cell lines. However, its hydrophobicity is a limiting factor for its in vivo administration. One way to solve this problem is through nanoencapsulation. Therefore, solid lipid nanoparticles (SLN-SC) and nanostructured lipid carriers (NLC-SC) loaded with SC were produced and compared regarding their physicochemical properties. NLC-SC showed better SC encapsulation than SLN-SC and was chosen to be compared with free SC in human cancer cell lines (MDA-MB-231 and HCT-116). Free SC had slightly higher cytotoxicity than NLC-SC and produced subdiploid DNA content in both cell lines. On the other hand, NLC-SC led to subdiploid content in MDA-MB-231 cells and G2/M checkpoint arrest in HCT-116 cells. These findings suggest that SC encapsulation in NLC is a way to allow the in vivo administration of SC and might alter its biological properties

Medicamento como doença e biografia sorológica em comunidades virtuais de portadores de hepatite C / Medication as disease and serological biography in virtual communities of patients with hepatitis C

Resumo A hepatite C (HC) é uma doença que se agrava insidiosamente por décadas e com altas taxas de recidiva e cronificação. Seu tratamento com coquetel viricida origina reações colaterais violentas que comprometem o bem-estar dos portadores, sobretudo por não saberem como lidar com esses efeitos. Estudamos as postagens de uma comunidade virtual (CV) por meio de técnicas de análise de conteúdo orientadas por nuvens de palavras (NP). A partir do destaque nas postagens dos termos MEDICAMENTO e TRATAMENTO apontadas pelas NP, a leitura e análise do material mostrou o TRATAMENTO como ameaça, risco e agressão a reduzir qualidade de sobrevida; o "imperativo sorológico" como determinante categórico e inexorável de decisões clínicas; angústia e resignação no decorrer do acompanhamento entre as recidivas e marcação do tempo constituindo "biografias sorológicas". Concluímos que pacientes fisicamente distantes se apropriam da Web de modo gregário em CVs deixando uma rica narrativa terapêutica cuja análise representa um relevante recurso suplementar para a identificação de demandas subestimadas pelas práticas assistenciais.

Abstract Hepatitis C (HC) is a disease that worsens insidiously for decades and with high recurrence and chronicity rates. Its treatment with viricidal cocktail causes violent side reactions that compromise the well-being of patients, mainly because they do not know how to deal with these effects. We study the posts of a virtual community (VC) using content analysis techniques guided by word clouds (WC). The terms MEDICINE and TREATMENT was pointed out by the WC and the reading and analysis of the material showed TREATMENT as a threat, risk and aggression to reduce quality of survival; the "serological imperative" as a categorical and inexorable determinant of clinical decisions; anguish and resignation during the follow-up between relapses; and time pacing constituting "serological biographies". We conclude that distant patients appropriate the Web in a gregarious way in VCs, leaving a rich therapeutic narrative whose analysis represents a relevant supplementary resource for the identification of underestimated demands for care practices.

Effects of polyethylene glycol length on oral absorption of coumarin 6-loaded nanostructured lipid carrier / 中国药科大学学报

@#Polyethylene glycol (PEG) of different lengths were prepared to investigate their effects on oral absorption of nanostructured lipid carrier (NLCs).Three kinds of PEG-modified NLCs with different chain lengths, including polyethylene glycol (100) monostearate (S100), polyethylene glycol (55) monostearate (S55), polyethylene glycol (40) monostearate (S40), were prepared by film dispersion method.Coumarin 6 was chosen as a fluorescent probe to characterize the physicochemical properties of NLCs with different lengths.Meanwhile, the stability of NLCs in simulate buffer, the release behavior, cytotoxicity of NLCs, the uptake kinetics and cellular uptake mechanisms were evaluated. This work demonstrated that the thickness of the hydrated layer increased with the increase of PEG length. Of note, S100-modified NLCs (pNLC-EG100) exhibited higher cellular uptake efficiency compared with other formulations. Thus, S100 was optimized as the best molecular weight for PEG-modified NLCs on oral drug delivery system.

Intranasal delivery of nanostructured lipid carriers, solid lipid nanoparticles and nanoemulsions: A current overview of

The management of the central nervous system (CNS) disorders is challenging, due to the need of drugs to cross the blood‒brain barrier (BBB) and reach the brain. Among the various strategies that have been studied to circumvent this challenge, the use of the intranasal route to transport drugs from the nose directly to the brain has been showing promising results. In addition, the encapsulation of the drugs in lipid-based nanocarriers, such as solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) or nanoemulsions (NEs), can improve nose-to-brain transport by increasing the bioavailability and site-specific delivery. This review provides the state-of-the-art of

The reversed intra- and extracellular pH in tumors as a unified strategy to chemotherapeutic delivery using targeted nanocarriers

Solid tumors are complex entities, comprising a wide variety of malignancies with very different molecular alterations. Despite this, they share a set of characteristics known as "hallmarks of cancer" that can be used as common therapeutic targets. Thus, every tumor needs to change its metabolism in order to obtain the energy levels required for its high proliferative rates, and these adaptations lead to alterations in extra- and intracellular pH. These changes in pH are common to all solid tumors, and can be used either as therapeutic targets, blocking the cell proton transporters and reversing the pH changes, or as means to specifically deliver anticancer drugs. In this review we will describe how proton transport inhibitors in association with nanocarriers have been designed to block the pH changes that are needed for cancer cells to survive after their metabolic adaptations. We will also describe studies aiming to decrease intracellular pH in cancer using nanoparticles as molecular cages for protons which will be released upon UV or IR light exposure. Finally, we will comment on several studies that have used the extracellular pH in cancer for an enhanced cell internalization and tumor penetration of nanocarriers and a controlled drug delivery, describing how nanocarriers are being used to increase drug stability and specificity.

Formulation, Optimization And Characterization Of Nanostructured Lipid Carrier Of Nitrofurantoin

Nitrofurantoin is effective against many urinary tract pathogens. It acts as bacteriostatic and/or bactericidal by inhibiting DNA-RNA protein& cell wall synthesis. Nanostructured Lipid Carriers (NLCs) of NFT was prepared by Hot Homogenization Process. Glyceryl Monostearate and Miglyol 812 were heated at 80ºC temperature on hot plate. In the melted lipid, drug was added with continuous stirring at high speed homogenization. Formulation NLC12B has % Entrapment efficiency 89.1 ± 0.5, PDI 0.11 ± 0.01 and mean particle size 237 ± 7nm represents narrow particle size distribution. Spherical feature of NLCs with better uniformity without aggregation of Nitrofurantoin loaded NLC was confirmed by TEM. Moreover, efficient miscibility of drug in lipids was confirmed by the absence of intense and characteristic peak of NFT in XRPD. After 6 month storage at 2-8°C there was no significant changes in the PDI as well as mean particle size.

Preparation，optimization and antibacterial activity of luteolin nanostructured lipid carriers / 中国药科大学学报

@#To prepare and optimize luteolin nanostructured lipid carriers (Lut-NLCs) and investigate their antibacterial activity in vitro. Lut-NLCs were prepared by hot melt emulsification-ultrasonic method. The solid lipid concentration (X1),liquid lipid concentration (X2) and surfactant concentration (X3) were used as independent variables,with the average particle size (Y1) and the encapsulation efficiency (Y2) as the dependent variables. The optimal formulation of Lut-NLCs was obtained through Box-Behnken experiment design. The microstructure of Lut-NLCs was observed by transmission electron microscopy(TEM). The in vitro release characteristics of Lut-NLCs were investigated. Furthermore, the in vitro antibacterial activities of luteolin and Lut-NLCs were compared. The formulation composition of Lut-NLCs was optimized as follows:the concentration of the solid lipid, liquid lipid and surfactant were 13.0 mg/mL,15.0 mg/mL,and 15.0 mg/mL,respectively. Three batches of Lut-NLCs were prepared with an average particle size of (210.4±17.3) nm,and an encapsulation efficiency of (88.4±1.2)%. Lut-NLCs were observed to be spheroidal,with a smooth surface and a uniform particle size distribution by TEM. The drug release profiles of Lut-NLCs showed a bursting release in the early stage and a slow and stable release in the later stage. Moreover, the cumulative release amount of drug reached 95% in 12 hours. The results of antibacterial circle experiment showed that the antibacterial effect of Lut-NLCs on Staphylococcus aureus and Escherichia coli was higher than that of luteolin raw materials. In this study,the formulation of Lut-NLCs prepared by simple preparation process is reasonable,and Lut-NLCs also exhibited the significant in vitro antibacterial activity. It is expected to be an effective way for external application of luteolin.

Effect of Cilostazol-Loaded PCL/PEG Nanocapsules on Abdominal Aortic Tunics and Lipid Profile of Wistar Rats

Abstract Cilostazol (CLZ) is a phosphodiesterase III inhibitor with antiplatelet and vasodilator properties. It has been recently verified that CLZ plays a significant role in the arteries by inhibiting the proliferation and growth of muscle cells, increasing the release of nitric oxide by the endothelium and promoting angiogenesis. Considering these promising effects, the use of nanocapsules may be an interesting strategy to optimize its pharmacokinetics and pharmacodynamics at the vascular level for preventing atherosclerosis. The aim of this study was to evaluate the effect of cilostazol-loaded nanocapsules in the abdominal aortic tunics and on the lipid profile of Wistar rats in order to investigate its potential role in the prevention of atherosclerosis. Thirty-two animals were divided into four groups of eight animals, with 30-day treatment. Group 1 received nanoencapsulated CLZ; Group 2, control nanocapsules with no drug; Group 3, propylene glycol and water; and Group 4, a solution of CLZ in propylene glycol and water. After 30 days, there was no statistically significant difference between the groups regarding the cellularity and thickness of the arterial tunics of the abdominal aorta. However, the group that received nanoencapsulated CLZ (Group 1) had an improvement in HDL-c and triglyceride values compared to unloaded nanocapsules (Group 2).