Recent Progress of Nano-drug Combined with Chimeric Antigen Receptor T Cell Therapy in the Treatment of Soild Tumors / 中国肺癌杂志

Chimeric antigen receptor T cell (CAR-T) therapy has shown remarkable success in treating hematological malignancies. However, CAR-T therapy for solid tumors is still limited due to the unique solid-tumor microenvironment and heterogeneous target antigen expression, which leads to an urgent need of combining other therapies. At present, nano delivery system has become one of the most promising directions for the development of anti-tumor drugs. Based on the background of CAR-T and tumor treatment, we focus on the research progress of nanomedicine combined with CAR-T therapy, and systematically review the strategies and examples in recent years in the aspects of in vivo delivery of mRNA, regulation of tumor microenvironment, combination with photothermal therapy. And we also look forward to the future direction of this filed.
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Nanopartículas de plata contra bacterias presentes en biofilm dental de pacientes pediátricos / Silver nanoparticles against bacteria present in dental biofilm of pediatric patients

Introducción: el biofilm dental microbiano es el precursor de diversas enfermedades orales, una de ellas la caries, ésta representa la enferme- dad oral más significativa a nivel mundial, con una incidencia de 1.76 billones de niños afectados. Las nanopartículas de plata (AgNPs) se están usando como alternativa para el control y prevención del biofilm dental, ya que poseen propiedades antimicrobianas contra bacterias relacionadas a estas enfermedades. Sin embargo, no hay estudios que evalúen este comportamiento en pacientes pediátricos. Objetivo: eva- luar la actividad antimicrobiana de las AgNPs en bacterias de aislados clínicos tomados de pacientes pediátricos. Material y métodos: se tomó muestra del biofilm dental de 22 pacientes pediátricos, el efecto micro- biológico se evaluó mediante ensayos microbiológicos estandarizados internacionalmente por triplicado, usando dos diferentes tamaños de AgNPs. Resultados: los dos tamaños de AgNPs mostraron inhibición bacteriana, sin embargo, sólo se vio una diferencia estadísticamente significativa entre el género (p < 0.05), además, en general, hubo una correlación positiva significativa en relación a la concentración de las AgNPs y la velocidad del crecimiento bacteriano (p < 0.05). Conclusión: las AgNPs se pueden considerar como una alternativa para la prevención del biofilm dental y de esta manera para el control de diferentes enfermedades orales (AU))

Introduction: dental biofilm is the precursor of oral diseases, one of them dental caries, this represents the most significant oral disease worldwide with an incidence of 1.76 billion affected children. Silver nanoparticles (AgNPs) are being used as an alternative for the control and prevention of dental biofilm since they have antimicrobial properties against bacteria related to these diseases. However, there are no studies evaluating this behavior in pediatric patients. Objective: to evaluate the antimicrobial activity of AgNPs in bacteria from clinical isolates taken from pediatric patients. Material and methods: a sample of dental biofilm was taken from 22 pediatric patients, the microbiological effect was evaluated by international standardized microbiological tests in triplicate, using two different sizes of AgNPs. Results: the two sizes of AgNPs showed bacterial inhibition, however, only a statistically significant difference was seen between gender (p < 0.05), in addition, in general, there was a significant positive correlation in relation to the concentration of AgNPs and the speed bacterial growth (p < 0.05). Conclusion: AgNPs can be considered as an alternative for the prevention of dental biofilm and thus for the control of different oral diseases (AU)

Nanoparticle characterization of HOMOEO AGROCARE (Agro Homeopathic Drug) by HRTEM and EDS analysis

BackgroundHomeopathy as a therapeutic tool is still very nascent in plant science and agriculture. Therapies used for plant growth and diseases are not relevant for plants alone, but they also drastically influence the ecosystem of the organic world too. Pesticidesand chemical fertilizers was a boon during the initial phase of the green revolution around the world. Unfortunately, later they became the major reason for the chronic illnesses like cancers and a cause for soil degradation all over. The scenario demandsthe use of alternative models in agricultural practices in order to prevent diseases and to maintain the health status of the population. This is also very important to get rid ofthe damages done to the soil. AimsThe present study aimed at analyzing thematerial content of the agro-homeopathic drug, 'Homeo agrocare'. MethodologyHigh resolution transmission electron microscope (HRTEM) and Energy dispersion spectroscopy (EDS) wereused to evaluate the material content of the drug. DLS and HRTEM wereused for the analysis of control sample (Pharmaceutical grade alcohol). Results(1) Drug solution contains plenty of nanoparticles (NPs). (2) Size of NPs ranges between 4.99nm -93.09 nm. (3) Twenty elements were identified in fields studied. (4) No particles identified in the control sample by DLS and HRTEM analysis. Conclusion Study conclusively proved the presence of NPs of the original drug materials used in the 'Homoeo agrocare' drug solution.(AU)

Nanotechnology for the treatment of deep endometriosis: uptake of lipid core nanoparticles by LDL receptors in endometriotic foci

OBJECTIVE: Rapidly dividing cells in multiple types of cancer and inflammatory diseases undergo high low density lipoprotein (LDL) uptake for membrane synthesis, and coupling an LDL-like nanoemulsion, containing lipid nanoparticles (LDE) to a chemotherapeutic agent efficiently targets these cells without significant systemic effects. This was a prospective exploratory study that evaluated the uptake of a radioactively labeled LDE emulsion by receptors of endometriotic foci and the capacity of the LDE for cellular internalization. METHODS: The lipid profile of each patient was determined before surgery, and labeled LDE were injected into fourteen patients with intestinal or nonintestinal endometriosis. The radioactivity of each tissue sample (intestinal endometriosis, nonintestinal endometriosis, healthy peritoneum, or topical endometrium) was measured. RESULTS: The group with intestinal endometriosis presented higher levels of plasma LDL but lower LDE uptake by foci than the nonintestinal group, suggesting less cell division and more fibrosis. The uptake of LDE was highest in the topical endometrium, followed by the healthy peritoneum, and lowest in the endometriotic lesion. Since the endometriotic foci showed significant LDE uptake, there was likely increased consumption of LDL by these cells, similar to cells in cancers and inflammatory diseases. Plasma cholesterol levels had no influence on LDE uptake, which showed that the direct delivery of the nanoemulsion to target tissues was independent of serum lipoproteins. There were no significant differences in the parameters (p>0.01) because of the small sample size, but the findings were similar to those of previous studies. CONCLUSION: Nanotechnology is a promising therapeutic option for surgery and hormonal blockage for deep endometriosis, with a lower complication rate and no systemic side effects.

Using nanoparticles in medicine for liver cancer imaging

One of the most important types of liver cancer is hepatocellular carcinoma [HCC]. HCC is the fifth most common cancer, and its correct diagnosis is very important. For the quick diagnosis of HCC, the use of nanoparticles is helpful. The major applications of nanoparticles are in medicine for organ imaging. Two methods of liver imaging are X-ray computed tomography [CT] and magnetic resonance imaging [MRI]

In this review, we attempt to summarize some of the contrast agents used in imaging such as superparamagnetic iron oxide nanoparticles [SPIONs] and iron oxide nanoparticles [lONPs], various types of enhanced MRI for the liver, and nanoparticles like gold [AuNPs], which is used to develop novel CT imaging agents

Treatment of patients with aortic atherosclerotic disease with paclitaxel-associated lipid nanoparticles

OBJECTIVE: The toxicity of anti-cancer chemotherapeutic agents can be reduced by associating these compounds, such as the anti-proliferative agent paclitaxel, with a cholesterol-rich nanoemulsion (LDE) that mimics the lipid composition of low-density lipoprotein (LDL). When injected into circulation, the LDE concentrates the carried drugs in neoplastic tissues and atherosclerotic lesions. In rabbits, atherosclerotic lesion size was reduced by 65% following LDE-paclitaxel treatment. The current study aimed to test the effectiveness of LDE-paclitaxel on inpatients with aortic atherosclerosis. METHODS: This study tested a 175 mg/m2 body surface area dose of LDE-paclitaxel (intravenous administration, 3/3 weeks for 6 cycles) in patients with aortic atherosclerosis who were aged between 69 and 86 yrs. A control group of 9 untreated patients with aortic atherosclerosis (72-83 yrs) was also observed. RESULTS: The LDE-paclitaxel treatment elicited no important clinical or laboratory toxicities. Images were acquired via multiple detector computer tomography angiography (64-slice scanner) before treatment and at 1-2 months after treatment. The images showed that the mean plaque volume in the aortic artery wall was reduced in 4 of the 8 patients, while in 3 patients it remained unchanged and in one patient it increased. In the control group, images were acquired twice with an interval of 6-8 months. None of the patients in this group exhibited a reduction in plaque volume; in contrast, the plaque volume increased in three patients and remained stable in four patients. During the study period, one death unrelated to the treatment occurred in the LDE-paclitaxel group and one death occurred in the control group. CONCLUSION: Treatment with LDE-paclitaxel was tolerated by patients with cardiovascular disease and showed the potential to reduce atherosclerotic lesion size.

Advances in the use of nanocarriers for cancer diagnosis and treatment / Avanços na utilização de nanocarreadores no tratamento e no diagnóstico de câncer

ABSTRACT The use of nanocarriers as drug delivery systems for therapeutic or imaging agents can improve the pharmacological properties of commonly used compounds in cancer diagnosis and treatment. Advances in the surface engineering of nanoparticles to accommodate targeting ligands turned nanocarriers attractive candidates for future work involving targeted drug delivery. Although not targeted, several nanocarriers have been approved for clinical use and they are currently used to treat and/or diagnosis various types of cancers. Furthermore, there are several formulations, which are now in various stages of clinical trials. This review examined some approved formulations and discussed the advantages of using nanocarriers in cancer therapy.

RESUMO A utilização de nanocarreadores como sistemas de entrega de drogas para agentes terapêuticos ou de imagem pode aumentar as propriedades farmacológicas dos compostos normalmente utilizados no tratamento e diagnóstico de câncer. Avanços em engenharia de superfície de nanopartículas para a acomodação de ligantes alvo têm feito dos nanocarreadores candidatos atrativos para um futuro trabalho envolvendo entrega de droga direcionada. Embora não direcionados, muitos nanocarreadores terapêuticos foram aprovados para uso clínico no tratamento e/ou diagnóstico de vários tipos de câncer. Além disso, há várias outras formulações que se encontram agora em estágio de testes clínicos. Este artigo de revisão examinou algumas formulações aprovadas e discutiu as vantagens da utilização de nanocarreadores na terapia de câncer.

Nanomedicine and therapy of lung diseases / Nanomedicina e terapia de doenças pulmonares

The use of nanotechnology has significantly increased in different fields of science, including the development of drug delivery systems. Currently, the most modern pharmaceutical nanocarriers, such as liposomes, micelles, nanoemulsions and polymeric nanoparticles, demonstrate extremely useful properties from the point of view of drug therapy. In this context, the development of nanocarriers for pulmonary application has been much debated by the scientific community in recent decades. Although research on the use of nanoparticles for pulmonary application are still in the initial phase, the studies conducted to date suggest that the development of drug delivery systems for systemic or local treatment of diseases that affect the respiratory system may be promising.

O uso da nanotecnologia tem aumentado significativamente em diversas áreas da ciência. Entre elas, está o desenvolvimento de sistemas de liberação de medicamentos. Atualmente, os nanocarreadores farmacêuticos mais modernos, como os lipossomas, as micelas, as nanoemulsões e as nanopartículas poliméricas, demonstram propriedades extremamente úteis do ponto de vista farmacoterápico. Nesse contexto, o desenvolvimento de nanocarreadores para aplicação pulmonar tem sido um tema amplamente debatido pela comunidade científica nas últimas décadas. Embora as pesquisas sobre o uso de nanopartículas para aplicação pulmonar ainda estejam em fase inicial, estudos realizados até hoje sugerem que o delineamento de sistemas de liberação de medicamentos para o tratamento sistêmico ou local de doenças que afetam o sistema respiratório, pode ser promissor no desenvolvimento de novas terapias de doenças pulmonares.

Therapeutic mechanism of treating SMMC-7721 liver cancer cells with magnetic fluid hyperthermia using Fe2O3 nanoparticles

This study aimed to investigate the therapeutic mechanism of treating SMMC-7721 liver cancer cells with magnetic fluid hyperthermia (MFH) using Fe2O3 nanoparticles. Hepatocarcinoma SMMC-7721 cells cultured in vitro were treated with ferrofluid containing Fe2O3 nanoparticles and irradiated with an alternating radio frequency magnetic field. The influence of the treatment on the cells was examined by inverted microscopy, MTT and flow cytometry. To study the therapeutic mechanism of the Fe2O3 MFH, Hsp70, Bax, Bcl-2 and p53 were detected by immunocytochemistry and reverse transcription polymerase chain reaction (RT-PCR). It was shown that Fe2O3 MFH could cause cellular necrosis, induce cellular apoptosis, and significantly inhibit cellular growth, all of which appeared to be dependent on the concentration of the Fe2O3 nanoparticles. Immunocytochemistry results showed that MFH could induce high expression of Hsp70 and Bax, decrease the expression of mutant p53, and had little effect on Bcl-2. RT-PCR indicated that Hsp70 expression was high in the early stage of MFH (<24 h) and became low or absent after 24 h of MFH treatment. It can be concluded that Fe2O3 MFH significantly inhibited the proliferation of in vitro cultured liver cancer cells (SMMC-7721), induced cell apoptosis and arrested the cell cycle at the G2/M phase. Fe2O3 MFH can induce high Hsp70 expression at an early stage, enhance the expression of Bax, and decrease the expression of mutant p53, which promotes the apoptosis of tumor cells.

Evaluation and comparison of anti-Candida effect of heat cure polymethylmethacrylate resin enforced with silver nanoparticles and conventional heat cure resins: An in vitro study.

Recent years have been dominated by research in nano science. Dentistry is no exception and there is increased research on nanoparticles in dentistry. Complete dentures increase the carriage of Candida in healthy patients, and the proliferation of C. albicans can be associated with denture-induced stomatitis. Purpose: To evaluate the anti-Candida effect of heat cure denture base resins reinforced with Ag° in the ratio of 4:1, 3:1, 2:1 (Groups B, C, and D, respectively) to the weight of denture base resins. Materials and Methods: Ag° were synthesized by chemical reduction method, incorporated into the polymer powder according to the ratio for each group, subjected to polymerization and microbial assay was calculated for the reference C. albicans strains by agar diffusion method for the incubation period of 24 h. Results: Group D showed multifold decrease in the colony-forming units. Conclusion: The antimicrobial effect of silver could be used vividly in the denture base for immunocompromised and geriatric patients.

Nanotechnology in Dermatology

The scientific community and general public have been exposed to a series of achievements attributed to a new area of knowledge: Nanotechnology. Both abroad and in Brazil, funding agencies have launched programs aimed at encouraging this type of research. Indeed, for many who come into contact with this subject it will be clear the key role that chemical knowledge will play in the evolution of this subject. And even more, will see that it is a science in which the basic structure is formed by distilling different areas of inter-and multidisciplinary knowledge along the lines of new paradigms. In this article, we attempt to clarify the foundations of nanotechnology, and demonstrate their contribution to new advances in dermatology as well as medicine in general. Nanotechnology is clearly the future. .

Impact of Experimental Nano-HAP Pastes on Bovine Enamel and Dentin Submitted to a pH Cycling Model

This in vitro study evaluated the preventive potential of experimental pastes containing 10% and 20% hydroxyapatite nanoparticles (Nano-HAP), with or without fluoride, on dental demineralization. Bovine enamel (n=15) and root dentin (n=15) specimens were divided into 9 groups according to their surface hardness: control (without treatment), 20 Nanop paste (20% HAP), 20 Nanop paste plus (20% HAP + 0.2% NaF), 10 Nanop paste (10% HAP), 10 Nanop paste plus (10% HAP + 0.2% NaF), placebo paste (without fluoride and HAP), fluoride paste (0.2% NaF), MI paste (CPP-ACP, casein phosphopeptide-amorphous calcium phosphate), and MI paste plus (CPP-ACP + 0.2% NaF). Both MI pastes were included as commercial control products containing calcium phosphate. The specimens were treated with the pastes twice a day (1 min), before and after demineralization. The specimens were subjected to a pH-cycling model (demineralization–6-8 h/ remineralization-16-18 h a day) for 7 days. The dental subsurface demineralization was analyzed using cross-sectional hardness (kgf/mm 2 , depth 10-220 µm). Data were tested using repeated-measures two-way ANOVA and Bonferroni's test (p<0.05). The only treatment able to reduce the loss of enamel and dentin subsurface hardness was fluoride paste (0.2% NaF), which differed significantly from the control at 30- and 50-µm depth (p<0.0001). The other treatments were not different from each other or compared with the control. The experimental Nanop pastes, regardless of the addition of fluoride, were unable to reduce dental demineralization in vitro.

Este estudo in vitro avaliou o potencial de pastas experimentais contendo nanopartículas de hidroxiapatita a 10% e 20% (Nano-HAP), com ou sem fluoreto, na prevenção da desmineralização dentária. Espécimes de esmalte (n=15) e de dentina radicular (n=15) bovinos foram divididos em nove grupos de acordo com o valor de dureza superficial: controle (sem tratamento), pasta Nanop 20 (HAP 20%), pasta Nanop 20 plus (HAP 20% + NaF 0,2%), pasta Nanop 10 (HAP 10%), pasta Nanop 10 plus (HAP 10% + NaF 0,2%), pasta placebo (sem F e HAP), pasta fluoretada (NaF 0,2%), pasta MI (CPP-ACP, fosfopeptídio da caseína-fosfato de cálcio amorfo), e pasta MI plus (CPP-ACP + NaF 0,2%). As duas pastas MI foram inclusas como grupos controles comerciais contendo fosfato de cálcio. Os espécimes foram tratados com as pastas duas vezes ao dia (1 min), antes e após a desmineralização. Os espécimes foram submetidos a um modelo de ciclagem de pH (desmineralização 6-8 h/ remineralização 16-18 h por dia) durante sete dias. A desmineralização dentária de subsuperfície foi avaliada através da dureza longitudinal (kgf/mm 2 , profundidade de 10-220 µm). Os dados foram analisados utilizando ANOVA a dois critérios e teste de Bonferroni (p<0,05). O único tratamento capaz de reduzir a perda da dureza de subsuperfície do esmalte e da dentina foi a pasta fluoretada (NaF 0,2%), a qual diferiu significativamente do controle nas profundidades de 30 e 50 µm da superfície (p<0,0001). Os outros tratamentos não foram diferentes entre si ou quando comparados ao controle. As pastas experimentais Nanop, independentemente da presença de fluoreto, não foram capazes de reduzir a desmineralização dentária in vitro.

Desenvolvimento, caracterização, avaliação da estabilidade e da penetração cutânea de nanopartículas de ácido ursólico incorporadas em formulação cosmética / Development, characterization, evaluation of stability and skin penetration of ursolic acid nanoparticles incorporated in cosmetic formulation

A indústria cosmética tem investido em tecnologias inovadoras na busca de maior eficácia de seus produtos. A Nanotecnologia tem sido utilizada com o propósito de desenvolver formulações de menor risco de irritação cutânea e que promovam a liberação modificada do componente ativo. Este trabalho teve como objetivo geral desenvolvimento, caracterização e avaliação de nanopartículas de ácido ursólico incorporadas em formulação cosmética. Nesta pesquisa, para determinar a eficiência de encapsulação do AU (ácido ursólico) livre e nas nanopartículas poliméricas, foi validada uma metodologia que empregou a CLAE (Cromatografia em fase Líquida de Alta Eficiência) e os resultados obtidos indicaram boa reprodutibilidade do método e concordância entre os resultados obtidos, sendo a metodologia empregada na avaliação do AU livre e nanoparticulado. As nanopartículas contendo AU apresentaram características de potencial estabilidade química, obtendo eficiência de encapsulação de 80% de AU para as nanopartículas poliméricas e 100% para os carreadores lipídicos nanoestruturados. A caracterização físico-química das nanopartículas poliméricas contendo AU foi realizada determinando-se diâmetro da partícula (353,4 ± 1,4 nm), índice de polidispersividade (0,106 ± 0,008) e potencial zeta (-35,6 ± 1,2 mV). Os resultados obtidos para os carreadores lipídicos nanoestruturados contendo AU nas formulações foram: tamanho de partícula entre 125,3±40,4 e 237,4±62,7 nm, índice de polidispersividade entre 0,01 e 0,38 e potencial zeta entre -20,5±9,2 e -50,7±9,5 mV. Os resultados obtidos indicaram estabilidade das nanopartículas desenvolvidas. O resultado relativo ao planejamento fatorial para otimização dos agentes tensoativos revelou modelo matemático de segunda ordem para a previsão de valores de potencial zeta em função das concentrações de SDS. Dessa forma, foi possível a preparação de carreador lipídico nanoestruturado contendo reduzida concentração de SDS e valor de potencial zeta menor...

The cosmetic industry has invested in innovative technologies in search of greater effectiveness of their products. Nanotechnology has been used with this propose to reduce the risk of skin irritation by promoting the modified release of the active component. This study had as main objective development, characterization and evaluation of ursolic acid nanoparticles incorporated in cosmetic formulation. In this research, to determine the entrapment efficiency of UA (ursolic acid) free and in polymeric nanoparticles, a methodology was validated using HPLC (high performance liquid chromatography) and the results indicated good reproducibility of the method and agreement between the results, the methodology employed could be assessed in the evaluation of free and UA nanoparticles. Nanoparticles containing UA showed characteristics of potential chemical stability obtaining entrapment efficiency of 80% for UA polymer nanoparticles and 100% for the nanostructured lipid carriers. The physicochemical characterization of polymeric nanoparticles containing UA was accomplished by determining the particle diameter (353.4 ± 1.4 nm), polydispersity index (0.106 ± 0.008) and zeta potential (-35.6 ± 1.2mV). The results obtained for the nanostructured lipid carriers containing UA formulations were: particle size between 125.3±40.4 and 237.4±62.7 nm, polydispersity index between 0.01 and 0.38, and zeta potential between -20.5±9.2 and -50.7±9.5 mV. The results indicated stability of the developed nanoparticles. The result for the factorial design for optimization of surfactant revealed a quadratic effect of the independent variable sodium dodecyl sulfate in zeta potential. Thus, it was possible to prepare nanostructured lipid carrier containing reduced concentrations of SDS and zeta potential value of less than -40 mV. By means of the techniques of TG/DTG and DSC, was observed that the UA remained stable. Cosmetic formulations containing free ursolic acid (AUL) and incorporated...

Uso de metotrexato associado à nanopartícula rica em colesterol (LDE) para tratamento da aterosclerose / Use of methotrexate associated to a cholesterol-rich nanoparticle (LDE) for atherosclerosis treatment

O Metotrexato (MTX) é um fármaco utilizado como anti-inflamatório no tratamento da artrite reumatóide (AR). O risco de doença cardiovascular em pacientes com AR é menor quando tratados com MTX. Apesar dessa evidência, há poucos relatos da utilização de MTX para o tratamento da aterosclerose. Foi desenvolvida em nosso laboratório uma nanopartícula rica em colesterol (LDE), a qual é reconhecida pelos receptores da lipoproteína de baixa densidade (LDLr) após injeção na corrente sangüínea. A LDE concentra-se em células com hiperexpressão de LDLr, em processos proliferativos como a aterosclerose. Dessa maneira, a LDE pode ser utilizada como veículo para o direcionamento de fármacos contra essas células. A molécula de MTX foi latenciada e a modificação do fármaco aumentou a sua incorporação à LDE. A proposta desse estudo foi avaliar a eficácia de MTX associado à LDE (LDE-MTX) no tratamento da aterosclerose em coelhos além de investigar o efeito desse complexo na expressão de genes inflamatórios que participam do processo aterogênico. Para realização do estudo foram utilizados quatro grupos de 10 coelhos (raça New Zealand) cada, sendo que todos foram submetidos a uma dieta rica em colesterol por 8 semanas. Após as primeiras 4 semanas de dieta, os grupos foram tratados com LDE-MTX (grupo LDE-MTX), MTX comercial (grupo MTX comercial), LDE (grupo controle LDE) ou solução salina (grupo controle Salina), via endovenosa por 4 semanas. O grupo LDE-MTX não apresentou toxicidade ao longo do tratamento de acordo com os parâmetros utilizados, enquanto que o grupo MTX comercial apresentou uma queda acentuada de eritrócitos ao final do tratamento (p<0,001). A análise morfométrica macroscópica mostrou que os grupos LDE-MTX e MTX comercial reduziram as lesões ateroscleróticas quando comparados ao grupo controle Salina (66 e 76%, respectivamente) (p<0,001). Por microscopia, a camada íntima do arco aórtico e torácico foi reduzida nos grupos LDE-MTX (67% e 75%) e MTX comercial...

Methotrexate (MTX) is the most frequently used drug for rheumatoid arthritis treatment. The incidence of vascular disease in these patients is lower when treated with MTX. However, few studies have been done using MTX for atherosclerosis treatment. In previous studies, we showed that, after injection into blood stream, a cholesterol-rich nanoparticle (LDE) binds to low density lipoprotein receptors (LDLr) and concentrates in tissues with intense cell proliferation such as atherosclerosis. LDE may thus carry drugs directed against those tissues reducing the toxicity of chemotherapeutic agents. For stable association with LDE, a lipophylic methotrexate derivative was used. The purpose of this study was to test MTX associated to LDE (LDE-MTX) in rabbits with atherosclerosis and investigate their anti-inflammatory effects on inflammatory mediators. Atherosclerosis was induced in rabbits by cholesterol rich diet during eight weeks. After 4 weeks from the introduction of the atherogenic diet, 4 groups of 10 animals were treated with LDE-MTX (LDE-MTX group), commercial MTX (commercial MTX Group), LDE (LDE control group) and saline solulion (Saline control group). MTX dose in both preparations was 4mg/kg/week during 4 additional weeks. LDE-MTX group showed superior tolerability with pronouncedly lesser hematologic toxicity in comparison to commercial MTX (p< 0.001). By morphometric analysis, both LDE-MTX and commercial MTX treatment groups showed a pronounced reduction of lesion area compared with Saline control group (66-76% respectively) (p<0001). By microscopy, intimal width at aortic arch and thoracic segments was reduced by 67% and 75% in LDE-MTX group compared to Saline control group, respectively (p<0.05). Commercial MTX group showed a reduction of 81% and 92% at aortic arch and thoracic segments compared to Saline control group, respectively (p<0.05). Presence of macrophages in intima layer at aortic arch was reduced by 59% and 57% (p<0.001) in LDE-MTX and...

Tuberculosis experimental y nanopartículas de las drogas específicas / Experimental tuberculosis and nanoparticles of specific drugs

La tuberculosis (TB) sigue siendo un problema epidemiológico dificil de controlar, especialmente en los países en vías de desarrollo. Por ello, será bienvenido todo lo que implique una mejoría en su manejo. La incorporación de las nanopartículas a la medicina, producida en los últimos años, puede traer aparejada ventajas en su diagnóstico y tratamiento, así como un control en el número creciente de pacientes enfermos con gérmenes multirresistentes a las drogas específicas. Se actualiza en esta publicación que, en diversos países del mundo, animales de laboratorio, cobayos y ratones, inoculados por el Mycobacterium tuberculosis, tuvieron mejorías llamativas de su enfermedad o su esterilización después de ser tratados con las drogas específicas (Isoniacida, Rifampicina, Pirazinamida y Estreptomicina) suministradas como nanopartículas. No se han efectuado hasta ahora experimentos en tuberculosis humana, pero las posibilidades son promisorias. Las nanopartículas tienen varias ventajas terapéuticas: gran estabilidad, gran capacidad para conducir múltiples drogas, varias vías de administración (inhalatoria, oral, intravenosa y subcutánea). Esperamos que en un futuro próximo podamos asistir a mejoras en el manejo de la tuberculosis humana.

Tuberculosis (TB) continues to be a difficult to control epidemiologic problem, particularly in the developing countries. For such reason, anything that may imply an improvement in its management will be welcome. The adoption of nanoparticles by the medical science, over the last few years, may entail advantages regarding its diagnosis and treatment as well as a control of the increasing number of patients infected with specific drug multi-resistant germs. The present publication introduces the information that in several countries laboratory animals, guinea-pigs and mice, inoculated with Mycobacterium tuberculosis, either showed striking recoveries or the sterilization of their disease after being treated with the specific drugs (Isoniazid, Rifampycin, Pyrazinamide and Streptomycin) administered as nanoparticles. No experiments have been made to date in human tuberculosis but there exist promising possibilities. Nanoparticles have several therapeutic advantages: great stability, a large capacity to carry multiple drugs, different routes of administration (inhalatory,oral, intravenous and subcutaneous). We expect that in the near future we will be able to see an improvement in the management of human tuberculosis.

Alginate nanoparticles as antituberculosis drug carriers: formulation development, pharmacokinetics and therapeutic potential.

BACKGROUND: Reduction in the dosing frequency of antituberculosis drugs (ATDs) by applying drug delivery technology has the potential to improve the patient compliance in tuberculosis (TB). Alginate (a natural polymer) based nanoparticulate delivery system was developed for frontline ATDs (rifampicin, isoniazid, pyrazinamide and ethambutol). METHODS: Alginate nanoparticles were prepared by the controlled cation induced gelification method and administered orally to mice. The drug levels were analysed by high performance liquid chromatography (HPLC) in plasma/tissues. The therapeutic efficacy was evaluated in M. tuberculosis H37Rv infected mice. RESULTS: High drug encapsulation efficiency was achieved in alginate nanoparticles, ranging from 70%-90%. A single oral dose resulted in therapeutic drug concentrations in the plasma for 7-11 days and in the organs (lungs, liver and spleen) for 15 days. In comparison to free drugs (which were cleared from plasma/organs within 12-24 h), there was a significant enhancement in the relative bioavailability of encapsulated drugs. In TB-infected mice three oral doses of the formulation spaced 15 days apart resulted in complete bacterial clearance from the organs, compared to 45 conventional doses of orally administered free drugs. CONCLUSIONS: Alginate nanoparticles appear to have the potential for intermittent therapy of TB.