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1.
Braz. j. biol ; 83: e251219, 2023. graf
Article in English | LILACS, VETINDEX | ID: biblio-1345535

ABSTRACT

Abstract The most common form of psycho-social dysfunction is anxiety with depression being related closely without any age bar. They are present with combined state of sadness, confusion, stress, fear etc. Glyoxalase system contains enzyme named glyoxalase 1 (GLO1).It is a metabolic pathway which detoxifies alpha-oxo-aldehydes, particularly methylglyoxal (MG). Methylglyoxal is mainly made by the breakdown of the glycolytic intermediates, glyceraldehyde-3-phosphates and dihydroxyacetone phosphate. Glyoxylase-1 expression is also related with anxiety behavior. A casual role or GLO-1 in anxiety behavior by using viral vectors for over expression in the anterior cingulate cortex was found and it was found that local GLO-1 over expression increased anxiety behavior. The present study deals with the molecular mechanism of protective activity of eugenol against anxiolytic disorder. A pre-clinical animal study was performed on 42 BALB/c mice. Animals were given stress through conventional restrain model. The mRNA expression of GLO-1 was analyzed by real time RT-PCR. Moreover, the GLO-1 protein expression was also examined by immunohistochemistry in whole brain and mean density was calculated. The mRNA and protein expressions were found to be increased in animals given anxiety as compared to the normal control. Whereas, the expressions were decreased in the animals treated with eugenol and its liposome-based nanocarriers in a dose dependent manner. However, the results were better in animals treated with nanocarriers as compared to the compound alone. It is concluded that the eugenol and its liposome-based nanocarriers exert anxiolytic activity by down-regulating GLO-1 protein expression in mice.


Resumo A forma mais comum de disfunção psicossocial é a ansiedade intimamente relacionada com a depressão, sem qualquer barreira de idade. Elas estão presentes em um estado combinado de tristeza, confusão, estresse, medo etc. O sistema de glioxalase contém uma enzima chamada glioxalase 1 (GLO1). É uma via metabólica que desintoxica alfa-oxo-aldeídos, particularmente metilglioxal (MG). O metilglioxal é produzido principalmente pela quebra dos intermediários glicolíticos, gliceraldeído-3-fosfatos e fosfato de diidroxiacetona. A expressão da glioxalase 1 também está relacionada ao comportamento de ansiedade. Um papel casual ou GLO1 no comportamento de ansiedade usando vetores virais para superexpressão no córtex cingulado anterior foi encontrado e descobriu-se que a superexpressão local de GLO1 aumentava o comportamento de ansiedade. O presente estudo trata do mecanismo molecular da atividade protetora do eugenol contra o transtorno ansiolítico. Um estudo pré-clínico em animais foi realizado em 42 camundongos BALB / c. Os animais foram submetidos ao estresse por meio do modelo de contenção convencional. A expressão de mRNA de GLO1 foi analisada por RT-PCR em tempo real. Além disso, a expressão da proteína GLO1 também foi examinada por imuno-histoquímica em todo o cérebro e a densidade média foi calculada. Verificou-se que as expressões de mRNA e proteínas estavam aumentadas em animais que receberam ansiedade em comparação com o controle normal. Considerando que as expressões foram diminuídas nos animais tratados com eugenol e seus nanocarreadores baseados em lipossomas de forma dependente da dose. No entanto, os resultados foram melhores em animais tratados com nanocarreadores em comparação com o composto sozinho. Conclui-se que o eugenol e seus nanocarreadores baseados em lipossomas exercem atividade ansiolítica por regulação negativa da expressão da proteína GLO1 em camundongos.


Subject(s)
Animals , Rabbits , Eugenol/therapeutic use , Eugenol/pharmacology , Lactoylglutathione Lyase/antagonists & inhibitors , Anxiety/drug therapy , Liposomes , Mice, Inbred BALB C
2.
Biomédica (Bogotá) ; 42(1): 67-84, ene.-mar. 2022. tab, graf
Article in English | LILACS | ID: biblio-1374508

ABSTRACT

Introduction: Praziquantel (PZQ) is the only commercially available drug for schistosomiasis. The current shortage of alternative effective drugs and the lack of successful preventive measures enhance its value. The increase in the prevalence of PZQ resistance under sustained drug pressure is, therefore, an upcoming issue. Objective: To overcome the tolerance to PZQ using nanotechnology after laboratory induction of a Schistosoma mansoni isolate with reduced sensitivity to the drug during the intramolluscan phase. Materials and methods: Shedding snails were treated with PZQ doses of 200 mg/kg twice/ week followed by an interval of one week and then repeated twice in the same manner. The success of inducing reduced sensitivity was confirmed in vitro via the reduction of cercarial response to PZQ regarding their swimming activity and death percentage at different examination times. Results: Oral treatment with a single PZQ dose of 500 mg/kg in mice infected with cercariae with reduced sensitivity to PZQ revealed a non-significant reduction (35.1%) of total worm burden compared to non-treated control mice. Orally inoculated PZQ- encapsulated niosomes against S. mansoni with reduced sensitivity to PZQ successfully regained the pathogen's sensitivity to PZQ as evidenced by measuring different parameters in comparison to the non-treated infected animals with parasites with reduced sensitivity to PZQ. The mean total worm load was 1.33 ± 0.52 with a statistically significant reduction of 94.09% and complete eradication of male worms. We obtained a remarkable increase in the percentage reduction of tissue egg counts in the liver and intestine (97.68% and 98.56%, respectively) associated with a massive increase in dead eggs and the complete absence of immature stages. Conclusion: PZQ-encapsulated niosomes restored the drug sensitivity against laboratory- induced S. mansoni adult worms with reduced sensitivity to PZQ.


Introducción. El prazicuantel es el único fármaco disponible comercialmente para la esquistosomiasis. La escasez actual de medicamentos alternativos y la falta de medidas preventivas eficaces aumentan su valor. La creciente prevalencia de la resistencia al prazicuantel bajo una presión prolongada del fármaco es, por tanto, un tema emergente. Objetivos. Superar la tolerancia al prazicuantel mediante nanotecnología después de la inducción en laboratorio de un aislamiento de Schistosoma mansoni con sensibilidad reducida al fármaco durante la fase intramolusco. Materiales y métodos. Los caracoles que liberaban cercarias se trataron con prazicuantel en dosis de 200 mg/kg dos veces por semana, seguidas de un intervalo de una semana, y luego se repitieron dos veces de la misma manera. La inducción exitosa de la sensibilidad reducida se confirmó in vitro mediante la reducción de la reacción de las cercarias al prazicuantel con respecto a su actividad de natación y el porcentaje de muerte en diferentes momentos de examen. El éxito en inducir una menor sensibilidad se confirmó in vitro mediante la reducción de la reacción de las cercarias al prazicuantel. Resultados. El tratamiento oral con una dosis única de prazicuantel de 500 mg/kg en ratones infectados con cercarias con sensibilidad reducida al prazicuantel, reveló una reducción no significativa (35,1 %) de la carga total de gusanos en comparación con los ratones de control no tratados. Los niosomas encapsulados en prazicuantel inoculados por vía oral contra S. mansoni con sensibilidad reducida al prazicuantel, permitieron reestablecer con éxito la sensibilidad del patógeno al medicamento, como lo demostró la medición de diferentes parámetros en comparación con los animales infectados no tratados con parásitos con sensibilidad reducida a prazicuantel. La carga media total de gusanos fue de 1,33 ± 0,52, con una reducción estadísticamente significativa del 94,09 %, y la erradicación completa de los gusanos machos adultos. Se obtuvo un aumento notable en el porcentaje de reducción del recuento de huevos en el tejido del hígado y el intestino (97,68 % y 98,56 %, respectivamente), asociado con un aumento masivo de huevos muertos y ausencia total de estadios inmaduros. Conclusión. Los niosomas encapsulados en prazicuantel restauraron la sensibilidad al fármaco contra gusanos adultos de S. mansoni con sensibilidad reducida al prazicuantel inducida en el laboratorio.


Subject(s)
Praziquantel , Schistosoma mansoni , Drug Resistance , Liposomes
3.
Article in Chinese | WPRIM | ID: wpr-939632

ABSTRACT

Liposome is an ideal drug carrier with many advantages such as excellent biocompatibility, non-immunogenicity, and easy functionalization, and has been used for the clinical treatment of many diseases including tumors. For the treatment of tumors, liposome has some passive targeting capability, but the passive targeting effect alone is very limited in improving the drug enrichment in tumor tissues, and active targeting is an effective strategy to improve the drug enrichment. Therefore, active targeting liposome drug-carriers have been extensively studied for decades. In this paper, we review the research progresses on active targeting liposome drug-carriers based on the specific binding of the carriers to the surface of tumor cells, and summarize the opportunities, challenges and future prospects in this field.


Subject(s)
Drug Carriers/therapeutic use , Drug Delivery Systems , Humans , Liposomes/therapeutic use , Neoplasms/drug therapy
4.
Article in Chinese | WPRIM | ID: wpr-928205

ABSTRACT

Liposomes with precisely controlled composition are usually used as membrane model systems to investigate the fundamental interactions of membrane components under well-defined conditions. Hydration method is the most common method for liposome formation which is found to be influenced by composition of the medium. In this paper, the effects of small alcohol (ethanol) on the hydration of lipid molecules and the formation of liposomes were investigated, as well as its coexistence with sodium chloride. It was found that ethanol showed the opposite effect to that of sodium chloride on the hydration of lipid molecules and the formation of liposomes. The presence of ethanol promoted the formation of liposomes within a certain range of ethanol content, but that of sodium chloride suppressed the liposome formation. By investigating the fluorescence intensity and continuity of the swelled membranes as a function of contents of ethanol and sodium chloride, it was found that sodium chloride and ethanol showed the additive effect on the hydration of lipid molecules when they coexisted in the medium. The results may provide some reference for the efficient preparation of liposomes.


Subject(s)
Ethanol/pharmacology , Lipids , Liposomes
5.
Article in Chinese | WPRIM | ID: wpr-928124

ABSTRACT

The optimal prescription of tanshinone Ⅱ_A(TSN)-glycyrrhetinic acid(GA) solid lipid nanoparticles(GT-SLNs) was explored and evaluated in vivo and in vitro, and its effect on acne after oral administration was investigated. The preparation processing and prescription were optimized and verified by single factor and response surface methodology. The in vitro release of GA and TSN in GT-SLNs was determined by ultra-performance liquid chromatography(UPLC). The effect of GT-SLNs on acne was investigated by the levels of sex hormones in mice, ear swelling model, and tissue changes in sebaceous glands, and the pharmacokinetics was evaluated. The 24-hour cumulative release rates of GA and TSN in SLNs were 65.87%±5.63% and 36.13%±2.31% respectively. After oral administration of GT-SLNs and the mixture of GA and TSN(GT-Mix), the AUC_(0-t) and AUC_(0-∞) of TSN in GT-SLNs were 1.98 times and 4.77 times those in the GT-Mix group, respectively, and the peak concentration of TSN in the GT-SLNs group was 17.2 times that in the GT-Mix group. After intragastric administration of GT-SLNs, the serum levels of testosterone(T) and the ratio of testosterone to estradiol(T/E2) in the GT-SLNs group significantly declined, and the sebaceous glands of mice were atrophied to a certain extent. The results demonstrated that obtained GT-SLNs with good encapsulation efficiency and uniform particle size could promote the release of GA and TSN. GT-SLNs displayed therapeutic efficacy on acne manifested by androgen increase, abnormal sebaceous gland secretion, and inflammatory damage.


Subject(s)
Abietanes , Acne Vulgaris/drug therapy , Animals , Drug Carriers , Glycyrrhetinic Acid , Liposomes , Mice , Nanoparticles , Particle Size , Testosterone
6.
Electron. j. biotechnol ; 52: 30-34, July. 2021. ilus, tab, graf
Article in English | LILACS | ID: biblio-1283487

ABSTRACT

BACKGROUND: This study aimed to develop an amplification method of urea detection based on pHsensitive liposomes. RESULTS: The urease covalently immobilized on the magnetic particles and the pH-sensitive liposomes encapsulating ferricyanide were added to the cyclic-voltammeter cell solution where urea was distributed. The conversion of urea into carbonic acid seemed to induce a pH decrease that caused a reduction in the electrostatic repulsion between the headgroups of weakly acidic 1,2-dipalmitoyl-sn-glycero3-succinate. The reduction induced the liposomes to release potassium ferricyanide that was encapsulated inside. The effects of urea concentration and pH value were investigated. A specific concentration (0.5 mg/mL) of the urea solution was set to observe the response. The activity of urease was reversible with respect to the pH change between 7 and 5. The sensitivity of this detection was almost identical to the comparable techniques such as an enzyme-linked immunosorbent assay and a field-effect transistor. CONCLUSIONS: In summary, the methodology developed in this study was feasible as a portable, rapid, and sensitive method.


Subject(s)
Urea/analysis , Liposomes/chemistry , Urease/chemistry , Enzyme-Linked Immunosorbent Assay , Enzymes, Immobilized , Hydrogen-Ion Concentration
7.
Article in Chinese | WPRIM | ID: wpr-942249

ABSTRACT

OBJECTIVE@#To develop dexamethasone plus minocycline-loaded liposomes (Dex/Mino liposomes) and apply them to improve bioinert polyetheretherketone (PEEK) surface, which could prevent post-operative bacterial contamination, enhance ossification for physiologic osseointegration, and finally reduce implant failure rates.@*METHODS@#Dex/Mino liposomes were covalently grafted onto the PEEK surface using polydopamine (pDA) coating as a medium. Confocal laser scanning microscopy was used to confirm the binding of fluorescently labeled liposomes onto the PEEK substrate, and a microplate reader was used to semiquantitatively measure the average fluorescence intensity of fluorescently labeled liposome-decorated PEEK surfaces. Moreover, the mouse subcutaneous infection model and the beagle femur implantation model were respectively conducted to verify the bioactivity of Dex/Mino liposome-modified PEEK in vivo, by means of micro computed tomography (micro-CT) and hematoxylin and eosin (HE) staining analysis.@*RESULTS@#The qualitative and quantitative results of fluorescently labeled liposomes showed that, the red fluorescence intensity of the PEEK-pDA-lipo group was stronger than that of the PEEK-NF-lipo group (P < 0.05); the liposomes were successfully and uniformly decorated on the PEEK surfaces due to the pDA coating. After mouse subcutaneous implantation of PEEKs for 24 hours, HE staining results showed that the number of inflammatory cells in the PEEK-Dex/Mino lipo group were lower than that in the inert PEEK group (P < 0.05), indicating a lower degree of infection in the test group. These results suggested that the Mino released from the liposome-functionalized surface provided an effective bacteriostasis in vivo. After beagle femoral implantation of PEEK for 8 weeks, micro-CT results showed that the PEEK-Dex/Mino lipo group newly formed more continuous bone when compared with the inert PEEK group; HE staining results showed that more new bones were formed in the PEEK-Dex/Mino lipo group than in the inert PEEK group, which were firmly bonded to the functionalized PEEK surface and extended along the PEEK interface. These results suggested that the Dex released from the liposome-functionalized surface induced effective bone regeneration in vivo.@*CONCLUSION@#Dex/Mino liposome modification enhanced the bioactivity of inert PEEK, the functionalized PEEK with enhanced antibacterial and osseointegrative capacity has great potential as an orthopedic/dental implant material for clinical application.


Subject(s)
Animals , Benzophenones , Dogs , Ketones , Liposomes , Mice , Osseointegration , Polyethylene Glycols , Polymers , Surface Properties , X-Ray Microtomography
8.
Journal of Experimental Hematology ; (6): 1136-1140, 2021.
Article in Chinese | WPRIM | ID: wpr-888529

ABSTRACT

OBJECTIVE@#To evaluate the efficacy and safety of CHOP regimen based on doxorubicin hydrochloride liposome in the initial treatment of elderly patients with diffuse large B-cell lymphoma (DLBCL).@*METHODS@#Thirty-one patients with DLBCL treated from January 1, 2012 to December 31, 2019 were analyzed retrospectively, their median age was 83 (71-95) years old, and all of them were in Ⅲ-Ⅳ stage, including 17 cases who had international prognostic index (IPI) ≥ 3. The patients were treated with R-CHOP and CHOP regimens based on doxorubicin hydrochloride liposome. The efficacy and safety were evaluated during and after treatment.@*RESULTS@#A total of 219 chemotherapy cycles and 7 median cycles were performed in 31 patients. The overall response (OR) rate and complete remission (CR) rate was 80.7% (25/31) and 61.3% (19/31), respectively, as well as 2 cases (6.5%) stable, 4 cases (12.9%) progressive. The main toxicities were as follows: the incidence of grade Ⅲ -Ⅳ neutropenia was 29% (9/31); two patients (6.5%) developed degree Ⅰ-Ⅱ cardiac events, which were characterized by new degree Ⅰ atrioventricular block; there were no cardiac events requiring emergency treatment and discontinuation of chemotherapy. The 1-year, 2-year and 3-year overall survival rate was 83.9%, 77.4% and 61.3%, respectively. The 1-year, 2-year and 3-year progression-free survival rate was 77.4%, 64.5% and 61.3%, respectively.@*CONCLUSION@#The chemotherapy regimen based on doxorubicin hydrochloride liposome has better efficacy and higher cardiac safety for elderly patients with DLBCL.


Subject(s)
Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Humans , Liposomes/therapeutic use , Lymphoma, Large B-Cell, Diffuse/drug therapy , Prednisolone , Prednisone/therapeutic use , Retrospective Studies , Rituximab/therapeutic use , Vincristine/therapeutic use
9.
Article in Chinese | WPRIM | ID: wpr-828886

ABSTRACT

OBJECTIVE@#To prepare warangalone-loaded thermosensitive liposomes (WLTSL) and evaluate its inhibitory effect on breast cancer cells .@*METHODS@#MTT assay was used to assess the changes in proliferation of 3 breast cancer cell lines (MDA-MB-231, MCF7, and SKBR3) following treatment with warangalone, soy isoflavone and genistein. Colony-forming assay and wound healing assay was used to assess colony forming activity and migration of MDA-MB-231 cells treated with warangalone. The effect of warangalone on the expression of MMP2 and MMP9 in MDA-MB-231 cells was examined with Western blotting. The thermosensitive liposomes (TSL) and WLTSL were prepared using a thin film hydration method, and the morphology, size, encapsulation efficiency and stability of the prepared liposomes were characterized using transmission electron microscopy, dynamic light scattering scanning and UV spectrophotometry. MTT assay was used to examine the inhibitory effect of WLTSL on mouse breast cancer cells (4T1) .@*RESULTS@#Warangalone showed stronger anti-proliferation effects than soy isoflavones and genistein in the 3 human breast cancer cell lines and significantly inhibited colony formation by MDA-MB-231 cells. Treatment with warangalone significantly inhibited migration of the breast cancer cells and down-regulated the cellular expressions of MMP2 and MMP9. The prepared TSL and WLTSL presented with a homogeneous, irregular spherical morphology, with a mean particle size of 56.23±0.61 nm, a polymer dispersity index of 0.241±0.014, a Zeta potential of -40.40±0.46 mV, and an encapsulation efficiency was 87.68±2.41%. WLTSL showed a good stability at 4 ℃ and 37 ℃ and a stronger inhibitory effect than warangalone in 4T1 cells.@*CONCLUSIONS@#Warangalone inhibits the proliferation, migration and invasion of breast cancer cells, and the prepared WLTSL possesses good physical properties and strong anti-breast cancer activity.


Subject(s)
Animals , Breast Neoplasms , Cell Line, Tumor , Cell Movement , Cell Proliferation , Humans , Isoflavones , Liposomes , Mice
10.
Braz. J. Pharm. Sci. (Online) ; 56: e18601, 2020. tab, graf
Article in English | LILACS | ID: biblio-1249143

ABSTRACT

The objective of this work was to develop and characterize liposomes loaded with silver nanoparticles (LAgNPs) to show improvement in stability characteristics. AgNPs were prepared by the green synthesis method with Aloe vera gel extract and exposure to sunlight. Liposomes were prepared by the modified reverse phase method. Particle size, polydispersity index, zeta potential, as well as the scanning electron microscopy (SEM) morphological aspects of AgNPs and LAgNPs were evaluated. In addition, was used flame atomic absorption spectroscopy to determine the amount of AgNP that was encapsulated in liposomes. The AgNPs presented as amorphous and polydisperse structures, with a mean diameter of 278.46 nm and zeta potential of -18.3 mV. LAgNPs had a mean diameter between 321 and 373 nm, the polydispersity index close to 0.2 and a zeta potential around -40 mV, which indicates greater stability to the AgNPs. The images obtained by SEM show semicircular structures for AgNPs and well-defined spherical shape for LAgNPs. The percentage of encapsulation was between 51.81 to 58.83%. These results showed that LAgNPs were obtained with adequate physicochemical characteristics as a release system.


Subject(s)
Silver , Nanoparticles/analysis , Liposomes/analysis , Sunlight/adverse effects , Microscopy, Electron, Scanning/methods , Spectrophotometry, Atomic/methods , Aloe/classification , Methods
11.
Braz. J. Pharm. Sci. (Online) ; 56: e17808, 2020. tab, graf
Article in English | LILACS | ID: biblio-1089231

ABSTRACT

This study evaluated the incorporation of tetracaine into liposomes by RSM (Response Surface Methodology) and ANN (Artificial Neural Networks) based models. RCCD (rotational central composite design) and ANN were performed to optimize the sonication conditions of particles containing 100 % lipid. Laser light scattering was used to perform measure hydrodynamic radius and size distribution of vesicles. The liposomal formulations were analyzed by incorporating the drug into the hydrophilic phase or the lipophilic phase. RCCD and ANN were conducted, having the lipid/cholesterol ratio and concentration of tetracaine as variables investigated and, the encapsulation efficiency and mean diameter of the vesicles as response variables. The optimum sonication condition set at a power of 16 kHz and 3 minutes, resulting in sizes smaller than 800 nm. Maximum encapsulation efficiency (39.7 %) was obtained in the hydrophilic phase to a tetracaine concentration of 8.37 mg/mL and 79.5:20.5% lipid/cholesterol ratio. Liposomes were stable for about 30 days (at 4 ºC), and the drug encapsulation efficiency was higher in the hydrophilic phase. The experimental results of RCCD-RSM and ANN techniques show ANN obtained more refined prediction errors that RCCD-RSM technique, therefore, ANN can be considered as an efficient mathematical method to characterize the incorporation of tetracaine into liposomes.


Subject(s)
Tetracaine/analysis , Liposomes/metabolism , Pharmaceutical Preparations/analysis , Efficiency/classification , Methodology as a Subject
12.
J. venom. anim. toxins incl. trop. dis ; 26: e20200032, 2020. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1135160

ABSTRACT

Liposomes are highly useful carriers for delivering drugs or antigens. The association of glycosylphosphatidylinositol (GPI)-anchored proteins to liposomes potentially enhances the immunogenic effect of vaccine antigens by increasing their surface concentration. Furthermore, the introduction of a universal immunoglobulin-binding domain can make liposomes targetable to virtually any desired receptor for which antibodies exist. Methods: We developed a system for the production of recombinant proteins with GPI anchors and histidine tags and Strep-tags for simplified purification from cells. This system was applied to i) the green fluorescent protein (GFP) as a reporter, ii) the promising Plasmodium falciparum vaccine antigen PfRH5 and iii) a doubled immunoglobulin Fc-binding domain termed ZZ from protein A of Staphylococcus aureus. As the GPI-attachment domain, the C-terminus of murine CD14 was used. After the recovery of these three recombinant proteins from Chinese hamster ovary (CHO) cells and association with liposomes, their vaccine potential and ability to target the CD4 receptor on lymphocytes in ex vivo conditions were tested. Results: Upon immunization in mice, the PfRH5-GPI-loaded liposomes generated antibody titers of 103 to 104, and showed a 45% inhibitory effect on in vitro growth at an IgG concentration of 600 µg/mL in P. falciparum cultures. Using GPI-anchored ZZ to couple anti-CD4 antibodies to liposomes, we created immunoliposomes with a binding efficiency of 75% to CD4+ cells in splenocytes and minimal off-target binding. Conclusions: Proteins are very effectively associated with liposomes via a GPI-anchor to form proteoliposome particles and these are useful for a variety of applications including vaccines and antibody-mediated targeting of liposomes. Importantly, the CHO-cell and GPI-tagged produced PfRH5 elicited invasion-blocking antibodies qualitatively comparable to other approaches.(AU)


Subject(s)
Plasmodium falciparum , Vaccines , Glycosylphosphatidylinositols , Liposomes , Antigens
13.
Braz. j. med. biol. res ; 52(3): e8281, 2019. tab, graf
Article in English | LILACS | ID: biblio-989461

ABSTRACT

It has been hypothesized that the therapeutic effects of artepillin C, a natural compound derived from Brazilian green propolis, are likely related to its partition in the lipid bilayer component of biological membranes. To test this hypothesis, we investigated the effects of the major compound of green propolis, artepillin C, on model membranes (small and giant unilamelar vesicles) composed of ternary lipid mixtures containing cholesterol, which display liquid-ordered (lo) and liquid-disordered (ld) phase coexistence. Specifically, we explored potential changes in relevant membrane parameters upon addition of artepillin C presenting both neutral and deprotonated states by means of small angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), and confocal and multiphoton excitation fluorescence microscopy. Thermotropic analysis obtained from DSC experiments indicated a loss in the lipid cooperativity of lo phase at equilibrium conditions, while at similar conditions spontaneous formation of unilamellar vesicles from SAXS experiments showed that deprotonated artepillin C preferentially located at the surface of the membrane. Time-resolved experiments using fluorescence microscopy showed that at doses above 100 µM, artepillin C in its neutral state interacted with both liquid-ordered and liquid-disordered phases, inducing curvature stress and promoting dehydration at the membrane interface.


Subject(s)
Phenylpropionates/chemistry , Lipid Bilayers/chemistry , Liposomes/chemistry , Reference Values , Temperature , Time Factors , Calorimetry, Differential Scanning , Cholesterol/chemistry , Reproducibility of Results , Microscopy, Confocal , Scattering, Small Angle , Laurates , Microscopy, Fluorescence , Models, Chemical , 2-Naphthylamine/analogs & derivatives
14.
Article in English | WPRIM | ID: wpr-765123

ABSTRACT

BACKGROUND: Nanoparticle-mediated photothermal therapy (PTT) has been well studied as a treatment for cancer. However, the therapeutic outcome of PTT is often hindered by the penetration depth of laser light. In the tumor margin beyond the laser penetration limit, tumor recurrence often occurs, bypassing the immune response of the host. Accumulating evidence suggests the prominent role of tumor microenvironment (TME) and its interactions with the immune components contribute to an immunosuppressive milieu during the post-therapy period. Here, we explored the immunosuppressive cascade generated after PTT, which is responsible for tumor recurrence, and identified the potential targets to achieve an effective PTT period. METHODS: Here, we investigated the immunosuppressive cascade generated after PTT in a CT26 tumor bearing mouse. The liposomal system loaded with the indocyanine green (ICG) was utilized for the generation of PTT with high efficiency. Immunological factors such as cytokines and protein expressions post-therapy were investigated through enzyme-linked immunosorbent assay, flow cytometry and western blot analysis. RESULTS: Our results suggested that PTT with ICG-loaded liposomes (Lipo-ICG) was effective for the first 5 days after treatment, resulting in tumor suppression. However, an immunosuppressive and pro-inflammatory environment developed thereafter, causing the recruitment and upregulation of the immune evasion factors of heat shock protein 70, programmed death ligand 1, indoleamine-dioxygenase, interleukin-6, transforming growth factor-β, regulatory T-cells, and myeloid-derived suppressor cells, to develop immunotolerance. CONCLUSION: Collectively, these findings have determined potential therapeutic targets to modulate the TME during PTT and achieve tumor ablation without remission.


Subject(s)
Animals , Blotting, Western , Cytokines , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , HSP70 Heat-Shock Proteins , Immune Evasion , Immunologic Factors , Immunosuppression Therapy , Indocyanine Green , Interleukin-6 , Liposomes , Mice , Recurrence , T-Lymphocytes, Regulatory , Tumor Microenvironment , Up-Regulation
15.
Article in Chinese | WPRIM | ID: wpr-774596

ABSTRACT

Hypertrophic scar( HS) is a very common skin fibrosis disorder after human skin injury and wound healing. The objective of this study was to investigate the efficacy of cell penetrating peptide TAT-modified liposomes loaded with salvianolic acid B( SAB-TAT-LIP) on proliferation,migration and cell cycle of human skin fibroblasts( HSF),and preliminarily evaluate its effect on prevention and treatment of HS. HSF were cultured in vitro,and MTT assay was used to detect the inhibitory effect of SAB-TAT-LIP on cell proliferation. Cell migration was assessed by Transwell chamber method and scratch method; and cell cycle change was detected by flow cytometry. In vitro cell studies showed that blank liposome basically had no toxic effect on HSF. Different concentrations of SABTAT-LIP inhibited proliferation on HSF in varying degrees after intervention for different periods in a dose and time dependent manner;meanwhile,SAB-TAT-LIP significantly inhibited the migration and invasion of HSF. At the same time,SAB-TAT-LIP could block the cell cycle at G0/G1 phase after intervention for 48 h,P<0.01 as compared with the blank control group. Conclusively,our experimental data quantitatively demonstrate that SAB-TAT-LIP has significant inhibitory effect on cells proliferation,invasion and migration,with blocking effect on G0/G1 phase. This may offer a promising therapeutic strategy for transdermal delivery in prevention and treatment of HS.


Subject(s)
Benzofurans , Pharmacology , Cell Cycle , Cell Movement , Cell Proliferation , Cell-Penetrating Peptides , Cells, Cultured , Drug Carriers , Fibroblasts , Cell Biology , Humans , Liposomes , Skin , Cell Biology
16.
Article in Chinese | WPRIM | ID: wpr-774547

ABSTRACT

In order to increase the stability and solubility of essential oil in Jieyu Anshen Formula, this study was to prepare the essential oil into liposomes. In this experiment, the method for the determination of encapsulation efficiency of liposomes was established by ultraviolet spectrophotometer and dextran gel column. The encapsulation efficiency and particle size of liposomes were used as evaluation indexes for single factor investigation and Box-Behnken design-response surface method was used to optimize the design. Then the optimal formulation of volatile oil liposome was characterized using methyleugenol, elemin, β-asarone and α-asarone as index components. Finally, the in vitro transdermal properties of liposomes were studied by modified Franz diffusion cell. The results showed that the concentration of lecithin, the mass ratio of lecithin to volatile oil, and the stirring speed were the three most significant factors affecting the liposome preparation. The optimum formulation of volatile oil liposome was as follows: the concentration of lecithin was 7 g·L~(-1); mass ratio of lecithin to volatile oil was 5∶1; and the stirring speed was 330 r·min~(-1). Under such conditions, the prepared liposomes had blue emulsion light, good fluidity, half translucent, with particle size of(102.6±0.35) nm, Zeta potential of(-17.8±0.306) mV, permeability of(1.67±1.01)%, and stable property if liposome was stored at 4 ℃. 24 h after percutaneous administration, the cumulative osmotic capacity per unit time was(30.485 2±1.238 9),(34.794 8±0.928 3),(26.677 1±1.171 7),(3.066 2±0.175 3) μg·cm~(-2)respectively for methyleugenol, elemin, β-asarone and α-asarone. In vitro transdermal behaviors of methyleugenol, elemin, β-asarone and α-asarone in liposomes were all consistent with Higuchi equation. The prepared volatile oil liposomes met the relevant quality requirements, providing a reference for further research on preparation of multi-component Chinese medicine essential oil liposomes.


Subject(s)
Administration, Cutaneous , Drugs, Chinese Herbal , Liposomes , Oils, Volatile , Particle Size , Solubility
17.
Article in English | WPRIM | ID: wpr-786671

ABSTRACT

BACKGROUND: Macrophages have been known to have diverse roles either after tissue damage or during the wound healing process; however, their roles in flap wound healing are poorly understood. In this study, we aimed to evaluate how macrophages contribute to the flap wound regeneration.METHODS: A murine model of a pedicled flap was generated, and the time-course of the wound healing process was determined. Especially, the interface between the flap and the residual tissue was histopathologically evaluated. Using clodronate liposome, a macrophage-depleting agent, the functional role of macrophages in flap wound healing was investigated. Coculture of human keratinocyte cell line HaCaT and monocytic cell line THP-1 was performed to unveil relationship between the two cell types.RESULTS: Macrophage depletion significantly impaired flap wound healing process showing increased necrotic area after clodronate liposome administration. Interestingly, microscopic evaluation revealed that epithelial remodeling between the flap tissue and residual normal tissue did not occurred under the lack of macrophage infiltration. Coculture and scratch wound healing assays indicated that macrophages significantly affected the migration of keratinocytes.CONCLUSION: Macrophages play a critical role in the flap wound regeneration. Especially, epithelial remodeling at the flap margin is dependent on proper macrophage infiltration. These results implicate to support the cellular mechanisms of impaired flap wound healing.


Subject(s)
Cell Line , Clodronic Acid , Coculture Techniques , Humans , Keratinocytes , Liposomes , Macrophages , Regeneration , Surgical Flaps , Wound Healing , Wounds and Injuries
18.
Article in English | WPRIM | ID: wpr-786485

ABSTRACT

Liposome is one of the oldest yet most successful nanomedicine platforms. Doxil®, PEGylated liposome loaded with doxorubicin (DOX), was approved by the FDA in 1995 for the treatment of AIDS-related Kaposi's sarcoma, and it was the first approval for nanomedicine. Since then, liposome-based therapeutics were approved for the treatment of various diseases and many clinical trials are underway. The success of the liposome-based therapeutics was due to following factors: (1) ease of synthesis, (2) biocompatibility, (3) the ability to load both hydrophilic and hydrophobic agents, and (4) long circulation property after application of polyethylene glycol (PEG). Recently, more functionalities are introduced to liposome platform, which are (1) in vivo imaging probes for optical, magnetic resonance imaging (MRI), positron emission tomography (PET), and single-photon emission computed tomography (SPECT), (2) pH and temperature-sensitive lipid moiety, and (3) novel agents for photodynamic and photothermal therapies (PDT, PTT). These conventional and newly tested advantages make the liposome to be one of the most promising nanoplatforms for theranostics.


Subject(s)
Doxorubicin , Hydrogen-Ion Concentration , Liposomes , Magnetic Resonance Imaging , Nanomedicine , Polyethylene Glycols , Positron-Emission Tomography , Sarcoma, Kaposi , Theranostic Nanomedicine , Tomography, Emission-Computed
19.
Article in English | WPRIM | ID: wpr-761763

ABSTRACT

In this study, we carried out extensive in vitro studies on various concentrations of tioxolone along with benzoxonium chloride and their niosomal forms against Leishmania tropica. Niosomes were prepared by the hydration method and were evaluated for morphology, size, release study, and encapsulation efficiency. This study measured leishmanicidal activity against promastigote and amastigote, apoptosis and gene expression levels of free solution and niosomal-encapsulated tioxolone along with benzoxonium chloride. Span/Tween 60 niosome had good physical stability and high encapsulation efficiency (more than 97%). The release profile of the entrapped compound showed that a gradual release rate. The combination of niosomal forms on promastigote and amastigote were more effective than glucantime. Also, the niosomal form of this compound was significantly less toxic than glucantime (P≤0.05). The flowcytometric analysis on niosomal form of drugs showed that higher number of early apoptotic event as the principal mode of action (89.13% in 200 μg/ml). Also, the niosomal compound increased the expression level of IL-12 and metacaspase genes and decreased the expression level of the IL-10 gene, which further confirming the immunomodulatory role as the mechanism of action. We observed the synergistic effects of these 2 drugs that induced the apoptotic pathways and also up regulation of an immunomodulatory role against as the main mode of action. Also, niosomal form of this combination was safe and demonstrated strong anti-leishmaniasis effects highlights further therapeutic approaches against anthroponotic cutaneous leishmaniasis in future planning.


Subject(s)
Apoptosis , Gene Expression , In Vitro Techniques , Interleukin-10 , Interleukin-12 , Leishmania tropica , Leishmania , Leishmaniasis, Cutaneous , Liposomes , Methods , Up-Regulation
20.
Article in Chinese | WPRIM | ID: wpr-941836

ABSTRACT

OBJECTIVE@#Larotaxel is a new chemical structure drug, which has not been marketed worldwide. Accordingly, the standard identification and quantification methods for larotaxel remain unclear. The spectrometric analyses were performed for verifying weight molecular formula, molecular weight and chemical structure of larotaxel. Besides, a quantification method was developed for measuring larotaxel in the liposomes.@*METHODS@#The molecular formula, molecular weight and chemical structure of larotaxel were studied by using mass spectrometry (MS), infra-red (IR), nuclear magnetic resonance (NMR) and ultraviolet-visible (UV-vis) spectrometric techniques. The absorption wavelength of larotaxel was investigated by UV-vis spectrophotometry full-wavelength scanning. Besides, a quantification method was developed by high performance liquid chromatography (HPLC), and then validated by measuring the encapsulation efficacy of larotaxel liposomes.@*RESULTS@#The four spectral characteristics of larotaxel were revealed and the corresponding standard spectra were defined. It was confirmed that larotaxel had the structure of tricyclic diterpenoids, with the molecular formula of C45H53NO14, the molecular weight of 831.900 1, and the maximum absorption wavelength of 230 nm. The quantitative method of larotaxel was established by using HPLC with a reversed phase C18 column (5 μm, 250 mm×4.6 mm), a mobile phase of acetonitrile-water (75:25, volume/volume), and a detection wavelength of 230 nm. The validation study exhibited that the established HPLC method was stable, and had a high recovery and precision in the quantitative measurement of larotaxel in liposomes. In addition, a new kind of larotaxel liposomes was also successfully prepared. The particle size of the liposomes was about 105 nm, with an even size distribution. And the encapsulation efficiency of larotaxel in the liposomes was above 80%.@*CONCLUSION@#The present study offers reference standard spectra of larotaxel, including MS, IR, NMR, and UV-vis, and confirms the molecular formula, molecular weight and chemical structure of larotaxel. Besides, the study develops a rapid HPLC method for quality control of larotaxel liposomes.


Subject(s)
Chromatography, High Pressure Liquid , Liposomes , Magnetic Resonance Spectroscopy , Taxoids
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