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1.
Journal of Pharmaceutical Practice ; (6): 12-17, 2024.
Article in Chinese | WPRIM | ID: wpr-1005421

ABSTRACT

Objective To prepare polymersomes (PSs) by block copolymers,evaluate their membrane structural stability,investigate the H+ transmembrane permeability of PSs and the impact of 1,4-dioxane and establish a foundation for drug encapsulation within polymersomes. Methods PSs were self-assembled by a block copolymer, PEG-PLGA, in a solvent solution. The pH-sensitive fluorescence probe HPTS was employed to examine the H+ transmembrane properties of PSs and compare them with PSs prepared using PBD-b-PEO, PS-b-PEO, and liposomes. The effect of varying concentrations of 1,4-dioxane on PSs’ membrane permeability properties was also investigated. Results The fluorescence excitation spectra of HPTS exhibited pH dependency, which showed a linear correlation between extravesicular H+ concentration and t1/2. Significant differences were observed in the membrane permeability capabilities of PSs with different membrane wall thicknesses. Compared to liposomes, the H+ transmembrane coefficients for the three types of PSs were reduced by 2.39×104, 3.38×104, and 5.48×108 times, respectively. 1,4-dioxane was found to modulate the permeability of PSs’ membranes, which displayed a concentration-dependent relationship. Conclusion PSs exhibited significantly lower membrane permeability compared to liposomes, indicating superior stability. 1,4-dioxane was identified as a modulator of PSs’ permeability, which offered potential for drug loading and release within PSs.

2.
Chinese Journal of Biologicals ; (12): 518-2023.
Article in Chinese | WPRIM | ID: wpr-996364

ABSTRACT

@#Objective To explore the physical and chemical properties of electric charge modified liposomes and the immune enhancement effect as influenza vaccine adjuvants.Methods Four kinds of electric charge-modified liposomes were prepared with soybean lecithin,cholesterol,N-1-(2,3-dioleyloxy) propyl-N,N,N-trimethyllam-moniumchloride(DOTAP)and 1,2-dioleoyl-sn-glycero-3-phosphocholine(DOPC)(DOTAP and DOPC mass ratio 1:4,2:3,3:2 and 4:1).The tetravalent influenza vaccine was mixed with the four liposomes according to the volume fraction of 1.4:1.0,which was prepared into cationic modified influenza vaccine liposome freeze-dried powder by freeze-thaw freeze-drying method.The liposome freeze-dried powder was redissolved with PBS,the particle size and Zeta potential were measured by laserparticle size analyzer,and the encapsulation efficiency of liposome was measured by Lowry method.231 female KM mice were randomly divided into negative control group(PBS),positive control group(tetravalent vaccine bulk),cationic liposome group(four electric charge modified influenza vaccine liposomes) and neutral liposome group(non-electric charge modified influenza vaccine liposomes),which were injected intraperitoneally at 7,14 and 28 d,0.2 mL per mouse.The cellular immune effect was evaluated by MTT assay and T lymphatic surface labeling,and the humoral immune effect was evaluated by hemagglutinin inhibition(HI) at 3,7,14,28,42 and 56 d of immunization.Results When the mass ratio of DOTAP to DOPC was 4:1,the particle size and Zeta potential of cationic modified liposomes reached the maximum,which were 529.65 nm and 12.05 mV respectively,and the encapsulation efficiency was also high,which was 81.82%.Stimulus index(SI) and CD4~+/CD8~+value of spleen cells of mice in the four cationic liposome groups were significantly higher than those in the negative control group(F=4.651~25.866,each P<0.05),among which,the two indexes in 4:1 cationic liposome group were higher than those in the other three groups;mice in this group produced early humoral immune effect 3 d after immunization,and the antibody titer reached the highest 42 d after immunization and maintained a high level during the whole immunization cycle.Conclusion Cationic liposomes with different electric charge modifications improved the immune effect of influenza vaccine,the immune enhancement effect was the best and the immune effect lasted the longest when the mass ratio of DOTAP to DOPC was 4:1.

3.
Journal of Pharmaceutical Practice ; (6): 14-17, 2023.
Article in Chinese | WPRIM | ID: wpr-953752

ABSTRACT

Reactive oxygen species(ROS) responsive liposomes are prepared based on the high level of ROS expression in the tumor microenvironment, enabling precise drug delivery to the tumor site. With the addition of photosensitizer, the controllability of drugs in liposomes can be further enhanced.

4.
Acta Pharmaceutica Sinica B ; (6): 3817-3833, 2023.
Article in English | WPRIM | ID: wpr-1011140

ABSTRACT

Chronic inflammation is critical in the onset and progression of atherosclerosis (AS). The lipopolysaccharide (LPS) level in the circulation system is elevated in AS patients and animal models, which is correlated with the severity of AS. Inspired by the underlying mechanism that LPS could drive the polarization of macrophages toward the M1 phenotype, aggravate inflammation, and ultimately contribute to the exacerbation of AS, LPS in the circulation system was supposed to be the therapeutic target for AS treatment. In the present study, polymyxin (PMB) covalently conjugated to PEGylated liposomes (PLPs) were formulated to adsorb LPS through specific interactions between PMB and LPS. In vitro, the experiments demonstrated that PLPs could adsorb LPS, reduce the polarization of macrophages to M1 phenotype and inhibit the formation of foam cells. In vivo, the study revealed that PLPs treatment reduced the serum levels of LPS and pro-inflammatory cytokines, decreased the proportion of M1-type macrophages in AS plaque, stabilized AS plaque, and downsized the plaque burdens in arteries, which eventually attenuated the progression of AS. Our study highlighted LPS in the circulation system as the therapeutic target for AS and provided an alternative strategy for AS treatment.

5.
Acta Pharmaceutica Sinica B ; (6): 3277-3299, 2023.
Article in English | WPRIM | ID: wpr-1011131

ABSTRACT

In recent years, owing to the miniaturization of the fluidic environment, microfluidic technology offers unique opportunities for the implementation of nano drug delivery systems (NDDSs) production processes. Compared with traditional methods, microfluidics improves the controllability and uniformity of NDDSs. The fast mixing and laminar flow properties achieved in the microchannels can tune the physicochemical properties of NDDSs, including particle size, distribution and morphology, resulting in narrow particle size distribution and high drug-loading capacity. The success of lipid nanoparticles encapsulated mRNA vaccines against coronavirus disease 2019 by microfluidics also confirmed its feasibility for scaling up the preparation of NDDSs via parallelization or numbering-up. In this review, we provide a comprehensive summary of microfluidics-based NDDSs, including the fundamentals of microfluidics, microfluidic synthesis of NDDSs, and their industrialization. The challenges of microfluidics-based NDDSs in the current status and the prospects for future development are also discussed. We believe that this review will provide good guidance for microfluidics-based NDDSs.

6.
Acta Pharmaceutica Sinica B ; (6): 3503-3517, 2023.
Article in English | WPRIM | ID: wpr-1011128

ABSTRACT

The use of checkpoint-blockade antibodies is still restricted in several malignancies due to the modest efficacy, despite considerable success in anti-tumor immunotherapy. The poor response of cancer cells to immune destruction is an essential contributor to the failure of checkpoint therapy. We hypothesized that combining checkpoint therapy with natural-product chemosensitizer could enhance immune response. Herein, a targeted diterpenoid derivative was integrated with the checkpoint blockade (anti-CTLA-4) to improve immunotherapy using thermosensitive liposomes as carriers. In vivo, the liposomes enabled the co-delivery of the two drug payloads into the tumor. Consequently, the regulatory T cell proliferation was restrained, the cytotoxic T cell infiltration was enhanced, and the profound immunotherapeutic effect was achieved. In addition, the immunotherapeutic effect of another clinically used checkpoint antibody, anti-PD-1, also benefited from the diterpenoid derivative. Of note, our mechanism study revealed that the targeted diterpenoid derivative increased the sensitivity of cancer cells to immune attack via THBS1 downregulation and the resultant destruction of THBS1-CD47 interaction. Collectively, co-delivering THBS1 inhibitor and checkpoint blockade is promising to boost cancer immunotherapy. We first time discovered that THBS1 suppression could strengthen checkpoint therapy.

7.
Acta Pharmaceutica Sinica B ; (6): 425-439, 2023.
Article in English | WPRIM | ID: wpr-971701

ABSTRACT

Immunoscenescence plays a key role in the initiation and development of tumors. Furthermore, immunoscenescence also impacts drug delivery and cancer therapeutic efficacy. To reduce the impact of immunosenescence on anti-tumor therapy, this experimental plan aimed to use neutrophils with tumor tropism properties to deliver sialic acid (SA)-modified liposomes into the tumor, kill tumor cells via SA-mediated photochemotherapy, enhance infiltration of neutrophils into the tumor, induce immunogenic death of tumor cells with chemotherapy, enhance infiltration of CD8+ T cells into the tumor-draining lymph nodes and tumors of immunosenescent mice, and achieve SA-mediated photochemotherapy. We found that CD8+ T cell and neutrophil levels in 16-month-old mice were significantly lower than those in 2- and 8-month-old mice; 16-month-old mice exhibited immunosenescence. The anti-tumor efficacy of SA-mediated non-photochemotherapy declined in 16-month-old mice, and tumors recurred after scabbing. SA-mediated photochemotherapy enhanced tumor infiltration by CD8+ T cells and neutrophils, induced crusting and regression of tumors in 8-month-old mice, inhibited metastasis and recurrence of tumors and eliminated the immunosenescence-induced decline in antitumor therapeutic efficacy in 16-month-old mice via the light-heat-chemical-immunity conversion.

8.
Journal of Southern Medical University ; (12): 832-838, 2023.
Article in Chinese | WPRIM | ID: wpr-986995

ABSTRACT

OBJECTIVE@#To prepare vitamin E polyethylene glycol 1000 succinate (TPGS)-modified insulin-loaded liposomes (T-LPs/INS) and evaluate its safety, corneal permeability, ocular surface retention and pharmacokinetics in rabbit eyes.@*METHODS@#The safety of the preparation was investigated in human corneal endothelial cells (HCECs) using CCK8 assay and live/dead cell staining. In the ocular surface retention study, 6 rabbits were randomized into 2 equal groups for application of fluorescein sodium dilution or T-LPs/INS labeled with fluorescein in both eyes, which were photographed under cobalt blue light at different time points. In the cornea penetration test, another 6 rabbits divided into 2 groups for application of Nile red diluent or T-LPs/INS labeled with Nile red in both eyes, after which the corneas were harvested for microscopic observation. In the pharmacokinetic study, 2 groups of rabbits (n=24) were treated with eye drops of T-LPs/INS or insulin, and the aqueous humor and cornea were collected at different time points for measurement of insulin concentrations using enzyme linked immunosorbent assay. DAS2 software was used to analyze the pharmacokinetic parameters.@*RESULTS@#The prepared T-LPs/INS showed good safety in cultured HCECs. Corneal permeability assay and fluorescence tracer ocular surface retention assay demonstrated a significantly higher corneal permeability of T-LPs/INS with a prolonged drug residence in the cornea. In the pharmacokinetic study, insulin concentrations in the cornea at 6, 15, 45, 60, and 120 min (P < 0.01) and in the aqueous humor at 15, 45, 60, and 120 min after dosing were significantly higher in T-LPs/INS group. The changes in insulin concentrations in the cornea and aqueous humor were consistent with a two-compartment model in T-LPs/INS group and with the one-compartment model in the insulin group.@*CONCLUSION@#The prepared T-LPs/INS shows an improved corneal permeability, ocular surface retention capacity and eye tissue concentration of insulin in rabbits.


Subject(s)
Humans , Animals , Rabbits , Insulin , Liposomes , Endothelial Cells , Lipopolysaccharides , Vitamin E , Cornea , Fluorescein
9.
Journal of Sun Yat-sen University(Medical Sciences) ; (6): 801-808, 2023.
Article in Chinese | WPRIM | ID: wpr-988726

ABSTRACT

ObjectiveTo investigate the effects of hydroxycamptothecin liposomes (LHCPT) on myocardial fibrosis in rats with heart failure by regulating the sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P) signaling pathway. MethodsSD rats were divided into control group, model group, hydroxycamptothecin (HCPT) group, LHCPT group, captopril group, and LHCPT+K6PC-5 (SphK1 activator) group, with 12 rats in each group. The heart failure rat models in all groups except the control group were established by intraperitoneal injection of doxorubicin and then the corresponding drugs were given once a day. After four weeks, we applied color Doppler ultrasound to detect left ventricular end systolic diameter (LVESD), left ventricular end diastolic diameter (LVEDD), and left ventricular ejection fraction (LVEF) in rats; HE and Masson staining for myocardial pathological damage and myocardial fibrosis in rats, respectively; ELISA method for the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in rat myocardial tissues; qRT-PCR for the expression of transforming growth factor-β1 (TGF-β1), type I collagen (Collagen I), and type Ⅲ collagen (Collagen Ⅲ) in rat myocardial tissues; Western blot for the expression of SphK1 and S1P proteins in rat myocardial tissues. ResultsCompared with the control group, the model group showed severe myocardial pathological damage and myocardial fibrosis, increased LVESD, LVEDD, levels of TNF-α and IL-6, expression of TGF-β1, Collagen I, Collagen Ⅲ, SphK1, S1P and decreased LVEF (P<0.05). Compared with the model group, the HCPT group, LHCPT group and captopril group showed alleviated myocardial pathological damage and myocardial fibrosis, decreased LVESD, LVEDD, levels of TNF-α and IL-6, expression of TGF-β1, Collagen I, Collagen Ⅲ, SphK1, S1P and increased LVEF (P<0.05). Compared with the LHCPT group, the LHCPT+K6PC-5 group showed aggravated myocardial pathological damage and myocardial fibrosis, increased LVESD, LVEDD, levels of TNF-α and IL-6, expression of TGF-β1, Collagen I, Collagen Ⅲ, SphK1, S1P and decreased LVEF (P<0.05). ConclusionLHCPT may inhibit myocardial fibrosis in heart failure rats by inhibiting the SphK1/S1P signaling pathway.

10.
Braz. j. biol ; 832023.
Article in English | LILACS-Express | LILACS, VETINDEX | ID: biblio-1469199

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.

11.
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
12.
Braz. j. biol ; 83: 1-6, 2023. graf, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1468983

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.


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)
Male , Animals , Mice , Anxiety/drug therapy , Eugenol/administration & dosage , Lactoylglutathione Lyase
13.
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
14.
Asian Pacific Journal of Tropical Medicine ; (12): 7-16, 2022.
Article in Chinese | WPRIM | ID: wpr-951062

ABSTRACT

Liposomes are phospholipid bilayer vesicles, which are biocompatible, biodegradable and nontoxic vehicles suitable for numerous drug and gene delivery applications. In this review, we discuss the prospect of using liposome technology in the development of a vaccine for tuberculosis. Tuberculosis remains an important health problem that requires the development of an effective vaccine, especially since the only approved vaccine for it continues to be the Bacille Calmette-Geurin (BCG) one developed 100 years ago. This review focuses on the different applications of liposomes toward achieving this goal. Numerous liposomal formulations showing prospect in the research stage and in clinical trials are discussed.

15.
Acta Pharmaceutica Sinica B ; (6): 3028-3048, 2022.
Article in English | WPRIM | ID: wpr-939954

ABSTRACT

Compared with traditional drug therapy, nanomedicines exhibit intriguing biological features to increase therapeutic efficiency, reduce toxicity and achieve targeting delivery. This review provides a snapshot of nanomedicines that have been currently launched or in the clinical trials, which manifests a diversified trend in carrier types, applied indications and mechanisms of action. From the perspective of indications, this article presents an overview of the applications of nanomedicines involving the prevention, diagnosis and treatment of various diseases, which include cancer, infections, blood disorders, cardiovascular diseases, immuno-associated diseases and nervous system diseases, etc. Moreover, the review provides some considerations and perspectives in the research and development of nanomedicines to facilitate their translations in clinic.

16.
Journal of Prevention and Treatment for Stomatological Diseases ; (12): 73-76, 2022.
Article in Chinese | WPRIM | ID: wpr-904740

ABSTRACT

@#Periodontitis is a common oral disease that represents one of the main causes of tooth loss in adults. In recent years, the application of nanotechnology has provided a new drug delivery system and innovative therapy for the treatment of periodontitis and opens up new prospects for the regeneration of periodontal tissue. The nanoparticle drug delivery system is composed of degradable carrier materials and drugs. Compared with the traditional film, namely, the fragment and strip-shaped periodontal local drug delivery system, the nanoparticle drug delivery system has the characteristics of biopharmaceuticals and pharmacokinetics. Moreover, it has special advantages, including controlled release of drugs, long-term maintenance of drug concentration, biodegradability and biocompatibility, etc. Antibiotics, protein drugs, such as growth factors, and nucleic acids used for gene delivery or mRNA knockout can be absorbed or dissolved in nanoparticles. Liposomes and polymer nanoparticle delivery systems can target bacteria and specific host cells. Inorganic nanoparticles and nanocrystals have good antibacterial activity that can promote periodontal tissue regeneration and play an important role in bone regeneration and bone repair. Dendrimers have internal hydrophobic and external hydrophilic structures and are good drug carriers for periodontitis.

17.
Acta Pharmaceutica Sinica B ; (6): 924-938, 2022.
Article in English | WPRIM | ID: wpr-929335

ABSTRACT

Although multifarious tumor-targeting modifications of nanoparticulate systems have been attempted in joint efforts by our predecessors, it remains challenging for nanomedicine to traverse physiological barriers involving blood vessels, tissues, and cell barriers to thereafter demonstrate excellent antitumor effects. To further overcome these inherent obstacles, we designed and prepared mycoplasma membrane (MM)-fused liposomes (LPs) with the goal of employing circulating neutrophils with the advantage of inflammatory cytokine-guided autonomous tumor localization to transport nanoparticles. We also utilized in vivo neutrophil activation induced by the liposomal form of the immune activator resiquimod (LPs-R848). Fused LPs preparations retained mycoplasma pathogen characteristics and achieved rapid recognition and endocytosis by activated neutrophils stimulated by LPs-R848. The enhanced neutrophil infiltration in homing of the inflammatory tumor microenvironment allowed more nanoparticles to be delivered into solid tumors. Facilitated by the formation of neutrophil extracellular traps (NETs), podophyllotoxin (POD)-loaded MM-fused LPs (MM-LPs-POD) were concomitantly released from neutrophils and subsequently engulfed by tumor cells during inflammation. MM-LPs-POD displayed superior suppression efficacy of tumor growth and lung metastasis in a 4T1 breast tumor model. Overall, such a strategy of pathogen-mimicking nanoparticles hijacking neutrophils in situ combined with enhanced neutrophil infiltration indeed elevates the potential of chemotherapeutics for tumor targeting therapy.

18.
China Pharmacy ; (12): 848-852, 2022.
Article in Chinese | WPRIM | ID: wpr-923192

ABSTRACT

OBJECTIVE To prepare cinnamaldehyde (CA) loaded liposomes bilayer-modified by bovine serum albumin (BSA)/chitosan (CTS)(BSA/CTS-Lip-CA) in order to improve the sustained-release effect and storage stability of the nanoparticles. METHODS Firstly,cinnamaldehyde loaded liposomes (Lip-CA)and blank liposomes (Lip-Blank)were prepared by thin film dispersion method. Then chitosan modified cinnamaldehyde loaded liposome (CTS-Lip-CA)and BSA/CTS-Lip-CA were obtained by electrostatic adsorption. Finally , the prepared liposomes were characterized , and their in vitro release characteristics and storage stability were investigated. RESULTS The particle size of BSA/CTS-Lip-CA was (177.8±4.0)nm and the Zeta potential was (-15.6±1.5)mV;they were in spherical shape ;FTIR analysis showed that the modification of BSA and CTS had no effect on the internal structure of liposomes. The results of in vitro drug release characteristics showed that the cumulative release of Lip-CA ,CTS-Lip-CA and BSA/CTS-Lip-CA within 10 hours were 82.9%,74.1% and 72.9% respectively. The results of storage stability showed that after 30 days of storage ,the particle sizes of Lip-CA ,CTS-Lip-CA and BSA/ CTS-Lip-CA were (134.2±2.1),(151.7±0.4),(164.8±1.5)nm;the retention rates of model drug CA were 65.4%,82.5% and 90.2% respectively. CONCLUSIONS BSA/CTS-Lip-CA is successfully prepared. It has a certain sustained-release effect and can improve the storage stability of the drug to a certain extent.

19.
Braz. J. Pharm. Sci. (Online) ; 58: e20225, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1420359

ABSTRACT

Abstract A cationic liposomal gene delivery system comprising DOTAP, DOPE, and cholesterol was prepared and optimized. The results showed that the liposome/DNA (LP/DNA) system had spherical morphology, with a particle size of around 150 nm and zeta potential of approximately 30 mV. Cytotoxicity experiments showed that cells treated with all of the liposome carriers- with the exception of LP1-had more than 80% viability even at a weight ratio of 30. The in vitro transfection efficiency was measured using a Promega™ Luciferase Assay System. Of the tested lipoplexes, LP2/DNA showed the highest cell transfection efficiency (at a weight ratio of 10)-which was similar to or slightly lower than that of Lipofectamine® 2000 in HeLa, A549, and SPC-A1 cell lines. After freeze-drying, the cell transfection efficiency decreased slightly (P>0.05). The cell uptake mechanism study showed that LP/DNA lipoplexes mainly entered cells via clathrin-mediated and caveolin-mediated endocytic pathways. The results confirmed that LP2 has potential for use as an effective gene carrier, and provides experimental evidence to support its further development as a safe and effective gene delivery system.

20.
Rev. colomb. ciencias quim. farm ; 50(2): 439-456, mayo-ago. 2021. tab, graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1347333

ABSTRACT

RESUMEN Introducción: Actualmente los péptidos sintéticos se han constituido en una novedosa alternativa para el tratamiento de la piel envejecida. Acetilhexapéptido-3 (Ac-EEMQRR-NH2) ha sido utilizado para inducir reducción de líneas de expresión de manera análoga a la toxina botulínica, pero sin efectos tóxicos. Objetivo: Sintetizar el acetilhexapéptido-3 y desarrollar un sistema liposomal para su encapsulación y favorecer su paso a través de una membrana modelo. Metodología: El péptido fue obtenido mediante síntesis en fase sólida (SFS) empleando la estrategia Fmoc/tBu, fue purificado y plenamente caracterizado. El sistema liposomal con acetilhexapéptido-3 encapsulado fue desarrollado mediante la formación de una emulsión con posterior inversión de fase por evaporación del solvente orgánico. Los sistemas fueron caracterizados en su tamaño, potencial zeta, eficiencia de encapsulación del neuropéptido y de manera preliminar se realizó un estudio de permeabilidad ex vivo. Resultados: Es posible sintetizar péptidos cortos con alto grado de pureza y buen rendimiento, utilizando la metodología de SFS Fmoc/tBu. De acuerdo con la caracterización, el sistema liposomal adelantado sugiere una buena estrategia para la encapsulación del acetilhexapéptido-3 y su potencial aplicación en el desarrollo un novedoso producto cosmecéutico.


SUMMARY Introduction: Currently synthetic peptides have become a novel alternative for the treatment of aging skin. Acetylhexapeptide-3 (Ac-EEMQRR-NH2) has been used to induce reduction of expression lines in a manner analogous to botulinum toxin, but without toxic effects. Aim: To synthesize acetylhexapeptide-3 and to develop a lipo-somal system for its encapsulation and favor its passage through a model membrane. Methodology: The peptide was obtained by solid phase synthesis (SFS) using the Fmoc / tBu strategy, it was purified and fully characterized. The liposomal system with encapsulated acetylhexapeptide-3 was developed by forming an emulsion with subsequent phase inversion by evaporation of the organic solvent. The systems were characterized in their size, zeta potential, neuropeptide encapsulation efficiency and a preliminary ex vivo permeability study was carried out. Results: It is possible to synthesize short peptides with a high degree of purity and good yield, using the SFS Fmoc / tBu methodology. According to the characterization, the advanced liposomal system suggests a good strategy for the encapsulation of acetylhexapeptide-3 and its potential application in the development of a novel cosmeceutical product.


RESUMO Introdução: Atualmente os peptídeos sintéticos têm se tornado uma nova alternativa para o tratamento do envelhecimento cutâneo. O acetilhexapeptídeo-3 (Ac-EEMQR-R-NH2) tem sido usado para induzir a redução das linhas de expressão de maneira análoga à toxina botulínica, mas sem efeitos tóxicos. Objetivo: Sintetizar acetilhe-xapeptídeo-3 e desenvolver um sistema lipossomal para seu encapsulamento e favorecer sua passagem por uma membrana modelo. Metodologia: O peptídeo foi obtido por síntese em fase sólida (SFS) utilizando a estratégia Fmoc / tBu, foi purificado e totalmente caracterizado. O sistema lipossomal com acetilhexapeptídeo-3 encapsulado foi desenvolvido pela formação de uma emulsão com subsequente inversão de fase por evaporação do solvente orgânico. Os sistemas foram caracterizados quanto ao tamanho, potencial zeta, eficiência de encapsulação de neuropeptídeos e um estudo preliminar de permeabilidade ex vivo foi realizado. Resultados: É possível sintetizar peptídeos curtos com alto grau de pureza e bom rendimento, utilizando a metodologia SFS Fmoc / tBu. De acordo com a caracterização, o sistema lipossomal avançado sugere uma boa estratégia para a encapsulação do acetilhexapeptídeo-3 e seu potencial aplicação no desenvolvimento de um novo produto cosmecêutico.

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