RESUMEN
Gout and hyperuricemia are characterized by high uric acid levels, and their treatment involves medications that have adverse effects. In this study, we evaluated oral liposomal formulations with eremantholide C and goyazensolide as a novel approach to reduce the toxicity associated with these substances while maintaining their anti-hyperuricemic activity. We characterized the formulations and evaluated them based on encapsulation efficiency and stability over 12 months and under simulated physiological environments. We determined the toxicity of the liposomal formulations in Caco-2 cells and the anti-hyperuricemic activity in rats. The formulations exhibited nanometric size, a narrow size distribution, and a negative zeta potential, indicating their stability and uniformity. The efficient encapsulation of the sesquiterpene lactones within the liposomes emphasizes their potential for sustained release and therapeutic efficacy. Stability evaluation revealed a small decrease in the eremantholide C concentration and a remarkable stability in the goyazensolide concentration. In Caco-2 cells, the liposomes did not exert toxicity, but did exhibit an antiproliferative effect. In vivo assays demonstrated that the liposomes reduced serum uric acid levels. Our study represents an advancement in gout and hyperuricemia treatment. The liposomal formulations effectively reduced the toxicity associated with the sesquiterpene lactones while maintaining their therapeutic effects.
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Artritis Gotosa , Hidrocarburos Aromáticos con Puentes , Furanos , Gota , Hiperuricemia , Sesquiterpenos , Sesterterpenos , Humanos , Ratas , Animales , Liposomas/uso terapéutico , Ácido Úrico/uso terapéutico , Hiperuricemia/tratamiento farmacológico , Células CACO-2 , Gota/tratamiento farmacológico , Lactonas/farmacología , Lactonas/uso terapéuticoRESUMEN
In recent years, nanocarriers have played an ever-increasing role in clinical and biomedical applications owing to their unique physicochemical properties and surface functionalities. Lately, much effort has been directed towards the development of smart, stimuli-responsive nanocarriers that are capable of releasing their cargos in response to specific stimuli. These intelligent-responsive nanocarriers can be further surface-functionalized so as to achieve active tumor targeting in a sequential manner, which can be simply modulated by the stimuli. By applying this methodological approach, these intelligent-responsive nanocarriers can be directed to different target-specific organs, tissues, or cells and exhibit on-demand controlled drug release that may enhance therapeutic effectiveness and reduce systemic toxicity. Light, an external stimulus, is one of the most promising triggers for use in nanomedicine to stimulate on-demand drug release from nanocarriers. Light-triggered drug release can be achieved through light irradiation at different wavelengths, either in the UV, visible, or even NIR region, depending on the photophysical properties of the photo-responsive molecule embedded in the nanocarrier system, the structural characteristics, and the material composition of the nanocarrier system. In this review, we highlighted the emerging functional role of light in nanocarriers, with an emphasis on light-responsive liposomes and dual-targeted stimuli-responsive liposomes. Moreover, we provided the most up-to-date photo-triggered targeting strategies and mechanisms of light-triggered drug release from liposomes and NIR-responsive nanocarriers. Lastly, we addressed the current challenges, advances, and future perspectives for the deployment of light-responsive liposomes in targeted drug delivery and therapy.
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Nanopartículas , Neoplasias , Humanos , Liposomas/uso terapéutico , Portadores de Fármacos/química , Nanopartículas/química , Sistemas de Liberación de Medicamentos , Neoplasias/tratamiento farmacológicoRESUMEN
Tuberculosis is among the infectious diseases with the highest mortality and morbidity worldwide, behind the COVID-19 pandemic. It can affect any organ, although the respiratory infection is the most common. The correct activation of the immune response eliminates or contain the bacteria; however, the active disease is progressive and must be treated under strict supervision. Treatment for tuberculosis is prolonged and consists of a combination of several antibiotics associated with a wide variety of adverse effects. These effects are the main cause of therapeutic abandonment, which facilitates the appearance of drug-resistant strains. Hence the importance of developing new therapeutic strategies to reduce the dose of the drug or its administration time. To achieve these objectives, the use of nano-vehicles, which are controlled and directed drug release systems, has been proposed. Specifically, liposomes are formulations that have advantages when administered by the respiratory route since they facilitate the reach of the respiratory mucosa and the lungs, which are the main organs affected by tuberculosis. This review analyzes the use of nano-vehicles as effective drug delivery systems and the formulations under study. Perspectives for the application of nanotechnology in the development of new pharmacological treatments for tuberculosis are also proposed.
La tuberculosis se ubica entre las enfermedades infecciosas con mayor mortalidad y morbilidad a nivel mundial, por detrás de la actual pandemia de COVID-19. Puede afectar a cualquier órgano, aunque la principal forma de infección es respiratoria. La correcta activación de la respuesta inmune logra eliminar o contener a la bacteria en un estado de latencia; sin embargo, la enfermedad activa es progresiva y debe ser tratada bajo estricta supervisión. El tratamiento para la tuberculosis es prolongado y consiste en una combinación de varios antifímicos; por lo tanto, se asocia a la aparición de una gran diversidad de efectos adversos. Estos efectos son la principal causa de abandono terapéutico, que a su vez facilita la aparición de cepas farmacorresistentes. De ahí la importancia de desarrollar nuevas estrategias terapéuticas con el objetivo de disminuir la dosis del fármaco o bien su tiempo de administración. Para lograr estos objetivos se ha propuesto el uso de nanovehículos, que son sistemas de liberación de fármacos controlados y dirigidos. Específicamente, los liposomas son formulaciones que presentan ventajas al ser administrados por vía respiratoria, ya que esta facilita el alcance a la mucosa respiratoria y a los pulmones, que es el principal órgano afectado en la infección por tuberculosis. En la presente revisión se analiza el uso de nanovehículos como sistemas efectivos de entrega de fármacos, así como las formulaciones que se encuentran en estudio. También se proponen perspectivas para la aplicación de la nanotecnología en el desarrollo de nuevos tratamientos farmacológicos para la tuberculosis.
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COVID-19 , Tuberculosis , Humanos , Liposomas/uso terapéutico , Antituberculosos/uso terapéutico , Antituberculosos/farmacología , Pandemias , Tuberculosis/tratamiento farmacológicoRESUMEN
Aims: The development of rapamycin (RAP) and resveratrol (RSV) coloaded liposomes (RAP-RSV-LIP) for breast cancer therapy. Materials & methods: Liposomes were prepared using a high-pressure homogenization technique and evaluated according to their physicochemical characteristics, cellular uptake and cytotoxicity against tumoral and normal cells. Results & conclusion: The RAP-RSV-LIP showed negative surface charge, size around 100 nm, low polydispersity and high encapsulation efficiency for RAP and RSV (58.87 and 63.22%, respectively). RAP-RSV-LIP showed great stability over 60 days and a prolonged drug-release profile. In vitro studies indicated that RAP-RSV-LIP were internalized in an estrogen receptor-positive human breast cancer cell line (MCF-7, 34.2%) and improved cytotoxicity when compared with free drugs. Therefore RAP-RSV-LIP showed great antitumoral potential against breast cancer cells.
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Neoplasias de la Mama , Liposomas , Humanos , Femenino , Resveratrol/farmacología , Liposomas/uso terapéutico , Sirolimus/farmacología , Sirolimus/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Antioxidantes/uso terapéutico , Línea Celular TumoralRESUMEN
Infectious diseases are the leading cause of death worldwide. Thus, nanotechnology provides an excellent opportunity to treat drug-resistant microbial infections. Numerous antibiotics have been used to inhibit the growth and kill of microbes, but the development of resistance and the emergence of side effects have severely limited the use of these agents. Due to the development of the nanotechnology, nanoparticles are widely used as antimicrobials. Silver and chitosan nanoparticles have antifungal, antiviral and antibacterial properties, and many studies confirm the antifungal properties of silver nanoparticles. Nowadays, the use of nanoparticles in the diagnosis and treatment of infectious diseases has developed due to less side effects and also the help of these particles in effective drug delivery to the target tissue. Liposomes are also used as carriers of drug delivery, genes, and modeling of cell membranes in both animals and humans. The ability of these liposomes to encapsulate large amounts of drugs, minimize unwanted side effects, high effectiveness and low toxicity has attracted the interest of researchers. This review article examines recent efforts by researchers to identify and treat infectious diseases using antimicrobial nanoparticles and drug nano-carriers.
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Enfermedades Transmisibles , Nanopartículas del Metal , Animales , Humanos , Antibacterianos , Antifúngicos , Liposomas/uso terapéutico , Nanopartículas del Metal/uso terapéutico , Plata , Enfermedades Transmisibles/diagnóstico , Enfermedades Transmisibles/tratamiento farmacológicoRESUMEN
In the presence of a vascular thrombus, the recovery of blood flow and vascular recanalization are very important to prevent tissue damage. An alternative procedure to thrombolysis is required for patients who are unable to receive surgery or thrombolytic drugs due to other physical conditions. Recently, the performance of thrombolysis combined with microbubbles has become an attractive and effective therapeutic procedure. Indeed, in a recent study, we demonstrated that, upon exposure to ultrasound, liposomes loaded with nitric oxide release agonists conjugated to microbubbles; therefore, there is potential to release the agonist in a controlled manner into specific tissues. This means that the effect of the agonist is potentiated, decreasing interactions with other tissues, and reducing the dose required to induce nitric-oxide-dependent vasodilation. In the present study, we hypothesized that a liposome microbubble delivery system can be used as a hydrophilic agonist carrier for the nitric oxide donor spermine NONOate, to elicit femoral vasodilation and clot degradation. Therefore, we used spermine-NONOate-loaded microbubbles to evaluate the effect of ultrasound-mediated microbubble disruption (UMMD) on thromboembolic femoral artery recanalization. We prepared spermine NONOate-loaded microbubbles and tested their effect on ex vivo preparations, hypothesizing that ultrasound-induced microbubble disruption is associated with the vasorelaxation of aortic rings. Thrombolysis was demonstrated in aorta blood-flow recovery after disruption by spermine NONOate-loaded microbubbles via ultrasound application in the region where the thrombus is located. Our study provides an option for the clinical translation of NO donors to therapeutic applications.
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Microburbujas , Trombosis , Humanos , Donantes de Óxido Nítrico/farmacología , Donantes de Óxido Nítrico/uso terapéutico , Ultrasonografía , Trombosis/tratamiento farmacológico , Liposomas/uso terapéutico , Óxido Nítrico/farmacologíaRESUMEN
Leishmaniasis is a parasitic disease treatable and curable, however, the chemotherapeutic agents for their treatment are limited. In South American countries, pentavalent antimonials are still the first line of treatment for cutaneous leishmaniasis with an efficacy of about 75%, but the toxicity of the drug causes serious side effects and remains as the main obstacle for treatment. New knowledge aimed to improve drug delivery into the intracellular environment is essential, especially for drugs currently used in the clinic, to develop new anti-Leishmania formulations. In the present study, we analysed the scientific literature to highlight the progress achieved in the last decade regarding the use of nanotechnology for improving the current leishmaniasis treatments. Results allowed us to conclude that the encapsulated Glucantime liposomal formulation can be improved by means of nanoparticle functionalization processes, resulting in new drug delivery systems that can be potentially proposed as alternative therapies for leishmaniasis treatment.
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Antiprotozoarios , Leishmaniasis Cutánea , Leishmaniasis , Nanopartículas , Antiprotozoarios/uso terapéutico , Sistemas de Liberación de Medicamentos , Humanos , Leishmaniasis/tratamiento farmacológico , Leishmaniasis Cutánea/tratamiento farmacológico , Liposomas/uso terapéuticoRESUMEN
BACKGROUND: Leishmaniasis, a still important public health problem, exhibits environmental risk factors such as massive migrations, urbanization, and deforestation. WHO research for Leishmaniasis is mainly focused on the development of new tools, such as diagnostic tests, drugs, and vaccines. During the drug development strategy, only a few compounds were promising and call for further study after the in vitro and in vivo preclinical tests. OBJECTIVE: In this review, our group aimed to highlight the utmost research done during 2014 to 2019 in the fields of natural and synthetic compounds, as well as repurposed drugs and new formulations tested in vivo for Leishmania spp. METHOD: Based on the literature search, we used the databases MEDLINE, PUBMED, CAPES PERIODIC and ELSEVIER to delineate an interval of the last 5 years of research on each field. RESULTS: Among the natural compounds tested, allicin and a fraction of potato tuber extract showed the most promising antileishmanial activity. Concerning synthetic compounds, quinolines, bornyl ester, thymol, benzoxaborole and nitroimidazole derivatives exhibited encouraging results. Moreover, repositioned alternatives involved combinations with known drugs and monotherapy protocols as well. In these years, new formulations were widely assessed as drug delivery systems, such as nanoparticles, micelles and liposomes in polymer conjugations. CONCLUSION: Drug repurposing and new formulations of already-known drugs are worthwhile approaches to promptly introduce new treatment schemes to Leishmaniasis. Nevertheless, the interest in new synthetic compounds and new formulations brings light to new treatment proposals and are notable lines of research.
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Antiprotozoarios , Leishmania , Leishmaniasis , Antiprotozoarios/farmacología , Antiprotozoarios/uso terapéutico , Sistemas de Liberación de Medicamentos , Humanos , Leishmaniasis/tratamiento farmacológico , Liposomas/uso terapéuticoRESUMEN
The treatment of dogs naturally infected with Leishmania infantum using meglumine antimoniate (MA) encapsulated in conventional liposomes (LC) in association with allopurinol has been previously reported to promote a marked reduction in the parasite burden in the main infection sites. Here, a new assay in naturally infected dogs was performed using a novel liposome formulation of MA consisting of a mixture of conventional and long-circulating (PEGylated) liposomes (LCP), with expected broader distribution among affected tissues of the mononuclear phagocyte system. Experimental groups of naturally infected dogs were as follows: LCP plus Allop, receiving LCP intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg of body weight/dose) at 4-day intervals plus allopurinol at 30 mg/kg/12 h per os (p.o.) during 130 days (LCP+Allop); LC plus Allop, receiving LC intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg/dose) plus allopurinol during 130 days (LC+Allop); Allop, treated with allopurinol only; and a nontreated control. Parasite loads were evaluated by quantitative PCR in liver, spleen, and bone marrow tissue and by immunohistochemistry in the ear skin, before treatment, just after treatment, and 4 months later. The LCP+Allop and LC+Allop groups, but not the Allop group, showed significant suppression of the parasites in the liver, spleen, and bone marrow 4 months after treatment compared to the pretreatment period or the control group. Only LCP+Allop group showed significantly lower parasite burden in the skin in comparison to the control group. On the basis of clinical staging and parasitological evaluations, the LCP formulation exhibited a more favorable therapeutic profile than the LC one, being therefore promising for the treatment of canine visceral leishmaniasis.
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Antiprotozoarios , Enfermedades de los Perros , Leishmania infantum , Leishmaniasis Visceral , Compuestos Organometálicos , Alopurinol/uso terapéutico , Animales , Antiprotozoarios/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Perros , Leishmaniasis Visceral/tratamiento farmacológico , Leishmaniasis Visceral/veterinaria , Liposomas/uso terapéutico , Meglumina/uso terapéutico , Antimoniato de Meglumina/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Polietilenglicoles/uso terapéuticoRESUMEN
BACKGROUND: Cancer is characterized by abnormal cell growth and considered one of the leading causes of death around the world. Pharmaceutical Nanotechnology has been extensively studied for the optimization of cancer treatment. OBJECTIVE: Comprehend the panorama of Pharmaceutical Nanotechnology in cancer treatment, through a survey about nanomedicines applied in clinical studies, approved for use and patented. METHODS: Acknowledged products under clinical study and nanomedicines commercialized found in scientific articles through research on the following databases: Pubmed, Science Direct, Scielo and Lilacs. Derwent tool was used for patent research. RESULTS: Nanomedicines based on nanoparticles, polymer micelles, liposomes, dendrimers and nanoemulsions were studied, along with cancer therapies such as Photodynamic Therapy, Infrared Phototherapy Hyperthermia, Magnetic Hyperthermia, Radiotherapy, Gene Therapy and Nanoimmunotherapy. Great advancement has been observed over nanotechnology applied to cancer treatment, mainly for nanoparticles and liposomes. CONCLUSION: The combination of drugs in nanosystems helps to increase efficacy and decrease toxicity. Based on the results encountered, nanoparticles and liposomes were the most commonly used nanocarriers for drug encapsulation. In addition, although few nanomedicines are commercially available, this specific research field is continuously growing.
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Nanopartículas , Neoplasias , Sistemas de Liberación de Medicamentos , Humanos , Liposomas/uso terapéutico , Micelas , Nanomedicina , Nanotecnología , Neoplasias/tratamiento farmacológicoRESUMEN
BACKGROUND: Cancer is a set of diseases formed by abnormal growth of cells leading to the formation of the tumor. The diagnosis can be made through symptoms' evaluation or imaging tests, however, the techniques are limited and the tumor detection may be late. Thus, pharmaceutical nanotechnology has emerged to optimize the cancer diagnosis through nanostructured contrast agent's development. OBJECTIVE: This review aims to identify commercialized nanomedicines and patents for cancer diagnosis. METHODS: The databases used for scientific articles research were Pubmed, Science Direct, Scielo and Lilacs. Research on companies' websites and articles for the recognition of commercial nanomedicines was performed. The Derwent tool was applied for patent research. RESULTS: This article aimed to research on nanosystems based on nanoparticles, dendrimers, liposomes, composites and quantum dots, associated to imaging techniques. Commercialized products based on metal and composite nanoparticles, associated with magnetic resonance and computed tomography, have been observed. The research conducted through Derwent tool displayed a small number of patents using nanotechnology for cancer diagnosis. Among these patents, the most significant number was related to the use of systems based on metal nanoparticles, composites and quantum dots. CONCLUSION: Although few systems are found in the market and patented, nanotechnology appears as a promising field for the development of new nanosystems in order to optimize and accelerate the cancer diagnosis.
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Nanopartículas , Nanoestructuras , Neoplasias , Sistemas de Liberación de Medicamentos , Humanos , Liposomas/uso terapéutico , Nanomedicina/métodos , Nanotecnología , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológicoRESUMEN
Purpose: To assess visual results, macular modifications, and the incidence of clinically significant macular edema (CSME) in patients using a topical triamcinolone acetonide-loaded liposomal formulation (TA-LF) after femtosecond laser-assisted cataract surgery (FLACS). Methods: Fifty-six eyes after FLACS were selected. Twenty-eight eyes in the combined therapy group (P + N) were treated with prednisolone 1% and nepafenac 0.1% for 21 days postoperatively, whereas 28 eyes in the TA-LF group received a liposomal formulation containing 2 mg/mL of TA (0.2%) for the same period of time. Follow-up visits at 1 day, 6 weeks, and 12 weeks after surgery consisted of visual acuity, contrast sensitivity (CS), central foveal thickness (CFT), total macular volume (TMV) measurements, and the detection of CSME. Results: CS improved in the TA-LF group (basal value: 1.087 ± 0.339 vs. 1.276 ± 0.147 at week 12, P = 0.0346), whereas in the P + N group, CS was not different from the baseline (basal value: 1.130 ± 0.331 vs. 1.274 ± 0.133 at week 12, P = 0.1276). There were similar increases in postoperative CFT and TMV in both groups. CFT and TMV significantly correlate with CS only in the TA-LF group. The r2 for CFT and CS was 0.1963 (P = 0.0206), whereas the r2 for TMV and CS was 0.3615 (P = 0.0007) at 12 weeks. No difference was observed in the incidence of CSME between the groups. Conclusion: TA-LF is associated with better CS outcomes compared to combined therapy after FLACS.
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Extracción de Catarata , Cirugía Laser de Córnea , Edema Macular , Triamcinolona Acetonida/uso terapéutico , Administración Tópica , Sensibilidad de Contraste , Composición de Medicamentos , Femenino , Humanos , Liposomas/administración & dosificación , Liposomas/uso terapéutico , Edema Macular/tratamiento farmacológico , Edema Macular/cirugía , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Triamcinolona Acetonida/administración & dosificaciónRESUMEN
Stroke is one of the leading causes of mortality and morbidity worldwide. Due to its poor prognosis, there is a major negative impact on the patients and their family's life quality. However, despite the severity of this pathology tissue plasminogen activator (tPA) is the only FDA approved treatment for ischemic stroke. Moreover, there is no effective treatment for hemorrhagic stroke and only some palliative procedures are often performed to improve the patient's quality of life. Considering this, nanotechnology can offer some advantages for the development of new therapies for stroke. Among the various types of nanomaterials, liposomes are the most extensively studied due to their biocompatibility, biodegradability, and low toxicity. Liposomes, as a drug delivery system, are able to mask therapeutic compounds and allow their passage through the blood-brain barrier. Liposomes also protect drugs from degradation in a biological environment, increasing the circulation time and accumulation in the target tissue. Hence, this review highlights the potential of liposomes applications for delivery of therapeutic compounds for treating stroke.
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Sistemas de Liberación de Medicamentos/métodos , Liposomas/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Animales , Barrera Hematoencefálica/efectos de los fármacos , Isquemia Encefálica/tratamiento farmacológico , Modelos Animales de Enfermedad , Humanos , Liposomas/metabolismo , Calidad de Vida , Activador de Tejido Plasminógeno/farmacologíaAsunto(s)
Portadores de Fármacos/química , Liposomas/uso terapéutico , Sarcoma de Kaposi/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Composición de Medicamentos/métodos , Liberación de Fármacos , Humanos , Liposomas/química , Terapia Molecular Dirigida/métodos , Nanomedicina/métodosRESUMEN
The cutaneous route is attractive for the delivery of drugs in the treatment of a wide variety of diseases. However the stratum corneum (SC) is an effective barrier that hampers skin penetration. Within this context, liposomes emerge as a potential carrier for improving topical delivery of therapeutic agents. In this review, we aimed to discuss key aspects for the topical delivery by drug-loaded liposomes. Phospholipid type and phase transition temperature have been shown to affect liposomal topical delivery. The effect of surface charge is subject to considerable variation depending on drug and composition. In addition, modified vesicles with the presence of components for permeation enhancement, such as surfactants and solvents, have been shown to have a considerable effect. These liposomes include: Transfersomes, Niosomes, Ethosomes, Transethosomes, Invasomes, coated liposomes, penetration enhancer containing vesicles (PEVs), fatty acids vesicles, Archaeosomes and Marinosomes. Furthermore, adding polymeric coating onto liposome surface could influence cutaneous delivery. Mechanisms of delivery include intact vesicular skin penetration, free drug diffusion, permeation enhancement, vesicle adsorption to and/or fusion with the SC, trans-appendageal penetration, among others. Finally, several skin conditions, including acne, melasma, skin aging, fungal infections and skin cancer, have benefited from liposomal topical delivery of drugs, with promising in vitro and in vivo results. However, despite the existence of some clinical trials, more studies are needed to be conducted in order to explore the potential of liposomes in the dermatological field.
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Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/uso terapéutico , Liposomas/administración & dosificación , Liposomas/uso terapéutico , Enfermedades de la Piel/tratamiento farmacológico , Administración Cutánea , Animales , Portadores de Fármacos/síntesis química , Portadores de Fármacos/química , Humanos , Liposomas/síntesis química , Liposomas/químicaRESUMEN
This study aimed to evaluate the in vivo anti-Leishmania amazonensis activity of a Phospholipase A2 (Asp49-PLA2), isolated from Bothrops jararacussu venom, encapsulated in liposomes as a modified toxin release system. The activity of the liposomes was evaluated in BALB/c mice, previously infected with 1×105 of the parasite's promastigotes. The size of the paw lesion in Asp49-PLA2-liposomal-treated animals, after 21days, was observed as decreasing by 16% relative to the untreated control group and 12% by the Glucantime®-treated animals, which was used as a reference drug. At the end of the treatment, the animals were sacrificed and the paw and lymph node tissues were collected. Part of the collection was used to recover amastigotes and another to quantify cytokines and nitrites. In the group treated with Asp49-PLA2-liposomes the parasitic load was observed to be reduced by 73.5% in the macerated lymph node, compared to the control group. Comparatively, in the paw tissue was observed a reduction of 57.1%. The infected groups treated with Asp49-PLA2-liposomes showed significant production in TNF-α measured in lymph nodes and paw (43.73pg/mL±2.25 and 81.03pg/mL±5.52, respectively) and nitrite levels (31.28µM±0.58 and 35.64µM±5.08) also measured in lymph nodes and paw tissues, respectively, compared to untreated groups. These results indicate that the Asp49-PLA2-loaded liposomes were able to activate the production of some cellular components of the protective TH1 response during the infection, constituting a promising tool for inducing the microbicidal activity of the Leishmania-infected macrophages.
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Venenos de Crotálidos/metabolismo , Leishmania/fisiología , Leishmaniasis Cutánea/terapia , Liposomas/metabolismo , Ganglios Linfáticos/inmunología , Macrófagos/inmunología , Fosfolipasas A2/metabolismo , Proteínas de Reptiles/metabolismo , Animales , Antiinfecciosos/metabolismo , Bothrops , Modelos Animales de Enfermedad , Humanos , Liposomas/uso terapéutico , Ganglios Linfáticos/parasitología , Macrófagos/parasitología , Masculino , Ratones , Ratones Endogámicos BALB C , Nitritos/metabolismo , Carga de Parásitos , Fosfolipasas A2/uso terapéutico , Proteínas de Reptiles/uso terapéutico , Células TH1/inmunología , Terapias en Investigación , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Pentavalent antimonial has been the first choice treatment for visceral leishmaniasis; however, it has several side effects that leads to low adherence to treatment. Liposome-encapsulated meglumine antimoniate (MA) arises as an important strategy for chemotherapy enhancement. We evaluated the immunopathological changes using the mixture of conventional and pegylated liposomes with MA. The mice were infected with Leishmania infantum and a single-dose treatment regimen. Comparison was made with groups treated with saline, empty liposomes, free MA, and a liposomal formulation of MA (Lipo MA). Histopathological analyses demonstrated that animals treated with Lipo MA showed a significant decrease in the inflammatory process and the absence of granulomas. The in vitro stimulation of splenocytes showed a significant increase of gamma interferon (IFN-γ) produced by CD8+ T cells and a decrease in interleukin-10 (IL-10) produced by CD4+ and CD8+ T cells in the Lipo MA. Furthermore, the Lipo MA group showed an increase in the IFN-γ/IL-10 ratio in both CD4+ and CD8+ T cell subsets. According to the parasite load evaluation using quantitative PCR, the Lipo MA group showed no L. infantum DNA in the spleen (0.0%) and 41.4% in the liver. In addition, we detected a low positive correlation between parasitism and histopathology findings (inflammatory process and granuloma formation). Thus, our results confirmed that Lipo MA is a promising antileishmanial formulation able to reduce the inflammatory response and induce a type 1 immune response, accompanied by a significant reduction of the parasite burden into hepatic and splenic compartments in treated animals.
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Antiprotozoarios/uso terapéutico , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Leishmania infantum/efectos de los fármacos , Leishmaniasis Visceral/tratamiento farmacológico , Meglumina/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Animales , Sistemas de Liberación de Medicamentos , Femenino , Inflamación/prevención & control , Interferón gamma/inmunología , Interleucina-10/biosíntesis , Leishmaniasis Visceral/parasitología , Liposomas/uso terapéutico , Meglumina/química , Antimoniato de Meglumina , Ratones , Ratones Endogámicos BALB C , Compuestos Organometálicos/química , Carga de Parásitos , Polietilenglicoles/químicaRESUMEN
The current work was conducted to verify the contribution of neuromuscular transmission defects at the neuromuscular junction to Duchenne Muscular Dystrophy disease progression and respiratory dysfunction. We tested pyridostigmine and pyridostigmine encapsulated in liposomes (liposomal PYR), an acetylcholinesterase inhibitor to improve muscular contraction on respiratory muscle function in mdx mice at different ages. We evaluated in vivo with the whole-body plethysmography, the ventilatory response to hypercapnia, and measured in vitro diaphragm strength in each group. Compared to C57BL10 mice, only 17 and 22 month-old mdx presented blunted ventilatory response, under normocapnia and hypercapnia. Free pyridostigmine (1mg/kg) was toxic to mdx mice, unlike liposomal PYR, which did not show any side effect, confirming that the encapsulation in liposomes is effective in reducing the toxic effects of this drug. Treatment with liposomal PYR, either acute or chronic, did not show any beneficial effect on respiratory function of this DMD experimental model. The encapsulation in liposomes is effective to abolish toxic effects of drugs.
Asunto(s)
Inhibidores de la Colinesterasa/farmacología , Distrofia Muscular de Duchenne/complicaciones , Bromuro de Piridostigmina/farmacología , Trastornos Respiratorios , Músculos Respiratorios/efectos de los fármacos , Factores de Edad , Animales , Inhibidores de la Colinesterasa/uso terapéutico , Modelos Animales de Enfermedad , Sistemas de Liberación de Medicamentos , Técnicas In Vitro , Liposomas/uso terapéutico , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos mdx , Contracción Muscular/efectos de los fármacos , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/patología , Pletismografía , Bromuro de Piridostigmina/uso terapéutico , Trastornos Respiratorios/tratamiento farmacológico , Trastornos Respiratorios/etiología , Trastornos Respiratorios/patología , Frecuencia Respiratoria/efectos de los fármacos , Espectrofotometría Ultravioleta , Volumen de Ventilación Pulmonar/efectos de los fármacosRESUMEN
The study of neglected diseases has not received much attention, especially from public and private institutions over the last years, in terms of strong support for developing treatment for these diseases. Support in the form of substantial amounts of private and public investment is greatly needed in this area. Due to the lack of novel drugs for these diseases, nanobiotechnology has appeared as an important new breakthrough for the treatment of neglected diseases. Recently, very few reviews focusing on filiarasis, leishmaniasis, leprosy, malaria, onchocerciasis, schistosomiasis, trypanosomiasis, and tuberculosis, and dengue virus have been published. New developments in nanocarriers have made promising advances in the treatment of several kinds of diseases with less toxicity, high efficacy and improved bioavailability of drugs with extended release and fewer applications. This review deals with the current status of nanobiotechnology in the treatment of neglected diseases and highlights how it provides key tools for exploring new perspectives in the treatment of a wide range of diseases.
Asunto(s)
Portadores de Fármacos/uso terapéutico , Nanopartículas/uso terapéutico , Enfermedades Desatendidas/tratamiento farmacológico , Medicina Tropical , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/efectos adversos , Portadores de Fármacos/farmacocinética , Humanos , Leishmaniasis/tratamiento farmacológico , Lepra/tratamiento farmacológico , Liposomas/farmacocinética , Liposomas/uso terapéutico , Malaria/tratamiento farmacológico , Nanopartículas/administración & dosificación , Nanopartículas/efectos adversos , Oncocercosis/tratamiento farmacológico , Esquistosomiasis/tratamiento farmacológico , Tripanosomiasis/tratamiento farmacológico , Tuberculosis/tratamiento farmacológicoRESUMEN
Invasive mycoses are a major problem for immunocompromised individuals and patients in intensive care units. Morbidity and mortality rates of these infections are high because of late diagnosis and delayed treatment. Moreover, the number of available antifungal agents is low, and there are problems with toxicity and resistance. Alternatives for treating invasive fungal infections are necessary. Nanostructured systems could be excellent carriers for antifungal drugs, reducing toxicity and targeting their action. The use of nanostructured systems for antifungal therapy began in the 1990s, with the appearance of lipid formulations of amphotericin B. This review encompasses different antifungal drug delivery systems, such as liposomes, carriers based on solid lipids and nanostructure lipids, polymeric nanoparticles, dendrimers, and others. All these delivery systems have advantages and disadvantages. Main advantages are the improvement in the antifungal properties, such as bioavailability, reduction in toxicity, and target tissue, which facilitates innovative therapeutic techniques. Conversely, a major disadvantage is the high cost of production. In the near future, the use of nanosystems for drug delivery strategies can be used for delivering peptides, including mucoadhesive systems for the treatment of oral and vaginal candidiasis.