Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 130
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Pharm Dev Technol ; 29(1): 25-39, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38014878

RESUMEN

BACKGROUND: Emulgels, hybrid formulations of emulsions and gels, offer distinct benefits viz. extended release, enhanced bioavailability, and targeted drug delivery to inflamed joints, thereby minimizing systemic side effects, and maximizing therapeutic efficacy in targeting the diseases. Oral medications and topical creams have limitations viz. limited permeation, efficacy, and side effects. Arthritis is a prevalent chronic inflammatory disorder affecting a substantial global population of about 350 million necessitating the exploration of innovative and effective treatment approaches. Inflammation of one or more joints in the body is referred to generally as arthritis, associated with joint discomfort, edema, stiffness, and decreased motion in the joints. MAIN PART: Emulgels further improve drug solubility and penetration into the affected tissues, augmenting the potential for disease-modifying effects. This review article comprehensively examines recent research for the potential of emulgels (micro- and nanoemulgels) as a potential therapeutic approach for arthritis management, thus showcasing their promising potential in precise treatment regimens. Despite the considerable progress in emulgel-based arthritis therapies, the review emphasizes the need for additional research and translation to clinical trials, thus ascertaining their long-term safety, efficacy, and cost-effectiveness compared to conventional treatments. CONCLUSION: With ongoing advancements in drug delivery, emulgels present an exciting frontier in arthritis-associated conditions, with the potential to revolutionize arthritis treatment and significantly enhance patient life's quality.


Asunto(s)
Artritis , Sistemas de Liberación de Medicamentos , Humanos , Artritis/tratamiento farmacológico , Geles
2.
AAPS PharmSciTech ; 25(5): 96, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38710855

RESUMEN

Central nervous system-related disorders have become a continuing threat to human life and the current statistic indicates an increasing trend of such disorders worldwide. The primary therapeutic challenge, despite the availability of therapies for these disorders, is to sustain the drug's effective concentration in the brain while limiting its accumulation in non-targeted areas. This is attributed to the presence of the blood-brain barrier and first-pass metabolism which limits the transportation of drugs to the brain irrespective of popular and conventional routes of drug administration. Therefore, there is a demand to practice alternative routes for predictable drug delivery using advanced drug delivery carriers to overcome the said obstacles. Recent research attracted attention to intranasal-to-brain drug delivery for promising targeting therapeutics in the brain. This review emphasizes the mechanisms to deliver therapeutics via different pathways for nose-to-brain drug delivery with recent advancements in delivery and formulation aspects. Concurrently, for the benefit of future studies, the difficulties in administering medications by intranasal pathway have also been highlighted.


Asunto(s)
Administración Intranasal , Encéfalo , Sistemas de Liberación de Medicamentos , Animales , Humanos , Administración Intranasal/métodos , Barrera Hematoencefálica/metabolismo , Encéfalo/metabolismo , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Mucosa Nasal/metabolismo , Preparaciones Farmacéuticas/administración & dosificación
3.
Small ; 19(8): e2205819, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36564365

RESUMEN

Immunogenic carrier proteins such as the non-toxic diphtheria toxin variant, cross-reacting material 197 (CRM197), are widely used in subunit vaccine formulations to boost immunogenicity of chemically conjugated antigens. Conjugate vaccines are inherently expensive due to laborious manufacturing steps. Here, this work develops a particulate vaccine platform based on using engineered Escherichia coli to assemble CRM197-antigen fusion proteins into discrete submicron-sized particles. This approach enables precise loading of diverse antigens and epitopes enhancing their immunogenicity. A cost-effective, high-yield, and scalable biomanufacturing process is developed. Purified particulate CRM197-antigen vaccines are ambient-temperature stable. CRM197 particles incorporating pathogen-specific antigens or epitopes from SARS-CoV-2, Streptococcus pyogenes (group A), and Mycobacterium tuberculosis induced cell-mediated and humoral immune responses mediating protective immunity in respective animal models of infection. The CRM197 particle vaccine platform is versatile, enabling co-delivery of selected antigens/epitopes together with immunogenic CRM197 as discrete stable particles avoiding laborious manufacture of soluble CRM197 and antigen followed by chemical conjugation.


Asunto(s)
COVID-19 , Animales , SARS-CoV-2 , Proteínas Bacterianas/química , Vacunas Sintéticas , Vacunas Conjugadas , Antígenos , Epítopos
4.
J Biochem Mol Toxicol ; 37(11): e23482, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37530602

RESUMEN

Inflammation is an essential immune response that helps fight infections and heal tissues. However, chronic inflammation has been linked to several diseases, including cancer, autoimmune disorders, cardiovascular diseases, and neurological disorders. This has increased interest in finding natural substances that can modulate the immune system inflammatory signaling pathways to prevent or treat these diseases. Luteolin is a flavonoid found in many fruits, vegetables, and herbs. It has been shown to have anti-inflammatory effects by altering signaling pathways in immune cells. This review article discusses the current research on luteolin's role as a natural immune system modulator of inflammatory signaling mechanisms, such as its effects on nuclear factor-kappa B, mitogen-activated protein kinases, Janus kinase/signal transducer and activator of transcription, and inflammasome signaling processes. The safety profile of luteolin and its potential therapeutic uses in conditions linked to inflammation are also discussed. Overall, the data point to Luteolin's intriguing potential as a natural regulator of immune system inflammatory signaling processes. More research is needed to fully understand its mechanisms of action and possible therapeutic applications.


Asunto(s)
Luteolina , Neoplasias , Humanos , Luteolina/farmacología , Luteolina/uso terapéutico , Inflamación/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Transducción de Señal , Sistema Inmunológico
5.
AAPS PharmSciTech ; 24(6): 151, 2023 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-37438613

RESUMEN

Since earlier times, dermatological remedies have been utilized to treat diseases associated with pain, irritation, and skin conditions. Compared to other routes of drug delivery, topical delivery of drugs offers several benefits. Scientists are investigating different alterations in dosage forms in addition to existing topical formulations such as ointments, gels, creams, lotions, and ointments to significantly improve the permeation of drugs and enhance the pharmacological efficacy of medications that are poorly absorbed via the skin. Conventional formulations have a plethora of problems viz. poor absorption, no target specificity, low spreadability, and inadequate bioavailability which leads the researchers toward developing novel formulations like nanoemulsions. The nanoemulsion can enhance the gradient in concentration and thermodynamic movement toward the epidermis and enhance the penetration of its constituents. However, due to its difficult application, nanoemulsion's lower viscosity limited its use in transdermal delivery. Thus, the development of nanoemulsion-based hydrogels has shown to be a successful strategy for removing obstacles from existing drug formulations. The simple application, expedient spreadability, non-stickiness, safety, and effectiveness of nanoemulsion-based hydrogel have led to substantial growth in their research in recent years. This review gives a brief idea about the prevalence of skin diseases, skin as an obstacle for drug delivery, and recent research insights to combat these obstacles. The work highlights the mechanism of drug release via nanoemulsion, hydrogels, and nanoemulsion-based hydrogels with reference to recent research on hydrophobic and hydrophilic drugs.


Asunto(s)
Sistemas de Liberación de Medicamentos , Hidrogeles , Pomadas , Difusión , Disponibilidad Biológica
6.
AAPS PharmSciTech ; 24(8): 252, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-38049695

RESUMEN

Tuberculosis (TB) is among the top 10 infectious diseases worldwide. It is categorized among the leading killer diseases that are the reason for the death of millions of people globally. Although a standardized treatment regimen is available, non-adherence to treatment has increased multi-drug resistance (MDR) and extensive drug-resistant (XDR) TB development. Another challenge is targeting the death of TB reservoirs in the alveoli via conventional treatment. TB Drug resistance may emerge as a futuristic restraint of TB with the scarcity of effective Anti-tubercular drugs. The paradigm change towards nano-targeted drug delivery systems is mostly due to the absence of effective therapy and increased TB infection recurrent episodes with MDR. The emerging field of nanotechnology gave an admirable opportunity to combat MDR and XDR via accurate diagnosis with effective treatment. The new strategies targeting the lung via the pulmonary route may overcome the new incidence of MDR and enhance patient compliance. Therefore, this review highlights the importance and recent research on pulmonary drug delivery with nanotechnology along with prevalence, the need for the development of nanotechnology, beneficial aspects of nanomedicine, safety concerns of nanocarriers, and clinical studies.


Asunto(s)
Tuberculosis Extensivamente Resistente a Drogas , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Antituberculosos/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Tuberculosis Extensivamente Resistente a Drogas/epidemiología , Sistemas de Liberación de Medicamentos , Pulmón
7.
Pharm Res ; 39(6): 1115-1134, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35386012

RESUMEN

Cancer is associated with a comprehensive burden that significantly affects patient's quality of life. Even though patients' disease condition is improving following conventional therapies, researchers are studying alternative tools that can penetrate solid tumours to deliver the therapeutics due to issues of developing resistance by the cancer cells. Treating cancer is not the only the goal in cancer therapy; it also includes protecting non-cancerous cells from the toxic effects of anti-cancer agents. Thus, various advanced techniques, such as cell-based drug delivery, bacteria-mediated therapy, and nanoparticles, are devised for site-specific delivery of drugs. One of the novel methods that can be targeted to deliver anti-cancer agents is by utilising genetically modified non-pathogenic bacterial species. This is due to the ability of bacterial species to multiply selectively or non-selectively on tumour cells, resulting in biofilms that leads to disruption of metastasis process. In preclinical studies, this technology has shown significant results in terms of efficacy, and some are currently under investigation. Therefore, researchers have conducted studies on bacteria transporting the anti-cancer drug to targeted tumours. Alternatively, bacterial ghosts and bacterial spores are utilised to deliver anti-cancer drugs. Although in vivo studies of bacteria-mediated cancer therapy have shown successful outcome, further research on bacteria, specifically their targeting mechanism, is required to establish a complete clinical approach in cancer treatment. This review has focused on the up-to-date understanding of bacteria as a therapeutic carrier in the treatment of cancer as an emerging field.


Asunto(s)
Antineoplásicos , Neoplasias , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Bacterias , Sistemas de Liberación de Medicamentos , Excipientes , Humanos , Neoplasias/patología , Calidad de Vida
8.
Surg Radiol Anat ; 44(1): 83-92, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34994829

RESUMEN

PURPOSE: The physicians say that the least anatomy is required for clinical practice. But the disease causes anatomical distortions or variations in structures impairing functions of organs and systems. So, the diagnosis and analysis of treatment of disease depend on interwoven inter-relationship among Anatomy, Physiology, Pathology, Radiology and clinical sciences. Consequently, the upcoming doctors are to be cultivated sufficient anatomy. Therefore, the objective of this study is to analyze viewpoints of medical students, faculties and practitioners regarding degree of need of Anatomy in clinical practice. METHODS: A feedback survey has been carried out among students and faculties to seek their views on the need of Anatomy in clinical practice using two hypotheses. Hypothesis 1 defines the degree of need of Anatomy ('most essential', 'essential' and 'least essential') in clinical practice based on answers of questionnaire by medical students and faculties, whereas hypothesis 2 assigns weights depending on knowledge and experience of the feedback providers. The means/weighted means of views have been statistically analyzed. Additionally, the literature survey was carried out on the demand, necessity, importance, usefulness and applicability of Anatomy in clinical practice. RESULTS: Our statistical analysis revealed that Anatomy is 'most essential' for clinical practice. In literature survey too, the inadequate knowledge of anatomy among medical students leads to poor comprehension of clinical practice. So, anatomy is most essential for clinical practice. CONCLUSION: Sound knowledge of Human Anatomy is most essential during medical practice for Physicians.


Asunto(s)
Anatomía , Educación de Pregrado en Medicina , Médicos , Radiología , Estudiantes de Medicina , Anatomía/educación , Curriculum , Docentes , Humanos , Encuestas y Cuestionarios
9.
PLoS Comput Biol ; 16(6): e1007182, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32502148

RESUMEN

Group A Streptococcus (GAS) skin infections are caused by a diverse array of strain types and are highly prevalent in disadvantaged populations. The role of strain-specific immunity in preventing GAS infections is poorly understood, representing a critical knowledge gap in vaccine development. A recent GAS murine challenge study showed evidence that sterilising strain-specific and enduring immunity required two skin infections by the same GAS strain within three weeks. This mechanism of developing enduring immunity may be a significant impediment to the accumulation of immunity in populations. We used an agent-based mathematical model of GAS transmission to investigate the epidemiological consequences of enduring strain-specific immunity developing only after two infections with the same strain within a specified interval. Accounting for uncertainty when correlating murine timeframes to humans, we varied this maximum inter-infection interval from 3 to 420 weeks to assess its impact on prevalence and strain diversity, and considered additional scenarios where no maximum inter-infection interval was specified. Model outputs were compared with longitudinal GAS surveillance observations from northern Australia, a region with endemic infection. We also assessed the likely impact of a targeted strain-specific multivalent vaccine in this context. Our model produced patterns of transmission consistent with observations when the maximum inter-infection interval for developing enduring immunity was 19 weeks. Our vaccine analysis suggests that the leading multivalent GAS vaccine may have limited impact on the prevalence of GAS in populations in northern Australia if strain-specific immunity requires repeated episodes of infection. Our results suggest that observed GAS epidemiology from disease endemic settings is consistent with enduring strain-specific immunity being dependent on repeated infections with the same strain, and provide additional motivation for relevant human studies to confirm the human immune response to GAS skin infection.


Asunto(s)
Enfermedades de la Piel/epidemiología , Infecciones Estreptocócicas/epidemiología , Streptococcus pyogenes , Animales , Australia/epidemiología , Australia/etnología , Número Básico de Reproducción , Modelos Animales de Enfermedad , Humanos , Ratones , Modelos Teóricos , Dinámica Poblacional , Grupos de Población , Enfermedades de la Piel/inmunología , Enfermedades de la Piel/microbiología , Enfermedades de la Piel/prevención & control , Infecciones Estreptocócicas/inmunología , Infecciones Estreptocócicas/prevención & control , Vacunas Estreptocócicas
10.
Molecules ; 26(9)2021 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-34062995

RESUMEN

A single ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that causes inflammation of the colonic mucosa at the distal colon and rectum. The mainstay therapy involves anti-inflammatory immunosuppression based on the disease location and severity. The disadvantages of using systemic corticosteroids for UC treatment is the amplified risk of malignancies and infections. Therefore, topical treatments are safer as they have fewer systemic side effects due to less systemic exposure. In this context, pH sensitive and enzymatically triggered hydrogel of pectin (PC) and polyacrylamide (PAM) has been developed to facilitate colon-targeted delivery of budesonide (BUD) for the treatment of UC. The hydrogels were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), swelling ratio, and drug release. FT-IR spectroscopy confirmed the grafting as well loading of BUD in hydrogel. XRD showed the amorphous nature of hydrogel and increment in crystallinity after drug loading. On the other hand, SEM showed that the hydrogels exhibited a highly porous morphology, which is suitable for drug loading and also demonstrated a pH-responsive swelling behaviour, with decreased swelling in acidic media. The in-vitro release of BUD from the hydrogel exhibited a sustained release behaviour with non-ficken diffusion mechanism. The model that fitted best for BUD released was the Higuchi kinetic model. It was concluded that enzyme/pH dual-sensitive hydrogels are an effective colon-targeted delivery system for UC.


Asunto(s)
Resinas Acrílicas/química , Budesonida/farmacología , Liberación de Fármacos , Hidrogeles/química , Pectinas/química , Rastreo Diferencial de Calorimetría , Preparaciones de Acción Retardada , Hidrogeles/síntesis química , Concentración de Iones de Hidrógeno , Cinética , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos X
11.
J Immunol ; 199(8): 2794-2802, 2017 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-28904125

RESUMEN

Peptides offer enormous promise as vaccines to prevent and protect against many infectious and noninfectious diseases. However, to date, limited vaccine efficacy has been reported and none have been licensed for human use. Innovative ways to enhance their immunogenicity are being tested, but rational sequence modification as a means to improve immune responsiveness has been neglected. Our objective was to establish a two-step generic protocol to modify defined amino acids of a helical peptide epitope to create a superior immunogen. Peptide variants of p145, a conserved helical peptide epitope from the M protein of Streptococcus pyogenes, were designed by exchanging one amino acid at a time, without altering their α-helical structure, which is required for correct antigenicity. The immunogenicities of new peptides were assessed in outbred mice. Vaccine efficacy was assessed in a skin challenge and invasive disease model. Out of 86 variants of p145, seven amino acid substitutions were selected and made the basis of the design for 18 new peptides. Of these, 13 were more immunogenic than p145; 7 induced Abs with significantly higher affinity for p145 than Abs induced by p145 itself; and 1 peptide induced more than 10,000-fold greater protection following challenge than the parent peptide. This peptide also only required a single immunization (compared with three immunizations with the parent peptide) to induce complete protection against invasive streptococcal disease. This study defines a strategy to rationally improve the immunogenicity of peptides and will have broad applicability to the development of vaccines for infectious and noninfectious diseases.


Asunto(s)
Antígenos Bacterianos/metabolismo , Proteínas de la Membrana Bacteriana Externa/metabolismo , Proteínas Portadoras/metabolismo , Fragmentos de Péptidos/metabolismo , Infecciones Estreptocócicas/inmunología , Vacunas Estreptocócicas/inmunología , Streptococcus pyogenes/inmunología , Animales , Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/genética , Antígenos Bacterianos/inmunología , Proteínas de la Membrana Bacteriana Externa/genética , Proteínas de la Membrana Bacteriana Externa/inmunología , Proteínas Portadoras/genética , Proteínas Portadoras/inmunología , Humanos , Inmunidad Humoral , Inmunización , Ratones , Ratones Endogámicos BALB C , Mutación/genética , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/inmunología , Ingeniería de Proteínas , Infecciones Estreptocócicas/prevención & control , Vacunas de Subunidad
12.
Drug Dev Ind Pharm ; 45(2): 323-332, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30404554

RESUMEN

Betamethsone valerate (BMV), a medium potency topical corticosteroid, is one of the most commonly employed pharmacological agents for the management of atopic dermatitis in both adults and children. Despite having remarkable pharmacological efficacy, these agents have limited clinical implication due to poor penetration across the startum cornum (SC). To mitigate issues related to targeted delivery, stability, and solubility as well as to potentiate therapeutic and clinical implication, the nanodelivery systems have gained remarkable recognition. Therefore, this study was aimed to encapsulate BMV into the chitosan nanoparticles (CS-NPs) for optimum dermal targeting and improved penetration across the SC. The prepared NPs were characterized for particle size, zeta potential, polydispersity index, entrapment efficiency, loading capacity, crystallinity, thermal behavior, morphology, in vitro release kinetics, drug permeation across the SC, and percentage of drug retained into various skin layers. Results showed that optimized BMV-CS-NPs exhibited optimum physicochemical characteristics including small particle size (< 250 ± 28 nm), higher zeta potential (+58 ± 8 mV), and high entrapment efficiency (86 ± 5.6%) and loading capacity (34 ± 7.2%). The in vitro release study revealed that BMV-CS-NPs displayed Fickian-diffusion type mechanism of release in simulated skin surface (pH 5.5). Drug permeation efficiency and the amount of BMV retained into the epidermis and the dermis were comparatively higher in case of BMV-CS-NPs compared to BMV solution. Conclusively, we anticipated that BMV-CS-NPs could be a promising nanodelivery system for efficient dermal targeting of BMV and improved anti-AD efficacy.


Asunto(s)
Antiinflamatorios/administración & dosificación , Valerato de Betametasona/administración & dosificación , Administración Tópica , Animales , Antiinflamatorios/química , Valerato de Betametasona/química , Quitosano , Dermatitis Atópica/tratamiento farmacológico , Composición de Medicamentos , Sistemas de Liberación de Medicamentos , Tamaño de la Partícula , Presión , Ratas , Ratas Wistar , Piel/efectos de los fármacos , Solventes
13.
PLoS Pathog ; 12(12): e1006122, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28027314

RESUMEN

The immunobiology underlying the slow acquisition of skin immunity to group A streptococci (GAS), is not understood, but attributed to specific virulence factors impeding innate immunity and significant antigenic diversity of the type-specific M-protein, hindering acquired immunity. We used a number of epidemiologically distinct GAS strains to model the development of acquired immunity. We show that infection leads to antibody responses to the serotype-specific determinants on the M-protein and profound protective immunity; however, memory B cells do not develop and immunity is rapidly lost. Furthermore, antibodies do not develop to a conserved M-protein epitope that is able to induce immunity following vaccination. However, if re-infected with the same strain within three weeks, enduring immunity and memory B-cells (MBCs) to type-specific epitopes do develop. Such MBCs can adoptively transfer protection to naïve recipients. Thus, highly protective M-protein-specific MBCs may never develop following a single episode of pyoderma, contributing to the slow acquisition of immunity and to streptococcal endemicity in at-risk populations.


Asunto(s)
Memoria Inmunológica/inmunología , Piodermia/inmunología , Piodermia/microbiología , Infecciones Estreptocócicas/inmunología , Infecciones Estreptocócicas/microbiología , Animales , Ensayo de Inmunoadsorción Enzimática , Ratones , Streptococcus pyogenes
14.
J Immunol ; 196(8): 3364-74, 2016 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-26969753

RESUMEN

Cluster of virulence responder/sensor (CovR/S) mutant group A streptococci (GAS) are serious human pathogens of multiple M protein strains that upregulate expression of virulence factors, including the IL-8 proteaseStreptococcus pyogenescell envelope proteinase (SpyCEP), thus blunting neutrophil-mediated killing and enabling ingress of bacteria from a superficial wound to deep tissue. We previously showed that a combination vaccine incorporating J8-DT (conserved peptide vaccine from the M protein) and a recombinant SpyCEP fragment protects against CovR/S mutants. To enhance the vaccine's safety profile, we identified a minimal epitope (S2) that was the target for anti-SpyCEP Abs that could protect IL-8 from SpyCEP-mediated proteolysis. Abs from healthy humans and from mice experimentally infected with GAS also recognized S2, albeit at low titers. Native SpyCEP may be poorly immunogenic (cryptic or subdominant), and it would be to the organism's advantage if the host did not induce a strong Ab response against it. However, S2 conjugated to diphtheria toxoid is highly immunogenic and induces Abs that recognize and neutralize SpyCEP. Hence, we describe a two-component peptide vaccine that induces Abs (anti-S2) that protect IL-8 from proteolysis and other Abs (anti-J8) that cause strain-independent killing in the presence of neutrophils. We show that either component alone is ineffectual in preventing skin infection and bacteremia due to CovR/S mutants but that the combination induces complete protection. This protection correlated with a significant influx of neutrophils to the infection site. The data strongly suggest that the lack of natural immunity to hypervirulent GAS strains in humans could be rectified by this combination vaccine.


Asunto(s)
Antígenos Bacterianos/inmunología , Proteínas de la Membrana Bacteriana Externa/inmunología , Proteínas Portadoras/inmunología , Péptido Hidrolasas/inmunología , Infecciones Estreptocócicas/inmunología , Vacunas Estreptocócicas/inmunología , Streptococcus pyogenes/inmunología , Animales , Anticuerpos Antibacterianos/inmunología , Bacteriemia/inmunología , Bacteriemia/microbiología , Bacteriemia/prevención & control , Proteínas Bacterianas/inmunología , Toxoide Diftérico/inmunología , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Neutrófilos/inmunología , Péptido Hidrolasas/biosíntesis , Péptido Hidrolasas/genética , Piel/microbiología , Enfermedades Cutáneas Bacterianas/inmunología , Enfermedades Cutáneas Bacterianas/microbiología , Enfermedades Cutáneas Bacterianas/prevención & control , Infecciones Estreptocócicas/microbiología , Infecciones Estreptocócicas/prevención & control , Streptococcus pyogenes/patogenicidad , Vacunas de Subunidad/inmunología , Vacunas Sintéticas/inmunología , Factores de Virulencia/biosíntesis , Factores de Virulencia/genética , Factores de Virulencia/inmunología
15.
J Immunol ; 194(12): 5915-25, 2015 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-25980008

RESUMEN

Infections caused by Streptococcus pyogenes (group A Streptococcus [GAS]) are highly prevalent in the tropics, in developing countries, and in the Indigenous populations of developed countries. These infections and their sequelae are responsible for almost 500,000 lives lost prematurely each year. A synthetic peptide vaccine (J8-DT) from the conserved region of the M protein has shown efficacy against disease that follows i.p. inoculation of bacteria. By developing a murine model for infection that closely mimics human skin infection, we show that the vaccine can protect against pyoderma and subsequent bacteremia caused by multiple GAS strains, including strains endemic in Aboriginal communities in the Northern Territory of Australia. However, the vaccine was ineffective against a hypervirulent cluster of virulence responder/sensor mutant GAS strain; this correlated with the strain's ability to degrade CXC chemokines, thereby preventing neutrophil chemotaxis. By combining J8-DT with an inactive form of the streptococcal CXC protease, S. pyogenes cell envelope proteinase, we developed a combination vaccine that is highly effective in blocking CXC chemokine degradation and permits opsonic Abs to kill the bacteria. Mice receiving the combination vaccine were strongly protected against pyoderma and bacteremia, as evidenced by a 100-1000-fold reduction in bacterial burden following challenge. To our knowledge, a vaccine requiring Abs to target two independent virulence factors of an organism is unique.


Asunto(s)
Bacteriemia , Piodermia/prevención & control , Vacunas Estreptocócicas/inmunología , Streptococcus/inmunología , Vacunas Sintéticas/inmunología , Animales , Anticuerpos Antibacterianos/inmunología , Antígenos Bacterianos/química , Antígenos Bacterianos/inmunología , Proteínas de la Membrana Bacteriana Externa/química , Proteínas de la Membrana Bacteriana Externa/inmunología , Proteínas Portadoras/química , Proteínas Portadoras/inmunología , Modelos Animales de Enfermedad , Femenino , Inmunidad Innata , Memoria Inmunológica , Macrófagos/inmunología , Ratones , Neutrófilos/inmunología , Péptidos/inmunología , Piodermia/patología , Proteínas Recombinantes/inmunología , Infecciones Cutáneas Estafilocócicas/patología , Infecciones Cutáneas Estafilocócicas/prevención & control , Vacunas Estreptocócicas/genética , Vacunas Sintéticas/genética
16.
Regul Toxicol Pharmacol ; 91: 179-189, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29080846

RESUMEN

Oral paclitaxel (PTXL) formulations freed from cremophor® EL (CrEL) is always in utmost demand by the cancerous patients due to toxicities associated with the currently marketed formulation. In our previous investigation [Int. J. Pharm. 2014; 460:131], we have developed an oral oil based nanocarrier for the lipophilic drug, PTXL to target bioavailability issue and patient compliance. Here, we report in vivo antitumor activity and 28-day sub-chronic toxicity of the developed PTXL nanoemulsion. It was observed that the apoptotic potential of oral PTXL nanoemulsion significantly inhibited the growth of solid tumor (59.2 ± 7.17%; p < 0.001) without causing any explicit toxicity. The 6.5 mg/kg and 3 mg/kg oral PTXL nanoemulsion dose did not cause any notable alteration in haematological, biochemical/structural characteristics during 28-day sub-chronic toxicity studies in the experimental mice. Whereas, the toxicity of 12.8 mg/kg body weight dose showed decrease in RBC, haemoglobin and neutrophil counts. In contrast, marketed PTXL (Taxol®) was found to be comparatively more toxic to the experimental animals. Taxol® treatment resulted glomerulonephritis in histopathological examination, which could be correlated with increased level of creatinine and associated nephrotoxicity. This investigations conclude that the developed oral nanoemulsion presents a viable therapeutics bio-system to step towards clinical application as well as substitute CrEL based PTXL formulations.


Asunto(s)
Lesión Renal Aguda/inducido químicamente , Antineoplásicos Fitogénicos/farmacología , Portadores de Fármacos/química , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Paclitaxel/farmacología , Administración Oral , Animales , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/química , Apoptosis/efectos de los fármacos , Disponibilidad Biológica , Química Farmacéutica/métodos , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos/métodos , Emulsiones/efectos adversos , Emulsiones/química , Emulsiones/farmacología , Eritrocitos/efectos de los fármacos , Femenino , Hemoglobinas/metabolismo , Masculino , Ratones , Neoplasias/metabolismo , Neutrófilos/efectos de los fármacos , Paclitaxel/efectos adversos , Paclitaxel/química , Polietilenglicoles/química
17.
J Immunol ; 190(6): 2692-701, 2013 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-23401589

RESUMEN

Streptococcus pyogenes (group A Streptococcus [GAS]) is a leading human pathogen associated with a diverse array of mucosal and systemic infections. Vaccination with J8, a conserved region synthetic peptide derived from the M-protein of GAS and containing only 12 aa from GAS, when conjugated to diphtheria toxoid, has been shown to protect mice against a lethal GAS challenge. Protection has been previously shown to be Ab-mediated. J8 does not contain a dominant GAS-specific T cell epitope. The current study examined long-term Ab memory and dissected the role of B and T cells. Our results demonstrated that vaccination generates specific memory B cells (MBC) and long-lasting Ab responses. The MBC response can be activated following boost with Ag or limiting numbers of whole bacteria. We further show that these memory responses protect against systemic infection with GAS. T cell help is required for activation of MBC but can be provided by naive T cells responding directly to GAS at the time of infection. Thus, individuals whose T cells do not recognize the short synthetic peptide in the vaccine will be able to generate a protective and rapid memory Ab response at the time of infection. These studies significantly strengthen previous findings, which showed that protection by the J8-diphtheria toxoid vaccine is Ab-mediated and suggest that in vaccine design for other organisms the source of T cell help for Ab responses need not be limited to sequences from the organism itself.


Asunto(s)
Anticuerpos Antibacterianos/biosíntesis , Subgrupos de Linfocitos B/inmunología , Subgrupos de Linfocitos B/microbiología , Memoria Inmunológica/inmunología , Infecciones Estreptocócicas/prevención & control , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Colaboradores-Inductores/microbiología , Vacunas de Subunidad/administración & dosificación , Animales , Anticuerpos Antibacterianos/administración & dosificación , Subgrupos de Linfocitos B/metabolismo , Inmunización Secundaria/métodos , Ratones , Ratones Endogámicos BALB C , Ratones SCID , Infecciones Estreptocócicas/inmunología , Infecciones Estreptocócicas/microbiología , Factores de Tiempo , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/uso terapéutico
18.
Mol Pharm ; 11(10): 3596-608, 2014 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-25157890

RESUMEN

The objective of this study is to synthesize and evaluate acute toxicity of the bacterial cellulose (BC)/acrylamide (Am) hydrogels as noncytotoxic and biocompatible oral drug delivery vehicles. A novel series of solubilized BC/Am hydrogels were synthesized using a microwave irradiation method. The hydrogels were characterized by Fourier transform infrared spectroscopy (FTIR), swelling ratio, porosity, drug release, and in vitro and in vivo biocompatibility experiments. FTIR spectra revealed that the BC crystallinity and gel fraction decreased as the NaOH concentration increased from 2% to 10% w/v, whereas the optical transparency, pH sensitivity, and porosity were enhanced with increasing alkali concentration. Theophylline was used as a model drug for drug loading and release studies. The percentage of drug released was higher at pH 7.4 compared to pH 1.5. In vitro cytotoxicity and hemolytic tests indicated that the BC/Am hydrogel is noncytotoxic and hemocompatible. Results of acute oral toxicity tests on ICR mice suggested that the hydrogels are nontoxic up to 2000 mg/kg when administered orally, as no toxic response or histopathological changes were observed in comparison to control mice. The results of this study demonstrated that the pH-sensitive smart hydrogel makes it a possible safe carrier for oral drug delivery.


Asunto(s)
Acrilamida/química , Celulosa/química , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Hidrogel de Polietilenoglicol-Dimetacrilato/efectos adversos , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Animales , Portadores de Fármacos/efectos adversos , Sistemas de Liberación de Medicamentos/efectos adversos , Femenino , Concentración de Iones de Hidrógeno , Ratones , Ratones Endogámicos ICR
19.
Drug Dev Ind Pharm ; 40(10): 1340-9, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23875787

RESUMEN

This study evaluated the potential of stimuli-responsive bacterial cellulose-g-poly(acrylic acid-co-acrylamide) hydrogels as oral controlled-release drug delivery carriers. Hydrogels were synthesized by graft copolymerization of the monomers onto bacterial cellulose (BC) fibers by using a microwave irradiation technique. The hydrogels were characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). FT-IR spectroscopy confirmed the grafting. XRD showed that the crystallinity of BC was reduced by grafting, whereas an increase in the thermal stability profile was observed in TGA. SEM showed that the hydrogels exhibited a highly porous morphology, which is suitable for drug loading. The hydrogels demonstrated a pH-responsive swelling behavior, with decreased swelling in acidic media, which increased with increase in pH of the media, reaching maximum swelling at pH 7. The release profile of the hydrogels was investigated in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). The hydrogels showed lesser release in SGF than in SIF, suggesting that hydrogels may be suitable drug carriers for oral controlled release of drug delivery in the lower gastrointestinal tract.


Asunto(s)
Acrilamidas/química , Celulosa/química , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Administración Oral , Cristalización , Preparaciones de Acción Retardada , Jugo Gástrico/metabolismo , Hidrogeles , Concentración de Iones de Hidrógeno , Secreciones Intestinales/metabolismo , Microscopía Electrónica de Rastreo , Polimerizacion , Porosidad , Termogravimetría , Difracción de Rayos X
20.
Expert Opin Drug Discov ; 19(3): 303-316, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38112196

RESUMEN

INTRODUCTION: Owing to limited efficient treatment strategies for highly prevalent and distressing Parkinson's disease (PD), an impending need emerged for deciphering new modes and mechanisms for effective management. SH-SY5Y-based in vitro neuronal models have emerged as a new possibility for the elucidation of cellular and molecular processes in the pathogenesis of PD. SH-SY5Y cells are of human origin, adhered to catecholaminergic neuronal attributes, which consequences in imparting wide acceptance and significance to this model over conventional in vitro PD models for high-throughput screening of therapeutics. AREAS COVERED: Herein, the authors review the SH-SY5Y cell line and its value to PD research. The authors also provide the reader with their expert perspectives on how these developments can lead to the development of new impactful therapeutics. EXPERT OPINION: Encouraged by recent research on SH-SY5Y cell lines, it was envisaged that this in vitro model can serve as a primary model for assessing efficacy and toxicity of new therapeutics as well as for nanocarriers' capacity in delivering therapeutic agents across BBB. Considering the proximity with human neuronal environment as in pathogenic PD conditions, SH-SY5Y cell lines vindicated consistency and reproducibility in experimental results. Accordingly, exploitation of this standardized SH-SY5Y cell line can fast-track the drug discovery and development path for novel therapeutics.


Asunto(s)
Neuroblastoma , Enfermedad de Parkinson , Humanos , Línea Celular Tumoral , Enfermedad de Parkinson/tratamiento farmacológico , Reproducibilidad de los Resultados , Neuroblastoma/metabolismo , Neuroblastoma/patología , Descubrimiento de Drogas
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA