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1.
Crit Rev Microbiol ; : 1-16, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39161187

RESUMO

In recent times, the nasal region has emerged as a distinctive and dynamic environment where a myriad of microbial communities establish residence from infancy, persisting as both commensal and opportunistic pathogens throughout the lifespan. Understanding the coexistence of microorganisms in respiratory mucosal layers, their potential for infections, and the underlying molecular mechanisms shaping these interactions is crucial for developing efficient diagnostic and therapeutic interventions against respiratory and neurodegenerative diseases. Despite significant strides in understanding the olfactory system's nexus with nasal microbiota, comprehensive correlations with neurological diseases still need to be discovered. The nasal microbiome, a sentinel in immune defense, orchestrates a delicate equilibrium that, when disrupted, can precipitate severe respiratory infections, including Chronic Rhinosinusitis, Chronic obstructive pulmonary disorder (COPD), and Asthma, and instigate a cascade effect on central nervous system diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Multiple sclerosis (MS). This review aims to redress this imbalance by meticulously exploring the anatomical and microbiological nuances of the nasal mucosal surface in health and disease. By delineating the molecular intricacies of these interactions, this review unravels the molecular mechanisms that govern the intricate nexus between nasal microbiota dysbiosis, olfactory dysfunction, and the progression of respiratory and neurological diseases.

2.
Drug Dev Ind Pharm ; 50(2): 89-101, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38175566

RESUMO

OBJECTIVE: Vitamin D (a prohormone) is an important micronutrient required by the body for skeletal homeostasis and a range of non-skeletal actions. Calcitriol, the active form of vitamin D, regulates a variety of cellular and metabolic processes through both genomic and nongenomic pathways. Often prescribed for treating rickets and osteoporosis, vitamin D deficiency can exacerbate various other medical conditions. SIGNIFICANCE, METHODS, AND RESULTS: Despite its multifunctional uses, the sensitivity of vitamin D makes formulating an efficient drug delivery system a challenging task, which is further complicated by its poor aqueous solubility. Enhancing the oral absorption of vitamin D is vital in utilizing its full efficacy. Recent developments in encapsulation and nanotechnology have shown promising results in overcoming these constraints. CONCLUSION: This review thus offers an insight to adequately comprehend the mechanistic pharmacology of vitamin D, its pathophysiological role, and justification of its medical indications, along with the benefits of utilizing nanotechnology for vitamin D delivery.


Assuntos
Deficiência de Vitamina D , Vitamina D , Humanos , Vitamina D/metabolismo , Vitamina D/uso terapêutico , Alimentos Fortificados , Calcitriol/fisiologia , Calcitriol/uso terapêutico , Vitaminas , Deficiência de Vitamina D/tratamento farmacológico
3.
World J Surg ; 47(8): 1881-1898, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37277506

RESUMO

BACKGROUND: This is Part 3 of the first consensus guidelines for optimal care of patients undergoing emergency laparotomy using an enhanced recovery after surgery (ERAS) approach. This paper addresses organizational aspects of care. METHODS: Experts in management of the high-risk and emergency general surgical patient were invited to contribute by the International ERAS® Society. PubMed, Cochrane, Embase, and MEDLINE database searches were performed for ERAS elements and relevant specific topics. Studies were selected with particular attention to randomized clinical trials, systematic reviews, meta-analyses and large cohort studies, and reviewed and graded using the Grading of Recommendations, Assessment, Development and Evaluation system. Recommendations were made on the best level of evidence, or extrapolation from studies on elective patients when appropriate. A modified Delphi method was used to validate final recommendations. RESULTS: Components of organizational aspects of care were considered. Consensus was reached after three rounds of a modified Delphi process. CONCLUSIONS: These guidelines are based on best current available evidence for organizational aspects of an ERAS® approach to patients undergoing emergency laparotomy and include discussion of less common aspects of care for the surgical patient, including end-of-life issues. These guidelines are not exhaustive but pull together evidence on important components of care for this high-risk patient population. As much of the evidence is extrapolated from elective surgery or emergency general surgery (not specifically laparotomy), many of the components need further evaluation in future studies.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Humanos , Laparotomia , Assistência Perioperatória/métodos , Organizações , Procedimentos Cirúrgicos Eletivos
4.
World J Surg ; 47(8): 1850-1880, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37277507

RESUMO

BACKGROUND: This is Part 2 of the first consensus guidelines for optimal care of patients undergoing emergency laparotomy (EL) using an Enhanced Recovery After Surgery (ERAS) approach. This paper addresses intra- and postoperative aspects of care. METHODS: Experts in aspects of management of high-risk and emergency general surgical patients were invited to contribute by the International ERAS® Society. PubMed, Cochrane, Embase, and Medline database searches were performed for ERAS elements and relevant specific topics. Studies on each item were selected with particular attention to randomized clinical trials, systematic reviews, meta-analyses, and large cohort studies and reviewed and graded using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Recommendations were made on the best level of evidence, or extrapolation from studies on elective patients when appropriate. A modified Delphi method was used to validate final recommendations. Some ERAS® components covered in other guideline papers are outlined only briefly, with the bulk of the text focusing on key areas pertaining specifically to EL. RESULTS: Twenty-three components of intraoperative and postoperative care were defined. Consensus was reached after three rounds of a modified Delphi Process. CONCLUSIONS: These guidelines are based on best available evidence for an ERAS® approach to patients undergoing EL. These guidelines are not exhaustive but pull together evidence on important components of care for this high-risk patient population. As much of the evidence is extrapolated from elective surgery or emergency general surgery (not specifically laparotomy), many of the components need further evaluation in future studies.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Humanos , Cuidados Pós-Operatórios , Laparotomia , Assistência Perioperatória/métodos , Procedimentos Cirúrgicos Eletivos/métodos
5.
Drug Resist Updat ; 65: 100889, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36403342

RESUMO

Multi-drug resistance (MDR) developed in response to chemotherapy is one of the prominent causes of therapeutic failure. The major underlying factors that contribute to such malignancies include tumor microenvironment, genetic alterations, changes at the cellular level and most of all the heterogeneity of tumors. Recent advances in the field of oncology have prompted a mechanistic understanding of the human genome which is responsible for such alterations, upon which the therapy would be designed. Such an approach that administers drugs by targeting the molecular changes is attributed to precision medicine. Precision medicine helps design therapy as per the requirement of patients based on the sharing of similar complex tumor environments. This revolutionized approach would help in early detection, better targeting, improved patient compliance and survival along with much reduced toxicity otherwise evidenced in conventional cancer therapy. This review discusses the cause of MDR, highlighting the role of precision medicine in overcoming such critical events. Major limitations and future prospects are also highlighted.


Assuntos
Neoplasias , Medicina de Precisão , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Oncologia , Microambiente Tumoral/genética , Resistência a Múltiplos Medicamentos/genética
6.
J Generic Med ; 19(2): 66-74, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38603246

RESUMO

Nutraceuticals are essentially nutritional components that have a vital role in developing and maintaining the body's regular functions, which keeps people healthy. The nutraceutical sector is also primarily driven by the existing global population and trends. Examples of foods considered as nutraceuticals include prebiotics, fibre, polyunsaturated fatty acids, probiotics, antioxidants, and other natural or herbal foods. Some of the most serious health problems of the 20th century, like COVID-19 and diabetes mellitus, are managed with the help of the preceding nutraceuticals. As we move into a time of health and medicine, the food industry as a whole has become more focused on research.

7.
Molecules ; 27(5)2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35268826

RESUMO

Oral diseases pose a major threat to public health across the globe. Diseases such as dental caries, periodontitis, gingivitis, halitosis, and oral cancer affect people of all age groups. Moreover, unhealthy diet practices and the presence of comorbidities aggravate the problem even further. Traditional practices such as the use of miswak for oral hygiene and cloves for toothache have been used for a long time. The present review exhaustively explains the potential of natural products obtained from different sources for the prevention and treatment of dental diseases. Additionally, natural medicine has shown activity in preventing bacterial biofilm resistance and can be one of the major forerunners in the treatment of oral infections. However, in spite of the enormous potential, it is a less explored area due to many setbacks, such as unfavorable physicochemical and pharmacokinetic properties. Nanotechnology has led to many advances in the dental industry, with various applications ranging from maintenance to restoration. However, can nanotechnology help in enhancing the safety and efficacy of natural products? The present review discusses these issues in detail.


Assuntos
Saúde Bucal
8.
World J Surg ; 45(5): 1272-1290, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33677649

RESUMO

BACKGROUND: Enhanced Recovery After Surgery (ERAS) protocols reduce length of stay, complications and costs for a large number of elective surgical procedures. A similar, structured approach appears to improve outcomes, including mortality, for patients undergoing high-risk emergency general surgery, and specifically emergency laparotomy. These are the first consensus guidelines for optimal care of these patients using an ERAS approach. METHODS: Experts in aspects of management of the high-risk and emergency general surgical patient were invited to contribute by the International ERAS® Society. Pubmed, Cochrane, Embase, and MEDLINE database searches on English language publications were performed for ERAS elements and relevant specific topics. Studies on each item were selected with particular attention to randomized controlled trials, systematic reviews, meta-analyses and large cohort studies, and reviewed and graded using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Recommendations were made on the best level of evidence, or extrapolation from studies on non-emergency patients when appropriate. The Delphi method was used to validate final recommendations. The guideline has been divided into two parts: Part 1-Preoperative Care and Part 2-Intraoperative and Postoperative management. This paper provides guidelines for Part 1. RESULTS: Twelve components of preoperative care were considered. Consensus was reached after three rounds. CONCLUSIONS: These guidelines are based on the best available evidence for an ERAS approach to patients undergoing emergency laparotomy. Initial management is particularly important for patients with sepsis and physiological derangement. These guidelines should be used to improve outcomes for these high-risk patients.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Procedimentos Cirúrgicos Eletivos , Humanos , Laparotomia , Tempo de Internação , Assistência Perioperatória , Complicações Pós-Operatórias , Cuidados Pré-Operatórios
9.
Int J Pharm ; 664: 124588, 2024 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-39153644

RESUMO

This study investigates the biodistribution of a nano lipid carrier system (NLCs) containing the hydrophobic drug erlotinib (ERL-NLCs). The system was labelled with the fluorescent dye IR-780 for real-time dynamic imaging. ERL-NLCs were initially developed using the ultrasonication method with oleic acid and stearic acid. In vitro and ex vivo studies were performed to confirm the formation and penetration of NLCs within the intestine. Subsequently, the biological distribution of ERL-NLCs was monitored using a fluorescent dye through the IVIS® fluorescent optical imaging technique in whole live animals. Mice were orally administered blank IR 780 dye solution, ERL suspension, and IR 780 labelled NLCs. Fluorescence images were acquired at different time intervals up to 24 h and then total radiant efficiency was calculated through the region of interest (ROI) of the whole animal at each interval of time for all three groups. To validate the results obtained from in vivo imaging, various organs including lungs, heart, liver, both kidneys, stomach, and intestine were subsequently extracted and examined after 24 h. The ROI was found to be higher in the blank IR 780 dye solution, followed by the drug suspension and IR 780 labelled NLCs. These results confirm that the plain ERL suspension distributes across the body, and its encapsulation in NLCs facilitates passage through the lymphatic intestinal pathway, effectively avoiding first-pass metabolism. The remarkable results indicated that the NLCs formulation effectively circumvents first-pass metabolism by adopting the intestinal lymphatic pathway, thereby enhancing the oral bioavailability of the drug. This observed behaviour underscores the potential of NLCs in optimizing drug delivery and minimizing adverse effects associated with gastrointestinal and metabolic processes.


Assuntos
Portadores de Fármacos , Cloridrato de Erlotinib , Corantes Fluorescentes , Nanopartículas , Imagem Óptica , Animais , Cloridrato de Erlotinib/administração & dosagem , Cloridrato de Erlotinib/farmacocinética , Distribuição Tecidual , Corantes Fluorescentes/administração & dosagem , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacocinética , Administração Oral , Portadores de Fármacos/química , Imagem Óptica/métodos , Camundongos , Nanopartículas/química , Lipídeos/química , Indóis/farmacocinética , Indóis/administração & dosagem , Indóis/química , Ácido Oleico/química , Masculino
10.
Infect Disord Drug Targets ; 24(7): e020224226666, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38305295

RESUMO

The global prevalence of fungal infections is alarming in both the pre- and post- COVID period. Due to a limited number of antifungal drugs, there are hurdles in treatment strategies for fungal infections due to toxic potential, drug interactions, and the development of fungal resistance. All the antifungal targets (existing and newer) and pipeline molecules showing promise against these targets are reviewed. The objective was to predict or repurpose phyto-based antifungal compounds based on a dual target inhibition approach (Sterol-14-α- demethylase and HSP-90) using a case study. In pursuit of repurposing the phytochemicals as antifungal agents, a team of researchers visited Aravalli Biodiversity Park (ABP), Delhi, India, to collect information on available medicinal plants. From 45 plants, a total of 1149 ligands were collected, and virtual screening was performed using Schrodinger Suite 2016 software to get 83 hits against both the target proteins: Sterol-14-α-demethylase and HSP-90. After analysis of docking results, ligands were selected based on their interaction against both the target proteins and comparison with respective standard ligands (fluconazole and ganetespib). We have selected Isocarthamidin, Quercetin and Boeravinone B based on their docking score and binding interaction against the HSP-90 (Docking Score -9.65, -9.22 and -9.21, respectively) and 14-α-demethylase (Docking Score -9.19, -10.76 and -9.74 respectively). The docking protocol was validated and MM/GBSA studies depicted better stability of selected three ligands (Isocarthamidin, Quercetin, Boeravinone B) complex as compared to standard complex. Further, MD simulation studies were performed using the Desmond (67) software package version 2018-4. All the findings are presented as a case study for the prediction of dual targets for the repurposing of certain phytochemicals as antifungal agents.


Assuntos
Antifúngicos , Reposicionamento de Medicamentos , Simulação de Acoplamento Molecular , Compostos Fitoquímicos , Antifúngicos/farmacologia , Antifúngicos/química , Índia , Humanos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Esterol 14-Desmetilase/metabolismo , Esterol 14-Desmetilase/química , Plantas Medicinais/química , Quercetina/farmacologia , Quercetina/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Micoses/tratamento farmacológico , Micoses/microbiologia
11.
Med Oncol ; 41(7): 173, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38864966

RESUMO

Erlotinib (ELB) is a tyrosine kinase inhibitor that targets the activity of Epidermal Growth Factor Receptor (EGFR) protein found in both healthy and cancerous cells. It binds reversibly to the ATP-binding site of the EGFR tyrosine kinase. ELB was approved by the US Food and Drug Administration (FDA) in 2004 for advanced non-small cell lung cancer (NSCLC) treatment in patients who relapsed after at least one other therapy. It was authorized for use with gemcitabine in 2005 for the treatment of advanced pancreatic cancer. In addition to lung cancer, ELB has shown promising results in the treatment of other cancers, including breast, prostate, colon, pancreatic, cervical, ovarian, and head and neck cancers. However, its limited water solubility, as a BCS class II drug, presents biopharmaceutical problems. Nanoformulations have been developed to overcome these issues, including increased solubility, controlled release, enhanced stability, tumor accumulation, reduced toxicity, and overcoming drug resistance. In older patients, ELB management should involve individualized dosing based on age-related changes in drug metabolism and close monitoring for adverse effects. Regular assessments of renal and hepatic functions are essential. This review provides an overview of ELB's role of ELB in treating various cancers, its associated biopharmaceutical issues, and the latest developments in ELB-related nanotechnology interventions. It also covers ELB patents granted in previous years and the ongoing clinical trials.


Assuntos
Ensaios Clínicos como Assunto , Cloridrato de Erlotinib , Neoplasias , Inibidores de Proteínas Quinases , Humanos , Cloridrato de Erlotinib/uso terapêutico , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Antineoplásicos/uso terapêutico , Nanotecnologia/métodos , Patentes como Assunto , Receptores ErbB/antagonistas & inibidores
12.
Nanomedicine (Lond) ; 19(18-20): 1659-1673, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39056145

RESUMO

Aim: The aim of this study was to optimize, develop, characterize and evaluate a topical nanobigel (BG) formulation containing Berberine (BRB) that exhibits anti-melanogenic properties.Materials & methods: The Berberine-loaded bigel (BRB@BG) formulation was prepared by homogenously mixing the optimized hydrogel and oleogel. BRB@BG was characterized in vitro and cytotoxicity study was conducted to evaluate its effects on murine skin melanoma B16F10 cell lines.Results: The optimized BRB@BG exhibited uniform texture with nanometric size, desirable spreadability and extrudability, suitable for topical applications. Cytotoxicity studies revealed that BRB@BG had a lower IC50 value (4.84 µg/ml) on B16F10 cell lines compared with drug alone.Conclusion: In conclusion, the developed BRB@BG formulation showed good potential as safe and effective topical treatment for hyperpigmentation.


Hyperpigmentation is a common skin disease in which the melanin content becomes abnormally high. The existing treatment options are associated with side effects and therefore research is being aimed to develop a topical nanoformulation based on natural compounds. Berberine (BRB) is one such natural compound that is known to inhibit the production of melanin in skin. This study was aimed to develop a bigel formulation of BRB that can be applied on skin, which can treat the hyperpigmentation and is safe. The developed nanomedicine was found to have all good properties of a topical formulation and was more effective than the drug alone. Various studies on animals were conducted to assess its safety and it was found that the formulation did not show any toxicity to the skin.


Assuntos
Berberina , Hiperpigmentação , Melanoma Experimental , Berberina/farmacologia , Berberina/administração & dosagem , Berberina/química , Animais , Camundongos , Linhagem Celular Tumoral , Hiperpigmentação/tratamento farmacológico , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Sobrevivência Celular/efeitos dos fármacos , Hidrogéis/química , Humanos , Portadores de Fármacos/química , Tamanho da Partícula
13.
Nanomedicine (Lond) ; 19(10): 855-874, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38440976

RESUMO

Aims: This study was aimed to formulate erlotinib (ERL)-loaded transferosomal gel (ERL@TG) intended for topical application for the treatment of ductal carcinoma in situ. Materials & methods: The optimized process involved a thin-film hydration method to generate ERL-loaded transferosomes (ERL@TFS), which was incorporated into a carbopol gel matrix to generate ERL@TG. The optimized formulation was characterized in vitro followed by cytotoxicity evaluation on MCF-7 breast cancer cell lines and acute toxicity and skin irritation studies was performed in vivo. Results: In a comparative assessment against plain ERL, ERL@TG displayed enhanced efficacy against MCF-7 cell lines, reflected in considerably lower IC50 values with an enhanced safety profile. Conclusion: Optimized ERL@TG was identified as a promising avenue for addressing ductal carcinoma in situ breast cancer.


Despite progress, breast cancer remains a significant cause of death. This study aimed to revolutionize the treatment of noninvasive ductal carcinoma in situ, a type of breast cancer, by developing a special gel that can be applied directly to the breast. The developed gel was in the nanoform, a 'nanotransfersomal' gel that contained erlotinib, a potent drug for breast cancer. To ensure its effectiveness, we evaluated the erlotinib-loaded transfersomal gel through various tests. The results confirmed that the gel was nano-sized and loaded with a high amount of erlotinib. Animal studies were conducted to check if the prepared gel caused any skin irritation and interestingly, there was no irritation observed on the animals' skin. Furthermore, we treated breast cancer cells with the developed gel using a method called MTT assay and the results showed improved cell-killing activity in comparison to plain drug. In conclusion, this special gel represents a breakthrough in breast cancer treatment. It offers hope for better outcomes in the fight against this disease. This innovative approach involves directly applying the gel on the affected area topically to increase patient compliance and decreasing side effects of drugs. This could potentially transform ductal carcinoma in situ breast cancer treatment, bringing us closer to improved treatments and outcomes.


Assuntos
Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Humanos , Feminino , Cloridrato de Erlotinib/uso terapêutico , Linhagem Celular Tumoral , Lipossomos , Neoplasias da Mama/tratamento farmacológico
14.
Int J Hypertens ; 2024: 2430147, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38410720

RESUMO

The lipid-based drug delivery system (LBDDS) is a well-established technique that is anticipated to bring about comprehensive transformations in the pharmaceutical field, impacting the management and administration of drugs, as well as treatment and diagnosis. Various LBDDSs verified to be an efficacious mechanism for monitoring hypertension systems are SEDDS (self-nano emulsifying drug delivery), nanoemulsion, microemulsions, vesicular systems (transferosomes and liposomes), and solid lipid nanoparticles. LBDDSs overcome the shortcomings that are associated with antihypertensive agents because around fifty percent of the antihypertensive agents experience a few drawbacks including short half-life because of hepatic first-pass metabolism, poor aqueous solubility, low permeation rate, and undesirable side effects. This review emphasizes antihypertensive agents that were encapsulated into the lipid carrier to improve their poor oral bioavailability. Incorporating cutting-edge technologies such as nanotechnology and targeted drug delivery, LBDDS holds promise in addressing the multifactorial nature of hypertension. By fine-tuning drug release profiles and enhancing drug uptake at specific sites, LBDDS can potentially target renin-angiotensin-aldosterone system components, sympathetic nervous system pathways, and endothelial dysfunction, all of which play crucial roles in hypertension pathophysiology. The future of hypertension management using LBDDS is promising, with ongoing reviews focusing on precision medicine approaches, improved biocompatibility, and reduced toxicity. As we delve deeper into understanding the intricate mechanisms underlying hypertension, LBDDS offers a pathway to develop next-generation antihypertensive therapies that are safer, more effective, and tailored to individual patient needs.

15.
Int J Cardiol ; 414: 132418, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39121919

RESUMO

For many years, clopidogrel has been a commonly utilised antiplatelet drug in the management of coronary artery disease (CAD). It's thought that the CYP2C19 loss of function (LoF) polymorphism causes clopidogrel's poor metabolism, which eventually leads to resistance. Previous research produced extremely divergent and inconsistent results, making it impossible to draw definitive conclusions. Therefore, current, investigation was carried out to obtain definitive evidence from an updated meta-analysis on the connection between CYP2C19 LoF polymorphism and coronary artery event in patients treated with clopidogrel. 52,542 individuals with coronary artery disease who were receiving clopidogrel treatment were included in 87 carefully chosen trials from reliable databases that we used for our meta-analysis. According to our data, those who carry one or more CYP2C19 LoF alleles worldwide are much more likely to experience composite events and coronary artery events than people who do not carry these alleles, especially in Asian populations. Our meta-analysis observed that the global population, particularly Asians receiving clopidogrel treatment, is at risk of recurrent coronary artery events and composite events if they carry the CYP2C19 LoF alleles. Additional research is essential on alternative antiplatelet therapies for individuals who exhibit poor or intermediate metabolic activity. OBJECTIVES: 1.To systematically analyze the current evidence regarding the association of CYP2C19 variants with coronary artery disease (CAD). 2.To conduct a meta-analysis to investigate the association between loss of function (LoF) CYP2C19 modifications and CAD.


Assuntos
Clopidogrel , Doença da Artéria Coronariana , Citocromo P-450 CYP2C19 , Inibidores da Agregação Plaquetária , Humanos , Citocromo P-450 CYP2C19/genética , Clopidogrel/uso terapêutico , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Resultado do Tratamento , Mutação com Perda de Função
16.
Drug Dev Ind Pharm ; 39(1): 39-50, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22335586

RESUMO

The efficacy of oral risperidone treatment in prevention of schizophrenia is well known. However, oral side effects and patient compliance is always a problem for schizophrenics. In this study, risperidone was formulated into matrix transdermal patches to overcome these problems. The formulation factors for such patches, including eudragit RL 100 and eudragit RS 100 as matrix forming polymers, olive oil, groundnut oil and jojoba oil in different concentrations as enhancers and amount of drug loaded were investigated. The transdermal patches containing risperidone were prepared by solvent casting method and characterized for physicochemical and in vitro permeation studies through excised rat skin. Among the tested preparations, formulations with 20% risperidone, 3:2 ERL 100 and ERS 100 as polymers, mixture of olive oil and jojoba oil as enhancer, exhibited greatest cumulative amount of drug permeated (1.87 ± 0.09 mg/cm(2)) in 72 h, so batch ROJ was concluded as optimized formulation and assessed for pharmacokinetic, pharmacodynamic and skin irritation potential. The pharmacokinetic characteristics of the optimized risperidone patch were determined using rabbits, while orally administered risperidone in solution was used for comparison. The calculated relative bioavailability of risperidone transdermal patch was 115.20% with prolonged release of drug. Neuroleptic efficacy of transdermal formulation was assessed by rota-rod and grip test in comparison with control and marketed oral formulations with no skin irritation. This suggests the transdermal application of risperidone holds promise for improved bioavailability and better management of schizophrenia in long-term basis.


Assuntos
Antipsicóticos/farmacocinética , Risperidona/farmacocinética , Adesivo Transdérmico , Animais , Antipsicóticos/farmacologia , Disponibilidade Biológica , Feminino , Masculino , Camundongos , Olea , Óleo de Amendoim , Permeabilidade , Óleos de Plantas/farmacocinética , Óleos de Plantas/farmacologia , Ácidos Polimetacrílicos/farmacocinética , Ácidos Polimetacrílicos/farmacologia , Coelhos , Ratos , Ratos Wistar , Risperidona/farmacologia , Pele/efeitos dos fármacos , Ceras
17.
Pharm Dev Technol ; 18(4): 916-25, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-21913873

RESUMO

Transdermal patches of olanzapine were aimed to be prepared to overcome the side effects by oral application. The strategy was formulation of eudragit-based polymeric films to prepare transdermal patches by using nonionic (span-20), anionic (sodium lauryl sulfate), cationic surfactant (benzalkonium chloride), and vegetable oil (olive oil) as permeation enhancers. The patches were subjected to physicochemical, in vitro release and ex vivo permeation studies. On the basis of in vitro release performance, ERL 100:ERS 100 in the ratio of 3:2 was selected for incorporation of permeation enhancers. The permeation studies showed that formulation containing 10% span 20 (OD3) exhibited greatest cumulative amount of drug permeated (19.02 ± 0.21 mg) in 72 h, so OD3 was concluded as optimized formulation and assessed for pharmacokinetic, pharmacodynamic, and skin irritation potential. In vivo studies of optimized olanzapine patch in rabbit model revealed prolongation of action with Frel 116.09% during 72-h study period. Neuroleptic efficacy of transdermal patch was comparable to oral formulation during rotarod and grip test in Wistar albino rats with no skin irritation. Thus, developed formulation of olanzapine is expected to improve the patient compliance, form better dosage regimen, and provide maintenance therapy to psychotic patients.


Assuntos
Antipsicóticos/administração & dosagem , Benzodiazepinas/administração & dosagem , Portadores de Fármacos/química , Excipientes/química , Resinas Acrílicas/química , Administração Cutânea , Animais , Antipsicóticos/farmacocinética , Antipsicóticos/farmacologia , Benzodiazepinas/farmacocinética , Benzodiazepinas/farmacologia , Preparações de Ação Retardada , Técnicas In Vitro , Camundongos , Olanzapina , Permeabilidade , Coelhos , Ratos , Ratos Wistar , Absorção Cutânea , Testes de Irritação da Pele , Tensoativos/química , Fatores de Tempo , Adesivo Transdérmico
18.
Asian J Pharm Sci ; 18(5): 100845, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37881798

RESUMO

RNA interference (RNAi) using small interfering RNA (siRNA) has shown potential as a therapeutic option for the treatment of arthritis by silencing specific genes. However, siRNA delivery faces several challenges, including stability, targeting, off-target effects, endosomal escape, immune response activation, intravascular degradation, and renal clearance. A variety of nanotherapeutics like lipidic nanoparticles, liposomes, polymeric nanoparticles, and solid lipid nanoparticles have been developed to improve siRNA cellular uptake, protect it from degradation, and enhance its therapeutic efficacy. Researchers are also investigating chemical modifications and bioconjugation to reduce its immunogenicity. This review discusses the potential of siRNA nanotherapeutics as a therapeutic option for various immune-mediated diseases, including rheumatoid arthritis, osteoarthritis, etc. siRNA nanotherapeutics have shown an upsurge of interest and the future looks promising for such interdisciplinary approach-based modalities that combine the principles of molecular biology, nanotechnology, and formulation sciences.

19.
Curr Drug Targets ; 24(1): 2-12, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36200208

RESUMO

Bone diseases such as rheumatoid arthritis, Paget's disease, and osteoporosis cause mortality and mobility limits. Nanomedicine and nano delivery systems have been utilised to deliver active drug moiety to the precisely targeted site in a controlled manner, and it serves as a means of diagnostic tools. The utilisation of nanomedicine is expanding vigorously for assured targeting and efficient drug delivery. Nanotechnology offers various advantages, such as site-specific targeting, precise drug release kinetics, and improved bone mineral density. Recent medications available for osteoporosis are not viable due to the adverse effects associated with them and low patient compliance. There is an urgent need to develop biocompatible and appropriate drug delivery nanocarriers such as nanoparticles, liposomes, hydrogels, dendrimers, micelles, mesoporous particles, etc. These carriers enhance drug delivery and therapeutic effectiveness in bone tissues. The use of nanotechnology is also associated with toxicity. This article presents the review of various reports on nanocarrier systems and biologics for the treatment of osteoporosis. It aims to provide researchers with a clue for inventing a new drug delivery system with site-specific targeting for the treatment of osteoporosis.


Assuntos
Nanopartículas , Osteoporose , Humanos , Sistemas de Liberação de Medicamentos , Nanotecnologia , Lipossomos , Nanomedicina , Nanopartículas/uso terapêutico , Osteoporose/tratamento farmacológico , Portadores de Fármacos
20.
Curr Drug Res Rev ; 15(3): 207-221, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36799415

RESUMO

Engulfing almost 537 million people, the most commonly occurring metabolic disorder, diabetes mellitus, is emerging as an epidemic worldwide. Diabetes mellitus is identified as a heterogeneous pathological condition that is marked by extreme hyperglycemic (glucose) levels caused by reduced insulin sensitivity. Synthetic antidiabetic medications are widely commercialized but have slowly expressed several inevitable side effects and limitations in treated diabetic subjects. Researchers have been exploring herbal medicine due to its esteemed therapeutic effects. WHO have enlisted almost 21,000 herbal components that have established therapeutic benefit. Several herbs, most of them widely available, have been studied to extract their active phytoconstituents that have effective diabetes management potential with the least risk factor for side effects and acute toxicity. Though acceptable standardization, awareness, and clinical trials are yet to be established before mainstreaming herbal formulation, preclinical studies have confirmed the higher safety and efficacy of several extracted phytoconstituents and formulation in comparative analysis with synthetic products. The authors have also discussed their opinions with regard to the vast usability of herbal components along with the multi-target functionality of several phytoconstituents, as well as the challenges faced for standardizing, formulating, and marketing herbal medicines. Other than this, several cases of clinical trials showing effectivity of herbal antidiabetic aid are mentioned. In this review, an attempt has been made to summarize the potential antidiabetic herbs, marketed herbal formulations, and patented formulations that have established therapeutic prospects to downregulate diabetic conditions.


Assuntos
Diabetes Mellitus , Plantas Medicinais , Humanos , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/induzido quimicamente , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Medicina Herbária , Insulina/uso terapêutico
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