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1.
Life Sci ; 345: 122613, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38582393

RESUMO

Glioblastoma (GBM) is the most prevalent and deadly primary brain tumor type, with a discouragingly low survival rate and few effective treatments. An important function of the EGFR signalling pathway in the development of GBM is to affect tumor proliferation, persistence, and treatment resistance. Advances in molecular biology in the last several years have shown how important ncRNAs are for controlling a wide range of biological activities, including cancer progression and development. NcRNAs have become important post-transcriptional regulators of gene expression, and they may affect the EGFR pathway by either directly targeting EGFR or by modifying important transcription factors and downstream signalling molecules. The EGFR pathway is aberrantly activated in response to the dysregulation of certain ncRNAs, which has been linked to GBM carcinogenesis, treatment resistance, and unfavourable patient outcomes. We review the literature on miRNAs, circRNAs and lncRNAs that are implicated in the regulation of EGFR signalling in GBM, discussing their mechanisms of action, interactions with the signalling pathway, and implications for GBM therapy. Furthermore, we explore the potential of ncRNA-based strategies to overcome resistance to EGFR-targeted therapies, including the use of ncRNA mimics or inhibitors to modulate the activity of key regulators within the pathway.


Assuntos
Neoplasias Encefálicas , Glioblastoma , MicroRNAs , Humanos , Receptores ErbB/metabolismo , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , Transdução de Sinais , MicroRNAs/metabolismo , RNA não Traduzido/genética , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo
2.
Chem Biol Interact ; 395: 111000, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38614318

RESUMO

Nucleic acid delivery by viral and non-viral methods has been a cornerstone for the contemporary gene therapy aimed at correcting the defective genes, replacing of the missing genes, or downregulating the expression of anomalous genes is highly desirable for the management of various diseases. Ostensibly, it becomes paramount for the delivery vectors to intersect the biological barriers for accessing their destined site within the cellular environment. However, the lipophilic nature of biological membranes and their potential to limit the entry of large sized, charged, hydrophilic molecules thus presenting a sizeable challenge for the cellular integration of negatively charged nucleic acids. Furthermore, the susceptibility of nucleic acids towards the degrading enzymes (nucleases) in the lysosomes present in cytoplasm is another matter of concern for their cellular and nuclear delivery. Hence, there is a pressing need for the identification and development of cationic delivery systems which encapsulate the cargo nucleic acids where the charge facilitates their cellular entry by evading the membrane barriers, and the encapsulation shields them from the enzymatic attack in cytoplasm. Cycloamylose bearing a closed loop conformation presents a robust candidature in this regard owing to its remarkable encapsulating tendency towards nucleic acids including siRNA, CpG DNA, and siRNA. The presence of numerous hydroxyl groups on the cycloamylose periphery provides sites for its chemical modification for the introduction of cationic groups, including spermine, (3-Chloro-2 hydroxypropyl) trimethylammonium chloride (Q188), and diethyl aminoethane (DEAE). The resulting cationic cycloamylose possesses a remarkable transfection efficiency and provides stability to cargo oligonucleotides against endonucleases, in addition to modulating the undesirable side effects such as unwanted immune stimulation. Cycloamylose is known to interact with the cell membranes where they release certain membrane components such as phospholipids and cholesterol thereby resulting in membrane destabilization and permeabilization. Furthermore, cycloamylose derivatives also serve as formulation excipients for improving the efficiency of other gene delivery systems. This review delves into the various vector and non-vector-based gene delivery systems, their advantages, and limitations, eventually leading to the identification of cycloamylose as an ideal candidate for nucleic acid delivery. The synthesis of cationic cycloamylose is briefly discussed in each section followed by its application for specific delivery/transfection of a particular nucleic acid.

3.
Noncoding RNA Res ; 9(2): 277-287, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38505309

RESUMO

The intricate molecular landscape of cancer pathogenesis continues to captivate researchers worldwide, with Circular RNAs (circRNAs) emerging as pivotal players in the dynamic regulation of biological functions. The study investigates the elusive link between circRNAs and the Transforming Growth Factor-ß (TGF-ß) signalling pathway, exploring their collective influence on cancer progression and metastasis. Our comprehensive investigation begins by profiling circRNA expression patterns in diverse cancer types, revealing a repertoire of circRNAs intricately linked to the TGF-ß pathway. Through integrated bioinformatics analyses and functional experiments, we elucidate the specific circRNA-mRNA interactions that modulate TGF-ß signalling, unveiling the regulatory controls governing this crucial pathway. Furthermore, we provide compelling evidence of the impact of circRNA-mediated TGF-ß modulation on key cellular processes, including epithelial-mesenchymal transition (EMT), migration, and cell proliferation. In addition to their mechanistic roles, circRNAs have shown promise as diagnostic and prognostic biomarkers, as well as potential molecular targets for cancer therapy. Their ability to modulate critical pathways, such as the TGF-ß signalling axis, underscores their significance in cancer biology and clinical applications. The intricate interplay between circRNAs and TGF-ß is dissected, uncovering novel regulatory circuits that contribute to the complexity of cancer biology. This review unravels a previously unexplored dimension of carcinogenesis, emphasizing the crucial role of circRNAs in shaping the TGF-ß signalling landscape.

4.
Curr Drug Deliv ; 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38445696

RESUMO

Chronic Obstructive Pulmonary Disease (COPD), a chronic lung disease that causes breathing difficulties and obstructs airflow from the lungs, has a significant global health burden and affects millions of people worldwide. The use of pharmaceuticals in COPD treatment is aimed to alleviate symptoms, improve lung function, prevent exacerbations, and enhance the overall quality of life for patients. Nanotechnology holds great promise to alleviate the burden of COPD. The main goal of this review is to present the full spectrum of therapeutics based on nanostructures for the treatment and management of COPD, including nanoparticles, polymeric nanoparticles, polymeric micelles, solid-lipid nanoparticles, liposomes, exosomes, nanoemulsions, nanosuspensions, and niosomes. Nanotechnology is just one of the many areas of research that may contribute to the development of more effective and personalized treatment modalities for COPD patients in the future. Future studies may be focused on enhancing the therapeutic effectiveness of nanocarriers by conducting extensive mechanistic investigations to translate current scientific knowledge for the effective management of COPD with little or no adverse effects.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38415490

RESUMO

BACKGROUND: A nanoemulsion is a colloidal system of small droplets dispersed in another liquid. It has attracted considerable attention due to its unique properties and various applications. Throughout this review, we provide an overview of nanoemulsions and how they can be applied to various applications such as drug delivery, food applications, and pesticide formulations. OBJECTIVE: This updated review aims to comprehensively overview nanoemulsions and their applications as a versatile platform for drug delivery, food applications, and pesticide formulations. METHODS: Research relevant scientific literature across various databases, including PubMed, Scopus, and Web of Science. Suitable keywords for this purpose include "nanoemulsion," "drug delivery," and "food applications." Ensure the search criteria include recent publications to ensure current knowledge is included. RESULTS: Several benefits have been demonstrated in the delivery of drugs using nanoemulsions, including improved solubility, increased bioavailability, and controlled delivery. Nanoemulsions have improved some bioactive compounds in food applications, including vitamins and antioxidants. At the same time, pesticide formulations based on nanoemulsions have also improved solubility, shelf life, and effectiveness. CONCLUSION: The versatility of nanoemulsions makes them ideal for drug delivery, food, and pesticide formulation applications. These products are highly soluble, bioavailable, and targeted, providing significant advantages. More research and development are required to implement nanoemulsion-based products on a commercial scale.

6.
Ageing Res Rev ; 95: 102236, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38369026

RESUMO

Recent studies have indicated the significant involvement of the gut microbiome in both human physiology and pathology. Additionally, therapeutic interventions based on microbiome approaches have been employed to enhance overall health and address various diseases including aging and neurodegenerative disease (ND). Researchers have explored potential links between these areas, investigating the potential pathogenic or therapeutic effects of intestinal microbiota in diseases. This article provides a summary of established interactions between the gut microbiome and ND. Post-biotic is believed to mediate its neuroprotection by elevating the level of dopamine and reducing the level of α-synuclein in substantia nigra, protecting the loss of dopaminergic neurons, reducing the aggregation of NFT, reducing the deposition of amyloid ß peptide plagues and ameliorating motor deficits. Moreover, mediates its neuroprotective activity by inhibiting the inflammatory response (decreasing the expression of TNFα, iNOS expression, free radical formation, overexpression of HIF-1α), apoptosis (i.e. active caspase-3, TNF-α, maintains the level of Bax/Bcl-2 ratio) and promoting BDNF secretion. It is also reported to have good antioxidant activity. This review offers an overview of the latest findings from both preclinical and clinical trials concerning the use of post-biotics in ND.


Assuntos
Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Doenças Neurodegenerativas/terapia , Doenças Neurodegenerativas/metabolismo , Peptídeos beta-Amiloides/metabolismo , Doença de Parkinson/metabolismo , Substância Negra/metabolismo , Neuroproteção
7.
Pathol Res Pract ; 255: 155157, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38320440

RESUMO

Lung cancer (LCs) is still a serious health problem globally, with many incidences attributed to environmental triggers such as Volatile Organic Compounds (VOCs). VOCs are a broad class of compounds that can be released via various sources, including industrial operations, automobile emissions, and indoor air pollution. VOC exposure has been linked to an elevated risk of lung cancer via multiple routes. These chemicals can be chemically converted into hazardous intermediate molecules, resulting in DNA damage and genetic alterations. VOCs can also cause oxidative stress, inflammation, and a breakdown in the cellular protective antioxidant framework, all of which contribute to the growth of lung cancer. Moreover, VOCs have been reported to alter critical biological reactions such as cell growth, apoptosis, and angiogenesis, leading to tumor development and metastasis. Epidemiological investigations have found a link between certain VOCs and a higher probability of LCs. Benzene, formaldehyde, and polycyclic aromatic hydrocarbons (PAHs) are some of the most well-researched VOCs, with comprehensive data confirming their cancer-causing potential. Nevertheless, the possible health concerns linked with many more VOCs and their combined use remain unknown, necessitating further research. Identifying the toxicological consequences of VOCs in LCs is critical for establishing focused preventative tactics and therapeutic strategies. Better legislation and monitoring mechanisms can limit VOC contamination in occupational and environmental contexts, possibly reducing the prevalence of LCs. Developing VOC exposure indicators and analyzing their associations with genetic susceptibility characteristics may also aid in early identification and targeted therapies.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Neoplasias Pulmonares , Compostos Orgânicos Voláteis , Humanos , Compostos Orgânicos Voláteis/efeitos adversos , Compostos Orgânicos Voláteis/análise , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Poluição do Ar em Ambientes Fechados/efeitos adversos , Poluição do Ar em Ambientes Fechados/análise
8.
Artigo em Inglês | MEDLINE | ID: mdl-37183464

RESUMO

BACKGROUND: In the last few decades, it has been largely perceived that the factors affecting the immune system and its varying pathways lead to the pathological progression of inflammation and inflammatory conditions. Chronic inflammation also contributes to common diseases, such as diabetes mellitus, ischemic heart disease, cancer, chronic renal inflammatory disease, non-alcoholic fatty hepat-ic disease, autoimmune diseases and neurodegenerative diseases. OBJECTIVE: Interestingly, plant sources and secondary metabolites from plants have been increasingly employed in managing acute and chronic inflammatory diseases for centuries. Boswellic acids are pentacyclic triterpenoidal moieties obtained from the oleo gum resin of different Boswellia species. METHODS: Detailed data was collected revealing the anti-inflammatory potential of Boswellic acids through various databases. RESULT: These are pharmacologically active agents that possess promising anti-inflammatory, anti-arthritic, antirheumatic, anti-diarrheal, anti-hyperlipidemic, anti-asthmatic, anti-cancer, and anti-microbial effects. CONCLUSION: Boswellic acids have been in use since ancient times primarily to treat acute and chronic inflammatory diseases. This review discusses the various mechanisms underlying the inflammatory process and the necessity of such natural products as a medication to treat inflammatory diseases. In addition, a discussion has also been extended to understand the primary targets involved in inflammation. The review further explores the therapeutic potential of boswellic acids in.


Assuntos
Anti-Inflamatórios , Extratos Vegetais , Humanos , Extratos Vegetais/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Inflamação/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Sistema Imunitário
9.
Eur J Pharmacol ; 962: 176234, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38043777

RESUMO

The study was performed to evaluate the neuroprotective effects of Benfotiamine (BFT) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) in rats. The rats were given daily doses of BFT (100 mg/kg, 200 mg/kg) through oral administration for 42 days. The rats were given a single bilateral dosage of MPTP (0.1 mg/nostril) intranasally once before the drug treatment to induce PD. On day 42, the animals were subjected to various behavioral paradigms. Post-treatment with BFT for 42 days significantly improved the motor and nonmotor fluctuations of MPTP. The results demonstrated that treatment with BFT ameliorated MPTP-induced disorders in behavior, body balance, and dopamine levels in the mid-brain. Among the post-treated groups, a high dose of BFT was the most effective treatment. Mean values are indicated in ±SEM, n = 5***(p < 0.001) when compared with the vehicle control, n = 5 ### (p < 0.001) when compared with the disease control; (p < 0.001) when compared with the BFT per se; (p < 0.001) when compared with the low dose of BFT; (p < 0.001) when compared with the high dose of BFT. Our finding suggests that BFT contributed to superior antioxidant, and anti-inflammatory and could be a novel therapeutic method for PD management. In conclusion, BFT could be a potential drug candidate for curbing and preventing PD.


Assuntos
Intoxicação por MPTP , Fármacos Neuroprotetores , Doença de Parkinson , Ratos , Animais , Camundongos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/etiologia , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Administração Oral , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Intoxicação por MPTP/tratamento farmacológico
10.
Artigo em Inglês | MEDLINE | ID: mdl-38037907

RESUMO

BACKGROUND: In the development of drug delivery systems, drugs' solubility remains the most challenging constraint. Many newly synthesized chemical compounds are available, but they involve low solubility and poor permeability restrictions. Among various drug delivery systems, the utilization of solid dispersion technologies has become more focused due to their promising benefits. OBJECTIVE: This technology has attracted extensive attention for dissolution rate improvement along with substantial bioavailability enhancement of poorly water-soluble drug candidates. METHODS: Many approaches have been employed for preparing solid dispersions, such as the melting method, hot melt extrusion, solvent evaporation process, fusion and kneading method, spray drying technique, co-grinding and freeze drying, supercritical fluid technology, etc. Result: A wide variety of hydrophilic and hydrophobic materials are available as carriers, which are employed in the formulation of solid dispersions. Depending on the carrier characteristics, immediate- release solid dispersions and/or controlled-release solid dispersions can be formulated. Multiple hydrophilic materials have been explored for heightening dissolution features with enhanced bioavailability of poorly water-soluble drug molecules. The availability of commercially available products further validates the utility of solid dispersion technology in drug delivery systems. CONCLUSION: In the current manuscript, an attempt has been made to highlight the comprehensive development techniques, characterization techniques, recent solid dispersion technologies, clinical trial studies, and patented technology, along with studies heightening the dissolution behavior of numerous poorly aqueous soluble drugs. The major stability issues affecting the suitability of solid dispersions are also discussed.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38078921

RESUMO

Asthma, lung cancer, cystic fibrosis, tuberculosis, acute respiratory distress syndrome, chronic obstructive pulmonary disease, and COVID-19 are few examples of inflammatory lung conditions that cause cytokine release syndrome. It can initiate a widespread inflammatory response and may activate several inflammatory pathways that cause multiple organ failures leading to increased number of deaths and increased prevalence rates around the world. Nanotechnology-based therapeutic modalities such as nanoparticles, liposomes, nanosuspension, monoclonal antibodies, and vaccines can be used in the effective treatment of inflammatory lung diseases at both cellular and molecular levels. This would also help significantly in the reduction of patient mortality. Therefore, nanotechnology could be a potent platform for repurposing current medications in the treatment of inflammatory lung diseases. The aim and approach of this article are to highlight the clinical manifestations of cytokine storm in inflammatory lung diseases along with the advances and potential applications of nanotechnology-based therapeutics in the management of cytokine storm. Further in-depth studies are required to understand the molecular pathophysiology, and how nanotechnology-based therapeutics can help to effectively combat this problem.

12.
Pathol Res Pract ; 252: 154908, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37950931

RESUMO

Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators of gene expression, contributing significantly to a diverse range of cellular processes, including apoptosis. One such lncRNA is NEAT1, which is elevated in several types of cancer and aid in cancer growth. However, recent studies have also demonstrated that the knockdown of NEAT1 can inhibit cancer cells proliferation, movement, and infiltration while enhancing apoptosis. This article explores the function of lncRNA NEAT1 knockdown in regulating apoptosis across multiple cancer types. We explore the existing understanding of NEAT1's involvement in the progression of malignant conditions, including its structure and functions. Additionally, we investigate the molecular mechanisms by which NEAT1 modulates the cell cycle, cellular proliferation, apoptosis, movement, and infiltration in diverse cancer types, including acute myeloid leukemia, breast cancer, cervical cancer, colorectal cancer, esophageal squamous cell carcinoma, glioma, non-small cell lung cancer, ovarian cancer, prostate cancer, and retinoblastoma. Furthermore, we review the recent studies investigating the therapeutic potential of NEAT1 knockdown in cancer treatment. Targeting the lncRNA NEAT1 presents a promising therapeutic approach for treating cancer. It has shown the ability to suppress cancer cell proliferation, migration, and invasion while promoting apoptosis in various cancer types.


Assuntos
Apoptose , Neoplasias , RNA Longo não Codificante , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Animais , Neoplasias/metabolismo
13.
J Chemother ; : 1-20, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37881008

RESUMO

This study aimed to optimize nanosuspension of sorafenib tosylate (an anticancer hydrophobic drug molecule) using a central composite design. Nanosuspension was prepared using a nanoprecipitation-ultrasonication approach. FTIR and DSC analyses demonstrated that the drug and excipients were physicochemically compatible. X-ray powder diffraction analysis confirmed amorphous form of the payload in the formulation. The optimized formulation (batch NSS6) had a zeta potential of -18.1 mV, a polydispersity of 0.302, and a particle size of 97.11 nm. SEM analysis confirmed formation of rod-shaped particles. After 24 h, about 64.45% and 86.37% of the sorafenib tosylate was released in pH 6.8 and pH 1.2, respectively. The MTT assay was performed on HepG2 cell lines. IC50 value of the optimized batch was 39.4 µg/mL. The study concluded that sorafenib tosylate nanosuspension could be a promising approach in the treatment of hepatocellular cancer.

14.
Int J Biol Macromol ; 253(Pt 7): 127375, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37839597

RESUMO

The intricate molecular pathways governing cancer development and progression have spurred intensive investigations into novel therapeutic targets. Glycogen Synthase Kinase-3 (GSK3), a complex serine/threonine kinase, has emerged as a key player with intricate roles in various cellular processes, including cell proliferation, differentiation, apoptosis, and metabolism. Harnessing GSK3 inhibitors as potential candidates for cancer therapy has garnered significant interest due to their ability to modulate key signalling pathways that drive oncogenesis. The review encompasses a thorough examination of the molecular mechanisms underlying GSK3's involvement in cancer progression, shedding light on its interaction with critical pathways such as Wnt/ß-catenin, PI3K/AKT, and NF-κB. Through these interactions, GSK3 exerts influence over tumour growth, invasion, angiogenesis, and metastasis, rendering it an attractive target for therapeutic intervention. The discussion includes preclinical and clinical studies, showcasing the inhibitors efficacy across a spectrum of cancer types, including pancreatic, ovarian, lung, and other malignancies. Insights from recent studies highlight the potential synergistic effects of combining GSK3 inhibitors with conventional chemotherapeutic agents or targeted therapies, opening avenues for innovative combinatorial approaches. This review provides a comprehensive overview of the current state of research surrounding GSK3 inhibitors as promising agents for cancer treatment.


Assuntos
Quinase 3 da Glicogênio Sintase , Neoplasias , Humanos , Quinase 3 da Glicogênio Sintase/metabolismo , Quinase 3 da Glicogênio Sintase/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , NF-kappa B/metabolismo
15.
Food Funct ; 14(18): 8101-8128, 2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37650738

RESUMO

The utilization of plant-derived supplements for disease prevention and treatment has long been recognized because of their remarkable potential. Ananas comosus, commonly known as pineapple, produces a group of enzymes called bromelain, which contains sulfhydryl moieties. Recent studies have shown that bromelain exhibits a wide range of activities, including anti-inflammatory, anti-diabetic, anti-cancer, and anti-rheumatic properties. These properties make bromelain a promising drug candidate for the treatment of various diseases. The anti-inflammatory activity of bromelain has been shown to be useful in treating inflammatory conditions such as osteoarthritis, rheumatoid arthritis, and asthma, whereas the anti-cancer activity of bromelain is via induction of apoptosis, inhibition of angiogenesis, and enhancement of the body's immune response. The anti-diabetic property of bromelain is owing to the improvement in glucose metabolism and reduction in insulin resistance. The therapeutic potential of bromelain has been investigated in numerous preclinical and clinical studies and a number of patents have been granted to date. Various formulations and delivery systems are being developed in order to improve the efficacy and safety of this molecule, including the microencapsulated form to treat oral inflammatory conditions and liposomal formulations to treat cancer. The development of novel drug delivery systems and formulations has further ameliorated the therapeutic potential of bromelain by improving its bioavailability and stability, while reducing the side effects. This review intends to discuss various properties and therapeutic applications of bromelain, along with its possible mechanism of action in treating various diseases. Recent patents and clinical trials concerning bromelain have also been covered.


Assuntos
Artrite Reumatoide , Asma , Humanos , Bromelaínas/farmacologia , Bromelaínas/uso terapêutico , Apoptose , Disponibilidade Biológica
16.
Curr Drug Deliv ; 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37519200

RESUMO

When breast cells divide and multiply out of control, it is called breast cancer. Symptoms include lump formation in the breast, a change in the texture or color of the breast, or a discharge from the nipple. Local or systemic therapy is frequently used to treat breast cancer. Surgical and radiation procedures limited to the affected area are examples of local management. There has been significant worldwide progress in the development of monoclonal antibodies (mAbs) since 1986, when the first therapeutic mAb, Orthoclone OKT3, became commercially available. mAbs can resist the expansion of cancer cells by inducing the destruction of cellular membranes, blocking immune system inhibitors, and preventing the formation of new blood vessels. mAbs can also target growth factor receptors. Understanding the molecular pathways involved in tumor growth and its microenvironment is crucial for developing effective targeted cancer therapeutics. Due to their unique properties, mAbs have a wide range of clinical applications. Antibody-drug conjugates (ADCs) are drugs that improve the therapeutic index by combining an antigen-specific antibody with a payload. This review focuses on the therapeutic applications, mechanistic insights, characteristics, safety aspects, and adverse events of mAbs like trastuzumab, bevacizumab, pertuzumab, ertumaxomab, and atezolizumab in breast cancer treatment. The creation of novel technologies utilizing modified antibodies, such as fragments, conjugates, and multispecific antibodies, must be a central focus of future studies. This review will help scientists working on developing mAbs to treat cancers more effectively.

17.
Curr Top Med Chem ; 23(21): 2001-2026, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37272462

RESUMO

BACKGROUND: Lung cancer is a highly lethal malignancy with a poor prognosis and the leading cause of mortality worldwide. The development of mutations makes lung cancer treatment more challenging and expensive. Successful identification of epidermal growth factor receptor (EGFR) mutations led to the discovery of various third-generation tyrosine kinase inhibitors. Osimertinib is one of the promising and efficacious third-generation EGFR inhibitors and is mainly employed in the treatment of non-small cell lung cancer. Despite the initial effective response, osimertinib causes resistance in most of the patients after around 10 months of therapy, resulting in disease progression. To mitigate the effect of developed resistance, different osimertinib derivatives have been synthesized and evaluated by numerous research groups across the globe. METHODS: Present article illustrates recent research advancements for the utilization of osimertinib and its derivatives in non-small cell lung cancer (NSCLC). Last seven years literature search has been conducted from PubMed, ScienceDirect, and Google Scholar databases, etc. Result: The present review emphasizes the recent advancements of osimertinib analogues that lead to enhanced antitumor potential and safety profile against non-small cell lung cancer. This manuscript also summarizes the different synthetic schemes involved in the synthesis of osimertinib analogues against EGFR reported by different research groups. CONCLUSION: Anticancer mechanistic insights, analytical prospects, drug interactions, pharmacokinetic considerations, and resistance profile of osimertinib are highlighted in the current manuscript.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Mutação , Receptores ErbB
18.
Pharm Nanotechnol ; 11(5): 410-424, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37157203

RESUMO

Nanotechnology suggests different innovative solutions to augment the worth of cosmetic products through the targeted delivery of content that manifests scientific innovation in research and development. Different nanosystems, like liposomes, niosomes, microemulsions, solid lipid nanoparticles, nanoform lipid carriers, nanoemulsions, and nanospheres, are employed in cosmetics. These nanosystems exhibit various innovative cosmetic functions, including site-specific targeting, controlled content release, more stability, improved skin penetration and enhanced entrapment efficiency of loaded compounds. Thus, cosmeceuticals are assumed as the highest-progressing fragment of the personal care industries that have progressed drastically over the years. In recent decades, cosmetic science has widened the origin of its application in different fields. Nanosystems in cosmetics are beneficial in treating different conditions like hyperpigmentation, wrinkles, dandruff, photoaging and hair damage. This review highlights the different nanosystems used in cosmetics for the targeted delivery of loaded content and commercially available formulations. Moreover, this review article has delineated different patented nanocosmetic formulation nanosystems and future aspects of nanocarriers in cosmetics.


Assuntos
Cosmecêuticos , Cosméticos , Cosmecêuticos/metabolismo , Pele/metabolismo , Cosméticos/metabolismo , Absorção Cutânea , Nanotecnologia
19.
Int J Surg ; 109(8): 2365-2377, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37158143

RESUMO

Wounds represent various significant health concerns for patients and also contribute major costs to healthcare systems. Wound healing comprises of overlapped and various coordinated steps such as homeostasis, inflammation, proliferation, and remodeling. In response to the failure of many strategies in delivering intended results including wound closure, fluid loss control, and exhibiting properties such as durability, targeted delivery, accelerated action, along with histocompatibility, numerous nanotechnological advances have been introduced. To understand the magnitude of wound therapy, this systematic and updated review discussing the effectiveness of nanoemulsions has been undertaken. This review portrays mechanisms associated with wound healing, factors for delayed wound healing, and various technologies utilized to treat wounds effectively. While many strategies are available, nanoemulsions have attracted the tremendous attention of scientists globally for the research in wound therapy due to their long-term thermodynamic stability and bioavailability. Nanoemulsions not only aid in tissue repair, but are also considered as an excellent delivery system for various synthetic and natural actives. Nanotechnology provides several pivotal benefits in wound healing, including improved skin permeation, controlled release, and stimulation of fibroblast cell proliferation. The significant role of nanoemulsions in improved wound healing along with their preparation techniques has also been highlighted with special emphasis on mechanistic insights. This article illustrates recent research advancements for the utilization of nanoemulsions in wound treatment. An adequate literature search has been conducted using the keywords 'Nanoemulsions in wound healing', 'Wound therapy and nanoemulsions', 'Herbal actives in wound therapy', 'Natural oils and wounds treatment' etc., from PubMed, Science Direct, and Google Scholar databases. Referred and original publications in the English language accessed till April 2022 has been included, whereas nonEnglish language papers, unpublished data, and nonoriginal papers were excluded from the study.


Assuntos
Atenção à Saúde , Cicatrização , Humanos
20.
Int J Biol Macromol ; 242(Pt 2): 124919, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37196717

RESUMO

Biocompatible magnetic nanoparticles are used for various biomedical applications. This study reported the development of nanoparticles with magnetic properties by embedding magnetite particles in the drug-loaded, crosslinked matrix of chitosan. Sorafenib tosylate-loaded magnetic nanoparticles were prepared by a modified ionic-gelation method. Particle size, zeta potential, polydispersity index, and entrapment efficiency of nanoparticles were in the range of 95.6 ± 3.4 nm to 440.9 ± 7.3 nm, 12.8 ± 0.8 mV to 27.3 ± 1.1 mV, 0.289 ± 0.011 to 0.571 ± 0.011, and 54.36 ± 1.26 % to 79.67 ± 1.40 %, respectively. The XRD spectrum of formulation CMP-5 confirmed the amorphous nature of the loaded drug in nanoparticles. TEM image confirmed the spherical shape of nanoparticles. Atomic force microscopic image of formulation CMP-5 indicated a mean surface roughness of 10.3597 nm. The magnetization saturation of formulation CMP-5 was 24.74 emu/g. Electron paramagnetic resonance spectroscopy revealed that formulation CMP-5's g-Lande's factor was 4.27, which was extremely near to the 4.30 (usual for Fe3+ ions). Residual paramagnetic Fe3+ ions may be responsible for paramagnetic origin. The data suggests superparamagnetic nature of particles. Formulations released 28.66 ± 1.22 % to 53.24 ± 1.95 % and 70.13 ± 1.72 % to 92.48 ± 1.32 % of the loaded drug after 24 h in pH 6.8 and pH 1.2, respectively. The IC50 value of formulation CMP-5 was 54.75 µg/mL in HepG2 (human hepatocellular carcinoma cell lines).


Assuntos
Quitosana , Nanopartículas de Magnetita , Nanopartículas , Humanos , Sorafenibe , Quitosana/química , Nanopartículas/química , Óxido Ferroso-Férrico , Microscopia de Força Atômica , Tamanho da Partícula , Portadores de Fármacos/química
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