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The superiority of nanomedicine over conventional medicines in the treatment of cancer has gained immediate recognition worldwide. As traditional cancer therapies are nonspecific and detrimental to healthy cells, the ability of nanomedicine to release drugs to target tumor cells specifically instead of healthy cells has brought new hope to cancer patients. This review focuses on the effects of various factors of nanoparticles such as transport, concentration in cells, tumor microenvironment, interaction with protein, penetration, uptake by tumor cells, cancer cell mutations, and intracellular trafficking of the nanoparticle. Besides the history of nanomedicine, future perspectives of nanomedicines are also explored in this text.
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Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Nanomedicina/métodos , Nanopartículas/administração & dosagem , Neoplasias/tratamento farmacológico , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Humanos , Nanopartículas/química , Nanopartículas/metabolismo , Neoplasias/metabolismo , Microambiente Tumoral/fisiologiaRESUMO
The hydrophobicity of bioactive molecules poses a considerable problem in the pharmaceutical and the food industry. Using food-based protein nanocarriers is one promising way to deliver hydrophobic molecules. These types of protein possess many functional properties such as surface activity, water-binding capacity, emulsification, foaming, gelation, and antioxidant activity, as well as their incorporation in the food industry as ingredients. Besides, they express low toxicity, are less expensive compared to synthetic polymers, and are biodegradable. This review aims to give a brief overview of the recent studies done using food proteins as colloidal delivery systems for hydrophobic and poorly soluble compounds.
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Proteínas Alimentares/administração & dosagem , Proteínas Alimentares/química , Sistemas de Liberação de Medicamentos/métodos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Nanopartículas/administração & dosagem , Nanopartículas/química , Animais , Sistemas de Liberação de Medicamentos/tendências , Géis , Humanos , Polímeros/administração & dosagem , Polímeros/química , Solubilidade , ÁguaRESUMO
Tyrosinase plays an important role in melanin biosynthesis and protects skin against ultraviolet radiations. Functional deficiency of tyrosinase results in serious dermatological diseases. Tyrosinase also participates in neuromelanin formation in the human brain, which leads to neurodegeneration resulting in Parkinson's disease. In fruits and vegetables, tyrosinase plays a critical role in senescence, causing undesired browning that results in faster deterioration and shorter shelf lines. The only commercially available tyrosinase is mushroom tyrosinase and it shows the highest homology to the mammalian tyrosinase. Although kojic acid is currently used as a tyrosinase inhibitor, they have serious side effects such as dermatitis, carcinogenesis and hepatotoxicity. Therefore, in order to develop a more active and safer tyrosinase inhibitor, 3D QSAR pharmacophore models were generated based on experimentally known inhibitors. The pharmacophore model, Hypo1, was developed with a large cost difference, high correlation coefficient and low RMS deviation. Hypo1 showed a good spatial arrangement; consisting of five-point features including two hydrogen bond acceptor, one hydrogen bond donor and two hydrophobic features. Hypo1 was further validated by cost analysis, test set and Fisher's randomisation method. Hypo1 was used as a 3D query for screening the in-house drug-like databases, and the hits were further selected by applying ADMET, Lipinski's rule of five and fit value criteria. To identify binding conformations, the obtained hits were subjected to molecular docking. Finally, molecular dynamics simulations revealed the appropriate binding modes of hit compounds. To conclude, we propose the final three hit compounds with new structural scaffolds as a virtual candidate as tyrosinase inhibitors.Communicated by Ramaswamy H. Sarma.
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Monofenol Mono-Oxigenase , Inibidores de Proteínas Quinases/química , Relação Quantitativa Estrutura-Atividade , Humanos , Ligação de Hidrogênio , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Monofenol Mono-Oxigenase/antagonistas & inibidoresRESUMO
Aptamers are small, functional single-stranded DNA or RNA oligonucleotides that bind to their targets with high affinity and specificity. Experimentally, aptamers are selected by the systematic evolution of ligands by exponential enrichment (SELEX) method. Here, we have used rational drug designing and bioinformatics methods to design the aptamers, which involves three different steps. First, finding a probable aptamer-binding site, and second, designing the recognition and structural parts of the aptamers by generating a virtual library of sequences, selection of specific sequence via molecular docking, molecular dynamics (MD) simulation, binding energy calculations, and finally evaluating the experimental affinity. Following this strategy, a 16-mer DNA aptamer was designed for Annexin A1 (ANXA1). In a direct binding assay, DNA1 aptamer bound to the ANXA1 with dissociation constants value of 83 nM. Flow cytometry and fluorescence microscopy results also showed that DNA1 aptamer binds specifically to A549, HepG2, U-87 MG cancer cells that overexpress ANXA1 protein, but not to MCF7 and L-02, which are ANXA1 negative cells. We further developed a novel system by conjugating DNA1 aptamer with doxorubicin and its efficacy was studied by cellular uptake and cell viability assay. Also, anti-tumor analysis showed that conjugation of doxorubicin with aptamer significantly enhances targeted therapy against tumors while minimizing overall adverse effects on mice health.
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Surgery is considered to be the favored approach for the treatment of most solid tumor malignancies. The quality of life among cancer patients has significantly improved due to advancements in instrumentation and surgical techniques; however, the recurrence of tumors and metastasis after operation remains challenging and results in a decreased quality of life and an increase in the mortality rate. Therefore, there is a need to explore applicable approaches to eradicate the circulating tumor cells and any residual tumor at the surgical site to inhibit the recurrence of the tumor and reduce the threat of distant metastasis. Recently drug delivery systems have been used to deliver immunotherapy or chemotherapy agents, which could augment the efficacy of surgical resection. In this review, we have summarized the efficacy and the recent progress of controlled drug delivery systems based approaches for post-surgical cancer treatment. Clinical translation challenges and opportunities have also been discussed.
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Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Neoplasias/tratamento farmacológico , Animais , Humanos , Hidrogéis/química , Micelas , Nanofibras/químicaRESUMO
Mesoporous silica nanomaterials (MSNs) have made remarkable achievements and are being thought of by researchers as materials that can be used to effect great change in cancer therapies, gene delivery, and drug delivery because of their optically transparent properties, flexible size, functional surface, low toxicity profile, and very good drug loading competence. Mesoporous silica nanoparticles (MSNPs) show a very high loading capacity for therapeutic agents. It is well known that cancer is one of the most severe known medical conditions, characterized by cells that grow and spread rapidly. Thus, curtailing cancer is one of the greatest current challenges for scientists. Nanotechnology is an evolving field of study, encompassing medicine, engineering, and science, and it has evolved over the years with respect to cancer therapy. This review outlines the applications of mesoporous nanomaterials in the field of cancer theranostics, as well as drug and gene delivery. MSNs employed as therapeutic agents, as well as their importance and future prospects in the ensuing generation of cancer theranostics and drug and therapeutic gene delivery, are discussed herein. Thus, the use of mesoporous silica nanomaterials can be seen as using one stone to kill three birds.
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Carbon dots are a carbonaceous nanomaterial that were discovered accidentally and are now drawing significant attention as a new quantum-sized fluorescent nanoparticle. Carbon dots are biocompatible, non-toxic, photostable, and easily functionalized with good photoluminescence and water solubility. Due to these unique properties, they are used broadly in live cell imaging, catalysis, electronics, biosensing, power, targeted drug delivery, and other biomedical applications. Here, we review the recent development of carbon dots in nanomedicine from their use in drug carriers to imaging agents to multifunctional theranostic systems. Finally, we discuss the challenges and views on next-generation carbon dot-based theranostics for clinical applications.
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Carbono/uso terapêutico , Nanoestruturas/uso terapêutico , Nanomedicina Teranóstica , Animais , Biomarcadores/metabolismo , Membrana Celular/metabolismo , Citoplasma/metabolismo , Diagnóstico por Imagem , Humanos , Neoplasias/diagnóstico , Neoplasias/terapiaRESUMO
Cisplatin cis-(diammine)dichloridoplatinum(II) (CDDP) is the first platinum-based complex approved by the food and drug administration (FDA) of the United States (US). Cisplatin is the first line chemotherapeutic agent used alone or combined with radiations or other anti-cancer agents for a broad range of cancers such as lung, head and neck. Aroplatin™, Lipoplatin™ and SPI-077 are PEGylated liposome-based nano-formulations that are still under clinical trials. They have many limitations, for example, poor aqueous solubility, drug resistance and toxicities, which can be overcome by encapsulating the cisplatin in Nemours nanocarriers. The extensive literature from different electronic databases covers the different nano-delivery systems that are developed for cisplatin. This review critically emphasizes on the recent advancement, development, innovations and updated literature reported for different carrier systems for CDDP.
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Cisplatino/química , Portadores de Fármacos/química , Nanomedicina/métodos , Nanoestruturas/química , Neoplasias/tratamento farmacológico , Animais , Cisplatino/uso terapêutico , HumanosRESUMO
For cancer therapy, the usefulness of mesoporous silica nanoparticles (MPSNPs) has been widely discussed, likely due to its inorganic nature and excellent structural features. The MPSNPs-based chemotherapeutics have been promisingly delivered to their target sites that help to minimize side effects and improve therapeutic effectiveness. A wide array of studies have been conducted to functionalize drug-loaded MPSNPs using targeting ligands and stimuli-sensitive substances. In addition, anticancer drugs have been precisely delivered to their target sites using MPSNPs, which respond to multi-stimuli. Furthermore, MPSNPs have been extensively tested for their safety and compatibility. The toxicity level of MPSNPs is substantially lower as compared to that of colloidal silica; however, in oxidative stress, they exhibit cytotoxic features. The biocompatibility of MPSNPs can be improved by modifying their surfaces. This article describes the production procedures, functionalization, and applications of biocompatible MPSNPs in drug delivery.
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Preparações de Ação Retardada/química , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Dióxido de Silício/química , Animais , Humanos , Nanomedicina Teranóstica/métodosRESUMO
BACKGROUND: Disulfiram (DSF) has a long history of being used as a first-line promising therapy for treatment of alcoholism in human. Besides its prominence in the treatment of alcoholism, extensive investigations have been carried out to explore other biomedical and pharmacological effects of DSF. Amongst other biomedical implications, plenty researches have shown evidence of promising anticancer efficacy of this agent for treatment of wide range of cancers such as breast cancer, liver cancer and lung carcinoma. METHODS: Electronic databases, including Google scholar, PubMed and Web of science were searched with the keywords disulfiram, nanoparticles, cancer, drug delivery systems. RESULT: Despite its excellent anticancer efficacy, the pharmaceutical significance and clinical applicability of DSF are hampered due to poor stability, low solubility, short plasma half-life, rapid metabolism, and early clearance from systemic circulation. Various attempts have been made to eradicate these issues. Nanotechnology based interventions have gained remarkable recognition in improving pharmacokinetic and pharmacodynamic profile of DSF by improving its stability and avoiding its degradation. CONCLUSION: The aim of the present review is to critically analyse all recent developments in designing various nanotechnology-based delivery systems, to ponder their relevance in improving stability, pharmacokinetic and pharmacodynamic profile, and achieving target-specific delivery of this agent to cancer cells to effectively eradicate cancer and abolish its metastasis. Nanotechnology is a novel approach for overcoming such obstacles faced presently, the results obtained so far using different novel drug delivery systems seem to be very promising to increase the stability and half-life of DSF. Graphical abstract Nanocrrier mediated drug delivery systems for disulfiram.
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Antineoplásicos/administração & dosagem , Dissulfiram/administração & dosagem , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Dissulfiram/química , Dissulfiram/farmacocinética , Portadores de Fármacos , Meia-Vida , Humanos , Nanopartículas , SolubilidadeRESUMO
Hydrogels evolved as an outstanding carrier material for local and controlled drug delivery that tend to overcome the shortcomings of old conventional dosage forms for small drugs (NSAIDS) and large peptides and proteins. The aqueous swellable and crosslinked polymeric network structure of hydrogels is composed of various natural, synthetic and semisynthetic biodegradable polymers. Hydrogels have remarkable properties of functionality, reversibility, sterilizability, and biocompatibility. All these dynamic properties of hydrogels have increased the interest in their use as a carrier for peptides and proteins to be released slowly in a sustained manner. Peptide and proteins are remarkable therapeutic agents in today's world that allow the treatment of severe, chronic and life-threatening diseases, such as diabetes, rheumatoid arthritis, hepatitis. Despite few limitations, hydrogels provide fine tuning of proteins and peptides delivery with enormous impact in clinical medicine. Novels drug delivery systems composed of smart peptides and molecules have the ability to drive self-assembly and form hydrogels at physiological pH. These hydrogels are significantly important for biological and medical fields. The primary objective of this article is to review current issues concerned with the therapeutic peptides and proteins and impact of remarkable properties of hydrogels on these therapeutic agents. Different routes for pharmaceutical peptides and proteins and superiority over other drugs candidates are presented. Recent advances based on various approaches like self-assembly of peptides and small molecules to form novel hydrogels are also discussed. The article will also review the literature concerning the classification of hydrogels on a different basis, polymers used, "release mechanisms" their physical and chemical characteristics and diverse applications.
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Abstract The modern process of new drug discovery and development is an exciting, yet a challenging, endeavor. Although it can result in significant financial income and meet the medical needs of patients, it ultimately may result in failure. To achieve a fast and successful new product discovery and development process, natural products which are evolutionarily optimized as drug-like molecules have gained great attention as better potential sources of new chemical entities. Historically, plant species containing berberine are used in various traditional phytotherapy. However, despite the various therapeutic effects it exerts, berberine is not yet developed into a drug product. Addressing the barriers that hinder its successful development and the efforts made to overcome them is thus crucial. The toxicological and pharmacokinetic properties of berberine are the main barriers towards its development into a marketed drug product. It has low aqueous solubility, poor absorption, fast metabolism, and wide tissue distribution which lead to low bioavailability limiting its clinical application. Synthetic berberine derivatives with improved properties are suggested as better alternatives for further development and future therapeutic application. Hence, this paper summarizes the preclinical research studies conducted in the last decade to reveal the therapeutic potential of synthetic berberine derivatives for the treatment of various diseases and hence achieve successful berberine-based drug development in the future. To exploit the value of natural products as a source of leads for the development of effective drugs, collaboration among the different discovery and development scientists is essential.