Trends in peptide drug discovery

Nature Reviews Drug Discovery, Journal Year: 2021, Volume and Issue: 20(4), P. 309 - 325

Published: Feb. 3, 2021

Language: Английский

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The evolution of commercial drug delivery technologies

Nature Biomedical Engineering, Journal Year: 2021, Volume and Issue: 5(9), P. 951 - 967

Published: April 1, 2021

Language: Английский

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G protein-coupled receptors: structure- and function-based drug discovery

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Jan. 8, 2021

Abstract As one of the most successful therapeutic target families, G protein-coupled receptors (GPCRs) have experienced a transformation from random ligand screening to knowledge-driven drug design. We are eye-witnessing tremendous progresses made recently in understanding their structure–function relationships that facilitated development at an unprecedented pace. This article intends provide comprehensive overview this important field broader readership shares some common interests discovery.

Language: Английский

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Smart nanoparticles for cancer therapy

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Nov. 3, 2023

Abstract Smart nanoparticles, which can respond to biological cues or be guided by them, are emerging as a promising drug delivery platform for precise cancer treatment. The field of oncology, nanotechnology, and biomedicine has witnessed rapid progress, leading innovative developments in smart nanoparticles safer more effective therapy. In this review, we will highlight recent advancements including polymeric dendrimers, micelles, liposomes, protein cell membrane mesoporous silica gold iron oxide quantum dots, carbon nanotubes, black phosphorus, MOF others. We focus on their classification, structures, synthesis, intelligent features. These possess the ability various external internal stimuli, such enzymes, pH, temperature, optics, magnetism, making them systems. Additionally, review explore latest studies tumor targeting functionalizing surfaces with tumor-specific ligands like antibodies, peptides, transferrin, folic acid. also summarize different types options, small molecules, proteins, nucleic acids, even living cells, potential use While is promising, acknowledge challenges clinical prospects associated use. Finally, propose blueprint that involves artificial intelligence-powered treatment applications. By harnessing aims usher new era personalized therapy, providing patients individualized options.

Language: Английский

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Peptides as a platform for targeted therapeutics for cancer: peptide–drug conjugates (PDCs)

Chemical Society Reviews, Journal Year: 2020, Volume and Issue: 50(3), P. 1480 - 1494

Published: Dec. 21, 2020

A tutorial review showcasing how peptide–drug conjugates can offer the versatility needed for a successful drug discovery approach, their problems and future opportunities.

Language: Английский

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GLP-1 physiology informs the pharmacotherapy of obesity

Molecular Metabolism, Journal Year: 2021, Volume and Issue: 57, P. 101351 - 101351

Published: Oct. 8, 2021

Glucagon-like peptide-1 receptor agonists (GLP1RA) augment glucose-dependent insulin release and reduce glucagon secretion gastric emptying, enabling their successful development for the treatment of type 2 diabetes (T2D). These agents also inhibit food intake body weight, fostering investigation GLP1RA obesity. Here I discuss physiology (GLP-1) action in control animals humans, highlighting importance gut vs. brain-derived GLP-1 feeding weight. The widespread distribution function multiple (GLP1R) populations central autonomic nervous system are outlined, pathways controlling energy expenditure preclinical studies reduction both humans is highlighted. relative contributions vagal afferent GLP1R+ physiological anorectic response to compared reviewed. Key data two obesity therapy (liraglutide 3 mg daily semaglutide 2.4 once weekly) discussed. Finally, emerging potentially supporting combination with additional peptide epitopes unimolecular multi-agonists, as well fixed-dose therapies, actions weight highly conserved obese adolescents adults. well-defined mechanisms through a single G protein-coupled receptor, together extensive safety database people T2D, provide reassurance surrounding long-term use these co-morbidities. may be effective conditions associated obesity, such cardiovascular disease non-alcoholic steatohepatitis (NASH). Progressive improvements efficacy suggest that GLP-1-based therapies soon rival bariatric surgery viable options its complications.

Language: Английский

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Oral delivery of therapeutic peptides and proteins: Technology landscape of lipid-based nanocarriers

Advanced Drug Delivery Reviews, Journal Year: 2022, Volume and Issue: 182, P. 114097 - 114097

Published: Jan. 7, 2022

The oral administration of therapeutic peptides and proteins is favoured from a patient commercial point view. In order to reach the systemic circulation after administration, these drugs have overcome numerous barriers including enzymatic, sulfhydryl, mucus epithelial barrier. development formulations for therefore necessary. Among most promising formulation approaches are lipid-based nanocarriers such as oil-in-water nanoemulsions, self-emulsifying drug delivery systems (SEDDS), solid lipid nanoparticles (SLN), nanostructured carriers (NLC), liposomes micelles. As lipophilic character can be tremendously increased by formation hydrophobic ion pairs (HIP) with counter ions, they incorporated in phase carriers. Since gastrointestinal (GI) peptidases well sulfhydryl compounds glutathione dietary too hydrophilic enter carriers, peptide or protein protected towards enzymatic degradation unintended thiol/disulfide exchange reactions. Stability lipases provided use excipients that not just poorly degraded enzymes. Nanocarriers size <200 nm mucoinert surface PEG zwitterionic surfaces exhibit high permeating properties. Having reached underlying absorption membrane, enable paracellular lymphatic uptake, induce endocytosis transcytosis simply fuse cell membrane releasing their payload into circulation. Numerous vivo studies provide evidence potential systems. Within this review we an overview about different delivery, highlight progress made on them discuss strengths weaknesses comparison other technologies.

Language: Английский

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Glucagon-like peptide-1 receptor co-agonists for treating metabolic disease

Molecular Metabolism, Journal Year: 2020, Volume and Issue: 46, P. 101090 - 101090

Published: Sept. 25, 2020

Glucagon-like peptide-1 receptor (GLP-1R) agonists are approved to treat type 2 diabetes and obesity. They elicit robust improvements in glycemic control weight loss, combined with cardioprotection individuals at risk of or pre-existing cardiovascular disease. These attributes make GLP-1 a preferred partner for next-generation therapies exhibiting improved efficacy yet retaining safety diabetes, obesity, non-alcoholic steatohepatitis, related cardiometabolic disorders. The available clinical data demonstrate that the best GLP-1R not competitive bariatric surgery, emphasizing need further improve current medical therapy. In this article, we discuss highlighting physiological pharmacological potential peptide non-peptide partners, exemplified by amylin, glucose-dependent insulinotropic polypeptide (GIP), steroid hormones. We review progress, limitations, future considerations translating findings from preclinical experiments humans Multiple co-agonist combinations exhibit promising efficacy, notably tirzepatide investigational amylin combinations. Simultaneously, increasing doses such as semaglutide produces substantial raising bar development new unimolecular co-agonists. Collectively, suggest co-agonists should prove superior alone metabolic

Language: Английский

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Oral delivery of proteins and peptides: Challenges, status quo and future perspectives

Acta Pharmaceutica Sinica B, Journal Year: 2021, Volume and Issue: 11(8), P. 2416 - 2448

Published: April 29, 2021

Proteins and peptides (PPs) have gradually become more attractive therapeutic molecules than small molecular drugs due to their high selectivity efficacy, but fewer side effects. Owing the poor stability limited permeability through gastrointestinal (GI) tract epithelia, PPs are usually administered by parenteral route. Given big demand for oral administration in clinical use, a variety of researches focused on developing new technologies overcome GI barriers PPs, such as enteric coating, enzyme inhibitors, permeation enhancers, nanoparticles, well intestinal microdevices. Some been developed under trials even market. This review summarizes history, physiological overcoming approaches, current preclinical technologies, future prospects delivery PPs.

Language: Английский

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Prebiotics‐Encapsulated Probiotic Spores Regulate Gut Microbiota and Suppress Colon Cancer

Advanced Materials, Journal Year: 2020, Volume and Issue: 32(45)

Published: Oct. 1, 2020

Abstract While microbial‐based therapy has been considered as an effective strategy for treating diseases such colon cancer, its safety remains the biggest challenge. Here, probiotics and prebiotics, which possess ideal biocompatibility are extensively used additives in food pharmaceutical products, combined to construct a safe microbiota‐modulating material. Through host–guest chemistry between commercial Clostridium butyricum chemically modified prebiotic dextran, prebiotics‐encapsulated probiotic spores (spores‐dex) prepared. It is found that spores‐dex can specifically enrich cancers after oral administration. In lesion, dextran fermented by C. , thereby produces anti‐cancer short‐chain fatty acids (SCFAs). Additionally, regulate gut microbiota, augment abundance of SCFA‐producing bacteria (e.g., Eubacterium Roseburia ), markedly increase overall richness microbiota. subcutaneous orthotopic tumor models, drug‐loaded inhibit growth up 89% 65%, respectively. Importantly, no obvious adverse effect found. The work sheds light on possibility using highly provides promising avenue various gastrointestinal diseases.

Language: Английский

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