Handbook of experimental pharmacology最新文献_第6页

Advanced Formulation Approaches for Emerging Therapeutic Technologies. 新兴治疗技术的先进配方方法。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2023_695

Nour Allahham, Ines Colic, Melissa L D Rayner, Pratik Gurnani, James B Phillips, Ahad A Rahim, Gareth R Williams

{"title":"Advanced Formulation Approaches for Emerging Therapeutic Technologies.","authors":"Nour Allahham, Ines Colic, Melissa L D Rayner, Pratik Gurnani, James B Phillips, Ahad A Rahim, Gareth R Williams","doi":"10.1007/164_2023_695","DOIUrl":"10.1007/164_2023_695","url":null,"abstract":"In addition to proteins, discussed in the Chapter \"Advances in Vaccine Adjuvants: Nanomaterials and Small Molecules\", there are a wide range of alternatives to small molecule active ingredients. Cells, extracellular vesicles, and nucleic acids in particular have attracted increasing research attention in recent years. There are now a number of products on the market based on these emerging technologies, the most famous of which are the mRNA-based vaccines against SARS-COV-2. These advanced therapeutic moieties are challenging to formulate however, and there remain significant challenges for their more widespread use. In this chapter, we consider the potential and bottlenecks for developing further medical products based on these systems. Cells, extracellular vesicles, and nucleic acids will be discussed in terms of their mechanism of action, the key requirements for translation, and how advanced formulation approaches can aid their future development. These points will be presented with selected examples from the literature, and with a focus on the formulations which have made the transition to clinical trials and clinical products.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"343-365"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41095475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Blood-Brain Barrier (BBB)-Crossing Strategies for Improved Treatment of CNS Disorders. 改善中枢神经系统疾病治疗的血脑屏障 (BBB) 穿越策略。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2023_689

Wandong Zhang

引用次数: 0

Pharmacology of Mammalian Na⁺-Dependent Transporters of Inorganic Phosphate. 哺乳动物无机磷酸盐 Na+ 依赖性转运体的药理学。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2022_633

Carsten A Wagner

{"title":"Pharmacology of Mammalian Na+-Dependent Transporters of Inorganic Phosphate.","authors":"Carsten A Wagner","doi":"10.1007/164_2022_633","DOIUrl":"10.1007/164_2022_633","url":null,"abstract":"Inorganic phosphate (Pi) is an essential component of many biologically important molecules such as DNA, RNA, ATP, phospholipids, or apatite. It is required for intracellular phosphorylation signaling events and acts as pH buffer in intra- and extracellular compartments. Intestinal absorption, uptake into cells, and renal reabsorption depend on a set of different phosphate transporters from the SLC20 (PiT transporters) and SLC34 (NaPi transporters) gene families. The physiological relevance of these transporters is evident from rare monogenic disorders in humans affecting SLC20A2 (Fahr's disease, basal ganglia calcification), SLC34A1 (idiopathic infantile hypercalcemia), SLC34A2 (pulmonary alveolar microlithiasis), and SLC34A3 (hereditary hypophosphatemic rickets with hypercalciuria). SLC34 transporters are inhibited by millimolar concentrations of phosphonoformic acid or arsenate while SLC20 are relatively resistant to these compounds. More recently, a series of more specific and potent drugs have been developed to target SLC34A2 to reduce intestinal Pi absorption and to inhibit SLC34A1 and/or SLC34A3 to increase renal Pi excretion in patients with renal disease and incipient hyperphosphatemia. Also, SLC20 inhibitors have been developed with the same intention. Some of these substances are currently undergoing preclinical and clinical testing. Tenapanor, a non-absorbable Na+/H+-exchanger isoform 3 inhibitor, reduces intestinal Pi absorption likely by indirectly acting on the paracellular pathway for Pi and has been tested in several phase III trials for reducing Pi overload in patients with renal insufficiency and dialysis.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"285-317"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10461035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Collaborative Innovations in Childhood Cancer Therapies. 儿童癌症疗法的合作创新。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2024_725

Iris Valtingojer, Sasha Lièvre, Philippe Bordes, Krupa Paranjpe, Winifred Thompson, Sachin Shah, Valeria Fantin, Wendy Jacquemet-Ross, Peter C Adamson

引用次数: 0

Progress in Ocular Drug Delivery: Challenges and Constraints. 眼部给药的进展：挑战与制约。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2023_693

Ilva D Rupenthal, Priyanka Agarwal

引用次数: 0

Advances in Vaccine Adjuvants: Nanomaterials and Small Molecules. 疫苗佐剂的进展：纳米材料和小分子。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2023_652

Bingbing Sun, Min Li, Zhiying Yao, Ge Yu, Yubin Ma

引用次数: 0

Signalling of Adrenoceptors: Canonical Pathways and New Paradigms. 肾上腺素受体的信号传导：经典途径和新范例。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2023_704

Chantel Mastos, Xiaomeng Xu, Alastair C Keen, Michelle L Halls

引用次数: 0

Adrenoceptors and Hypertension. 肾上腺素受体与高血压。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2024_719

Spoorthy Kulkarni, Ian B Wilkinson

{"title":"Adrenoceptors and Hypertension.","authors":"Spoorthy Kulkarni, Ian B Wilkinson","doi":"10.1007/164_2024_719","DOIUrl":"10.1007/164_2024_719","url":null,"abstract":"Hypertension is a very prevalent condition associated with high mortality and morbidity, secondary to changes resulting in blood vessels and resultant end-organ damage. Haemodynamic changes, including an initial rise in cardiac output followed by an increase in total peripheral resistance, denote the early changes associated with borderline or stage 1 hypertension, especially in young men. Increased sodium reabsorption leading to kidney damage is another mechanism proposed as one of the initial triggers for essential hypertension. The underlying pathophysiological mechanisms include catecholamine-induced α1- and ß1-adrenoceptor stimulation, and renin-angiotensin-aldosterone system activation leading to endothelial dysfunction which is believed to lead to persistent blood pressure elevation.α1 blockers, α2 agonists, and ß blockers were among the first oral anti-hypertensives. They are no longer first-line therapy after outcome trials did not demonstrate any benefits over and above other agents, despite similar blood pressure reductions. Angiotensin-converting enzyme inhibitors (or angiotensin receptor blockers), calcium channel blockers, and thiazide-like diuretics are now considered the first line of therapy, although adrenoceptor agents still have a role as second- or third-line therapy. The chapter also highlights hypertension in specific medical conditions such as pregnancy, phaeochromocytoma, hyperthyroidism, portal hypertension, pulmonary arterial hypertension, and ocular hypertension, to provide an overview for clinicians and researchers interested in the role of adrenoceptors in the pathophysiology and management of hypertension.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"297-332"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reaching Outer Space and Enabling the mRNA Revolution: A Critical Role of Partnerships for Successful Drug and Vaccine Development. 进入外层空间，推动 mRNA 革命：合作伙伴关系对成功开发药物和疫苗的关键作用》。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2024_723

Anita Seshire, Yukun Duan, Kahina Lang

{"title":"Reaching Outer Space and Enabling the mRNA Revolution: A Critical Role of Partnerships for Successful Drug and Vaccine Development.","authors":"Anita Seshire, Yukun Duan, Kahina Lang","doi":"10.1007/164_2024_723","DOIUrl":"10.1007/164_2024_723","url":null,"abstract":"mRNA and targeted delivery of mRNA carry the promise to enable targeted treatment of undruggable diseases with high unmet medical needs. The transient nature of mRNA opens options for safe influencing of protein biology, immune responses, and complex ailments without impacting DNA heritage. Technical challenges such as mRNA stability and targeted delivery require next generation solutions, which attracted substantial funding and research interests. To build an integrated mRNA value chain and enable the development of novel therapeutics, Merck KGaA Darmstadt, Germany has initiated an internally incubated program, \"Targeted mRNA Delivery\" (TMD). This collaborative approach brings together scientists, researchers, engineers, and commercial experts from diverse backgrounds to overcome the multidimensional challenges associated with mRNA technology. In this chapter, the multiple opportunities and challenges for the development of mRNA formulations and therapeutics are described comprehensively. Specifically, the TMD program is presented as a use case to show how intrapreneurs were gathered to establish internal mRNA capabilities and foster collaborations for technology development. In the realm of targeted mRNA delivery, partnerships, encompassing internal partnership and external private, public, and hybrid collaborations, play a crucial role in driving innovation and addressing these hurdles. Within multinational pharmaceutical companies, the establishment of \"internal startups\" is an effective solution to drive innovation to the next level with support from different business sectors, where existing capabilities and positioning are seamlessly blended with the agility and speed of a startup.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"51-81"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142284446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RNA Delivery to Mitochondria. 将 RNA 运送到线粒体。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2023_650

Yuma Yamada, Hideyoshi Harashima

{"title":"RNA Delivery to Mitochondria.","authors":"Yuma Yamada, Hideyoshi Harashima","doi":"10.1007/164_2023_650","DOIUrl":"10.1007/164_2023_650","url":null,"abstract":"The approval of mRNA-containing lipid nanoparticles (LNPs) for use in a vaccine against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the clinical utility of RNA-loaded nanocapsules has stimulated a rapid acceleration in research in this area. The development of mRNA-containing LNP vaccines has been rapid, not only because of regulatory adjustments, but also to the advances made in nucleic acid delivery as the result of efforts by many basic researchers. RNA functions, not only in the nucleus and cytoplasm, but also in mitochondria, which have their own genomic apparatus. Mitochondrial diseases caused by mutations or defects in the mitochondrial genome, mitochondrial DNA (mtDNA) are intractable and are mainly treated symptomatically, but gene therapy as a fundamental treatment is expected to soon be a reality. To realize this therapy, a drug delivery system (DDS) that delivers nucleic acids including RNA to mitochondria is required, but efforts in this area have been limited compared to research targeting the nucleus and cytoplasm. This contribution provides an overview of mitochondria-targeted gene therapy strategies and discusses studies that have attempted to validate mitochondria-targeted RNA delivery therapies. We also present the results of 'RNA delivery to mitochondria' based on the use of our mitochondria-targeted DDS (MITO-Porter) that was developed in our laboratory.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"329-339"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9302621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0