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Fundamentals in nasal drug delivery
Published in Anthony J. Hickey, Heidi M. Mansour, Inhalation Aerosols, 2019
Zachary Warnken, Yu Jin Kim, Heidi M. Mansour, Robert O. Williams, Hugh D.C. Smyth
The nasal route is advantageous for the delivery of small molecules, proteins, and peptides to the CNS, and can be used for the treatment of acute pain, migraines, smoking (nicotine addiction), or various neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Once drugs are delivered into the nasal cavity and reach the cribriform plate, the substances can be delivered to the brain through the olfactory bulbs or trigeminal nerve (direct pathways) or through the lymphatic system (indirect pathway) (80). Although the direct pathway circumvents the BBB, drugs transported via the lymphatic system and drained into the circulation may enter the brain if the substances pass through the BBB (80). Multiple factors influence the transport of drug substances across the BBB. In general, lipophilic compounds with molecular weight less than 500 Da and low numbers of hydrogen bond donors and acceptors are favorable for passive diffusion (81). Absorption enhancers are commonly employed to improve the transport of hydrophilic macromolecules like proteins and peptides to target areas in the brain (79,82). The applications of PEGylated nanoparticles and colloidal nanocarrier systems such as liposomes, micelles, and emulsions to the nasal delivery of peptide therapeutics are other possible options (79,81,83). These strategies to improve the intranasal delivery of protein and peptide drugs are reviewed in the next section.
Sustainability and Future Choices for Societies
Published in Harry F. Tibbals, Medical Nanotechnology and Nanomedicine, 2017
Since the emergence of the biotechnology industry beginning in the 1970s, technology has been available to make a large number of entirely new pharmaceuticals. With the elucidation of the human genome, the targeting of diseases by biotechnology-engineered drugs has become accelerated and focused. And the availability of widespread and low-cost decoding of individual genomes has opened even more opportunities of targeted bioengineered therapeutics. Much research effort has been directed toward identifying and producing small molecule therapeutics, which could be delivered by traditional means. At first, peptide therapeutics, the most natural outcome of the biotechnology and genome revolution, had been accumulating on the shelf. But as nanomedicines provide effective protection and targeted release mechanisms, the huge backlog of biotechnology-generated peptide therapeutics is beginning to move toward clinical applications. This movement will have large health and economic impacts. It could hold the promise of defeat of intractable scourges such as malaria and cholera, with enormous economic consequences [47].
New and Emerging Therapies for Anxiety
Published in Siegfried Kasper, Johan A. den Boer, J. M. Ad Sitsen, Handbook of Depression and Anxiety, 2003
David J. Nutt, Spilios V. Argyropoulos
One of the more exciting areas of research in depression is the search for peptide therapeutics that will attack depression at its presumed source—the central and peripheral stress axis. Corticotropin-release factor (CRF) is one, if not the main, hormone-mediating stress in the brain. CRF production in the nervous system is increased by stress and if CRF is injected into the ventricles of animals it produces many of the behavioral effects of stress. For nearly a decade now, we have known that blocking central CRF receptors could reduce stress-related behavior in animals, although these experiments initially relied on directly injecting a peptide analog of CRF (α-helical CRF) or antisense to CRF directly into the brain [29]. More recently, stable small-molecule antagonists have been discovered and studies with these have confirmed that central CRF mediates many of the behavioral responses to stress in animals (for review, see Ref.20).
The industrial design, translation, and development strategies for long-acting peptide delivery
Published in Expert Opinion on Drug Delivery, 2022
Bin Yang, Ana Gomes Dos Santos, Sanyogitta Puri, Annette Bak, Liping Zhou
According to the Global Peptide Therapeutics Market & Clinical Pipeline Insight 2026 report published in January of 2020, peptides have emerged as one of the important classes of therapeutic molecules, being developed by various pharmaceutical and biotech companies in order to attain a targeted drug delivery for several ailments. Currently, there are 197 peptide-based drugs commercially available. Research into new peptide therapeutics continues at a steady speed, with more than 800 peptide drugs in clinical pipelines. Examples of approved peptide drugs and those in clinical trials have been recently reviewed [1–3]. The global peptide drug market is projected to surpass US$ 60 billion by year 2026 [4]. Peptide drugs have been developed in a wide range of pharmaceutical indications such as metabolic and cardiovascular diseases, endocrinology, urology, respiratory, pain, antimicrobial disease, and cancer [5].
Long-acting injectable formulation technologies: challenges and opportunities for the delivery of fragile molecules
Published in Expert Opinion on Drug Delivery, 2022
Andrea Gonella, Sylvestre Grizot, Fang Liu, Adolfo López Noriega, Joël Richard
The growing interest around the use of peptide therapeutics is well documented by the huge number of molecules in active clinical development, estimated to be around 170, covering a wide range of applications. Considering only approved molecules, areas such as urology, respiratory, and cardiovascular diseases, pain, oncology, metabolic disorders, and infections are most commonly associated to peptide drugs treatments [6]. Regarding protein therapeutics, monoclonal antibody-based therapies have had incredible success over the last decades, due to the high specificity and usually long half-life of these molecules. Monoclonal antibodies found many applications for indications such as cancer (e.g. Trastuzumab or Bevacizumab) or immune diseases (e.g. Adalimumab or Infliximab). However, many other protein therapeutics like hormones, cytokines, growth factors, and enzymes, were approved in the past and are currently used for the treatment of many diseases (e.g. multiple sclerosis, Gaucher’s disease or rheumatoid arthritis) [7,8].
How can we improve peptide drug discovery? Learning from the past
Published in Expert Opinion on Drug Discovery, 2021
Despite the current market successes, in the past the enthusiasm for peptides by the pharmaceutical industry has been somewhat muted by the difficulty in achieving oral bioavailability for peptides [8]. This lack of oral bioavailability is clearly apparent from the fact that the administration routes of currently approved peptide therapeutics are dominated by the subcutaneous (78%) and intravenous (13%) routes [6]. Other factors that have limited peptide market penetration include concerns about their potential manufacturing costs [9,10], short biological half-lives, and poor tissue penetration [11]. For clarity, we note that in this editorial we define peptides as comprising ~50 or fewer amino acids, and that we specifically focus on structurally constrained peptides for the rest of this article.