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Novel Routes to Accessing the Brain: Intranasal Administration
Published in Carla Vitorino, Andreia Jorge, Alberto Pais, Nanoparticles for Brain Drug Delivery, 2021
Ana Serralheiro, Joana Bicker, Gilberto Alves, Amílcar Falcäo, Ana Fortuna
It is important to consider the different methodologies used in intranasal studies since several experimental aspects such as delivery volume, administration technique, drug formulation and anaesthesia can all influence the distribution and deposition of drugs in the nasal cavity and, consequently, the pathways by which a drug may travel to the CNS after intranasal administration. The deposition of the drug within the nasal chamber should be appropriately optimised for the intended therapeutic goal, whether it may be highly concentrated at the olfactory mucosa for a CNS effect or low-deposited in that area when a systemic outcome is desired. Actually, the distance from the nostril to the olfactory epithelium is very short; however, its location in the slit-like olfactory cleft behind the narrow nasal vestibule and at the end of a complex labyrinth of respiratory turbinates severely complicates the access [2]. Expectably, deposition in adequate innervated regions of the nasal cavity can therefore be a critical component of the overall approach towards realising the full potential of nose-to-brain drug delivery [2].
Prevention and Treatment of Alzheimer’s Disease in the Light of Ayurveda
Published in Atanu Bhattacharjee, Akula Ramakrishna, Magisetty Obulesu, Phytomedicine and Alzheimer’s Disease, 2020
Vinayak Majhi, Bishnu Choudhury, Sudip Paul
Ayurveda has some novel methods of administering herbs, or their preparations, for treating CNS disorders. One novel method of herbal drug delivery, called “Nasya”, involves intranasal delivery of dry herbal powders or medicated oils. This is a practical, non-invasive, rapid, and simple method to deliver the therapeutic agents into the CNS. The use of medicated oils for Nasya require that the herbs be cooked in four parts oil and 16 parts water over a low flame until all of the water evaporates. This ensures the transport of lipophilic and lipid-soluble molecules across the Blood–Brain Barrier (BBB) membrane, where hydrophilic compounds exhibit minimal permeation. Intranasal administration offers numerous benefits for drug delivery into the CNS, and interest in this non-invasive route of administration has increased. The delivery is rapid, bypasses the BBB, and directly targets the CNS, thereby reducing systemic exposure and subsequent side effects (Rao et al. 2012).
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
Nasal drug delivery provides many advantages for administration of therapeutically active drugs for both small and large molecules. The high vascularity and immediate contact of drugs with the membrane for absorption promotes rapid response drugs for treating diseases such as migraines and as a route for emergency rescue therapies. Absorption bypassing the GI tract and liver make it a viable route for drugs that undergo high first-pass metabolism and proteins and peptides. In addition, the olfactory neuroepithelium provides pathways for direct nose-to-brain drug delivery, overcoming the barriers associated with the BBB. Although there are many advantages to nasal drug delivery, there are also many challenges. The variability in nasal cavity anatomy, relatively rapid clearance, volume limitation, and enzymatic activity of the nasal mucosa can limit the success of nasal drug delivery and provide opportunities for formulation and device technologies. Several formulation strategies for overcoming the barriers associated with nasal drug delivery have been used successfully for local, systemic, and CNS delivery of small molecules and proteins/peptides. These strategies continue to be investigated, with exploration of new avenues to safely improve drug efficacy after intranasal administration. As knowledge about particle deposition, anatomic structure, and absorption mechanisms in the nasal cavity expands, novel devices continue to be developed to deliver drug formulations to their intended target and maximize their intended purpose.
Auditory brainstem response testing using intranasal dexmedetomidine sedation in children: a pilot study
Published in International Journal of Audiology, 2021
Joanna Godbehere, Samuel Harper, Teresa Loxey, Christine Kirton, Rohit Verma, Simon Carr
Dexmedetomidine is a hypnotic drug used for paediatric sedation in non-painful procedures, it acts as a highly selective alpha-2 adrenergic agonist with a relatively short half-life of 2–3 h (Mason et al. 2013; Weerink et al. 2017; Reynolds and Sedillo 2018). Dosing is relatively safe due to the drug avoiding first-pass hepatic metabolism via the intranasal delivery route which in turn leads to slower absorption of the drug (Reynolds and Sedillo 2018). Intranasal administration also negates the need for IV insertion, which can be problematic in a non-cooperative child and often underpins much of the stress associated with paediatric anaesthesia (Reynolds and Sedillo 2018). The rationale for the choice of dexmedetomidine as opposed to oral chloral hydrate, midazolam, ketamine, midazolam, melatonin or rectal pentobarbitone was its strong safety profile, including lack of respiratory depression deeming it much safer to use in a ward rather than theatre setting compared to many other sedative agents (Reynolds and Sedillo 2018; Li et al. 2018; Mataftsi et al. 2017; Nordt et al. 2014; Isik, Baygin, and Bodur 2008).
Management of epileptic disorders using nanotechnology-based strategies for nose-to-brain drug delivery
Published in Expert Opinion on Drug Delivery, 2021
Mihika Shringarpure, Sankalp Gharat, Munira Momin, Abdelwahab Omri
In conjunction with the formulation development process, the designing of a correct container and closure system is critical. This parameter can impact the buildup of formulation inside the nasal cavity after intranasal administration. Another important considerations such as position of the head, volume of delivery and mode of administration should also be accounted for. It has been established that different head positions can modify the administration of formulation into the CNS [6]. In order to achieve maximum concentration into the CSF and olfactory bulb following intranasal delivery, the buildup of formulation into the esophagus and trachea must be an important consideration. The most favorable posture for brain targeting is when the patient’s head is down and in a forward position; though, this posture can result in compliance issues since it can be uncomfortable and inconvenient for the patient [80]. Tian et al. performed a comprehensive numerical analysis on airflow pattern and nanoparticle flux in human nasal cavity and olfactory region, where key factors contributing to olfactory deposition at low to moderate breathing rates were investigated [81].
Repurposing ibuprofen-loaded microemulsion for the management of Alzheimer’s disease: evidence of potential intranasal brain targeting
Published in Drug Delivery, 2021
Ming Ming Wen, Noha Ismail Khamis Ismail, Maha M. A. Nasra, Amal Hassan El-Kamel
Although ibuprofen had been on the market for a long time, it had not been tested through intranasal administration for brain targeting. In this study, the selected ibuprofen ME formulation (F1) demonstrated constant colloidal dispersion properties, appropriate drug release, and excellent stability upon exposure to various stressful stability tests. The promising nasal mucosal permeation and suitable viscosity of F1 allowed more amount of ibuprofen to reach the brain through the olfactory pathway. In vivo animal study further showed higher drug concentration reaching the brain through intranasal administration compared to intravenous and oral routes. The studied formulation F1 assured safety for intranasal administration with no nasal ciliotoxicity compared to the positive and negative control, and blank formulation. To reduce mucociliary clearance when dosing repeated regularly in the nose, many strategies could be applied in further studies, such as the incorporation of bioadhesive carrier, adjustment of the viscosity of the formulation, and using an application of a novel administration device. The present study demonstrated a great repurposing potential using ME as a dosage form to deliver ibuprofen for brain targeting through intranasal administration for the management of Alzheimer’s disease.