Novel Routes to Accessing the Brain: Intranasal Administration
Carla Vitorino, Andreia Jorge, Alberto Pais in Nanoparticles for Brain Drug Delivery, 2021
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
Atanu Bhattacharjee, Akula Ramakrishna, Magisetty Obulesu in Phytomedicine and Alzheimer’s Disease, 2020
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
Anthony J. Hickey, Heidi M. Mansour in Inhalation Aerosols, 2019
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.
Nasal residence time and rheological properties of a new bentonite-based thixotropic gel emulsion nasal spray – AM-301
Published in Drug Development and Industrial Pharmacy, 2023
Martin M. Sailer, Melanie Köllmer, Beatrice Masson, Fabio Fais, Ilja P. Hohenfeld, Michael E. Herbig, Assen K. Koitschev, Sven Becker
The main inclusion and exclusion criteria of the study were the following: Eight healthy male volunteers aged between 18 and 50 years and with a BMI between 18.0 and 25.0 kg/m2 were invited to participate in the study via a message through a study portal for clinical trials of the Eberhard-Karls University Tübingen. Subjects with a clinically relevant nasal obstruction or pathology precluding effective and/or efficient intranasal delivery (determined by nasal cavity endoscopy) were excluded. Other exclusion criteria were any nasal treatments within 30 days prior to study start (including nasal sprays, nasal drops and saline washes), any ongoing upper respiratory tract infection, rhinitis (symptomatic) or asthma, any clinically relevant medical history or concomitant medication, history of severe or abnormal drug reaction, known sensitivity to fluorescein or any constituents of AM-301, or concomitant or prior treatment with another investigational medicinal product or device within 30 days prior to the study start.
Comparative evaluation of intranasal midazolam, dexmedetomidine, ketamine for their sedative effect and to facilitate venous cannulation in pediatric patients: A prospective randomized study
Published in Egyptian Journal of Anaesthesia, 2022
Rasha Gamal Abusinna, Wael Sayed Algharabawy, Marwa Mostafa Mowafi
If a cannula is already inserted, intravenous induction is a safe, simple, and quick method of induction in pediatric patients. Many recent studies have found that intravenous induction is superior to inhalational induction [1,4,5]. Pediatric intravenous cannulation is technically challenging and may result in psychological issues. Children typically resist any attempts to approach them and make it difficult to insert a cannula for them. Furthermore, children always resist being separated from their parents in order to be taken to the operating room [1], [4]. Sedative premedications play an important role in pediatric anesthesia, helping patients overcome fear and anxiety associated with cannula insertion and making it easier for them to separate from their parents. There are many routes for administering sedatives that do not require the insertion of a venous line, such as oral, intranasal, intramuscular, and rectal. The intranasal approach is safe and painless, and children tolerate it well, with a comparable onset of action to the intravenous approach [1],[2],[4].
A sensitive and high-throughput LC-ESI-MS/MS method to detect budesonide in human plasma: application to an evaluation of pharmacokinetics of budesonide intranasal formulations with and without charcoal-block in healthy volunteers
Published in Drug Development and Industrial Pharmacy, 2021
Xin Li, Huan Tong, Bing Xu, Yang Deng, Yuan Li, Junchen Huang, Yong Mao, Mengqin Liu, Ping Zhang, Siwei Guo
Intranasal corticosteroids (INCs), usually administered as a locally acting nasal suspension spray, are considered first-line therapy for allergic rhinitis [1,2]. They exert a local anti-inflammatory effect mediated by intracellular activation of the glucocorticoid receptor (GR) after being absorbed across the nasal mucosa [3]. However, a large proportion of intranasally administered drugs might be quickly cleared into the gastrointestinal (GI) tract because of the small volume of the nasal cavity and the pushing of nose cilia [4,5]. Systemic exposure following intranasal administration results from drug absorption from the nasal mucosa, and GI tract by ingestion. Although systemic absorption may produce some clinical efficacy for certain corticosteroids, its consequences (e.g. the suppression of the hypothalamic-pituitary-adrenal axis) are generally unacceptable [6]. Therefore, systemic exposure is a valuable parameter for the safety of INC suspension products, and local exposure is considered to be direct evidence to evaluate the efficacy [7]. If GI absorption is avoided, the systemic exposure will be attributed entirely to the drug absorption from the nasal cavity. This could be achieved by co-administration with activated charcoal, which is usually used to prevent the absorption of the poison from the GI tract and also used to measure the local lung absorption and exposure of orally inhaled drug products [8].
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