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Nasal delivery is an alternative to oral or parenteral administration due to certain limitations such as absorption of the drug, drug targeting to particular organs can cause a problem for administration through oral route. The nasal route has also been successfully used for bypassing the blood-brain barrier and afterword delivering drug molecules...
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Chronic wounds are a significant and growing health problem, and clinical treatment is often a painful experience. A topical dosage form would be optimal to treat this pain. Poloxamer 407, a thermosensitive polymer that is a liquid at low temperatures but gels at higher temperatures, is well suited to administer topical analgesics to chronic wound...
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... After being injected, in situ gelation happens at the body temperature of the nose. This is possible with the help of different thermosensitive polymers [6]. Poloxamer 407 is a thermosensitive polymer that is often used. ...
Background: Meclizine hydrochloride (MCZ) is an antihistamine that is used as an antiemetic to prevent and cure nausea and vomiting. Because of its limited water solubility and first-pass metabolism, it exhibits variable absorption. Objective: To formulate and evaluate MCZ as an intranasal in situ gel with increased residence time and permeability. Methods: We made an inclusion complex of MCZ using various cyclodextrins as a complexing agent to help the drug dissolve better. The complexes were studied, and the ones that were better at dissolving were chosen to be used in the creation of an in situ gel with poloxamer 407 (17–20% w/v) and hyaluronic acid (0.25–0.75% w/v). Prepared formulas were subjected to various evaluation tests, and the optimum formula was subjected to an ex vivo permeation study. Results: Hydroxypropyl-cyclodextrin (HP-CD) complexation increased the solubility of MCZ. A prepared complex (10 mg of MCZ) was used for nasal in situ gel preparation. Formula (F3) containing 17% poloxamer 407 and 0.75% hyaluronic acid exhibited favorable characteristics, including optimal gelation temperature (33.33°C), drug content (100.51%), gel strength (35.0 seconds), spreadability (4.2 cm), and 98.52% in vitro drug release over 5 hours in simulated nasal fluid (pH 6.8), and provided considerably high permeability. Conclusions: A mucoadhesive in situ gel formulation of MCZ (HP-β-CD) is a promising nasal formulation for the management of nausea and vomiting.
... Consequently, there's no need to take the dose form out after the drug has run out. [22] ...
... Review Article 2. Systemic: Intranasal (IN) delivery, a prospective medication administration method for systemic absorption of analgesics, sedatives, hormones, vaccines, and cardiovascular medicines via the nasal mucosa, has received a lot more attention in recent years. in light of the nose passage's structure and physiology, which include its highly vascularized epithelium, ready access, extensive surface area, permeable endothelium membrane, high total blood flow, and suppression of firstpass metabolism, this is the case. [7]. ...
Nasal medication administration has been used for therapeutic and recreational purposes since the dawn of civilization. The importance of and interest in the systemic effects of medications taken orally has grown over the past few decades. Medications administered intra-nasally provide an intriguing option to the parenteral route, which can occasionally be uncomfortable. These might involve avoiding pre-systemic release in the digestive tract and eliminating the first-pass effect (GIT), necessitating the use of a tiny dose of a specific medicine. Lowering the dose will lessen the negative effects and, ultimately, lower the cost of the medication. The likelihood for intranasal medication delivery to overcome certain significant drawbacks is linked with the other stated routes making it the most exciting path for drug administration. This review covered how in situ gel became more popular than previous nasal administration forms.
The intranasal (IN) route of administration is important for topical drugs and drugs intended to act systemically. More recently, direct nose-to-brain input was considered to bypass the blood-brain barrier.Processes related to IN absorption and nose-to-brain distribution are complex and depend, sometimes in contrasting ways, on chemico-physical and structural parameters of the compounds, and on formulation options.Due to the intricacies of these processes and despite the large number of articles published on many different IN compounds, it appears that absorption after IN dosing is not yet fully understood. In particular, at variance of the understanding and modelling approaches that are available for predicting the pharmacokinetics (PK) following oral administration of xenobiotics, it appears that there is not a similar understanding of the chemico-physical and structural determinants influencing drug absorption and disposition of compounds after IN administration, which represents a missed opportunity for this research field. This is even more true regarding the understanding of the direct nose-to-brain input. Due to this, IN administrations may represent an interesting and open research field for scientists aiming to develop PK property predictions tools, mechanistic PK models describing rate and extent of IN absorption, and translational tools to anticipate the clinical PK following IN dosing based on in vitro and in vivo non clinical experiments.This review intends to provide: i) some basic knowledge related to the physiology of PK after IN dosing, ii) a non-exhaustive list of preclinical and clinical examples related to compounds explored for the potential nose-to-blood and nose-to-brain passage, and iii) the identification of some areas requiring improvements, the understanding of which may facilitate the development of IN drug candidates.
Nasal drug delivery has received a great deal of attention as a convenient, reliable, and promising method for the systemic administration of drugs. It is especially for those molecules which are ineffective orally and only effective if administered by injection. The nasal route of drug delivery has advantages over the other alternative systems of non-invasive drug administration. The present review is an attempt to provide some information concerning nasal drug delivery system such as limitations, advantages, mechanism of drug absorption, anatomy of nasal cavity, factors affecting of nasal drug delivery, strategies to enhance nasal absorption, strategies to extend duration of drug formulations within the nasal cavity, leading to improved nasal drug absorption, novel drug formulations, sorts of nasal drug delivery system with uses of nasal drug delivery in various diseases, and recent advancement of nasal delivery systems.
A bacterial phosphotriesterase was employed as an experimental paradigm to examine the effects of multiple factors, such as the molecular constructs, the ligands used during protein expression and purification, the crystallization conditions and the space group, on the visualization of molecular complexes of ligands with a target enzyme. In this case, the ligands used were organophosphates that are fragments of the nerve agents and insecticides on which the enzyme acts as a bioscavenger. 12 crystal structures of various phosphotriesterase constructs obtained by directed evolution were analyzed, with resolutions of up to 1.38 Å. Both apo forms and holo forms, complexed with the organophosphate ligands, were studied. Crystals obtained from three different crystallization conditions, crystallized in four space groups, with and without N-terminal tags, were utilized to investigate the impact of these factors on visualizing the organophosphate complexes of the enzyme. The study revealed that the tags used for protein expression can lodge in the active site and hinder ligand binding. Furthermore, the space group in which the protein crystallizes can significantly impact the visualization of bound ligands. It was also observed that the crystallization precipitants can compete with, and even preclude, ligand binding, leading to false positives or to the incorrect identification of lead drug candidates. One of the co-crystallization conditions enabled the definition of the spaces that accommodate the substituents attached to the P atom of several products of organophosphate substrates after detachment of the leaving group. The crystal structures of the complexes of phosphotriesterase with the organophosphate products reveal similar short interaction distances of the two partially charged O atoms of the P—O bonds with the exposed β-Zn²⁺ ion and the buried α-Zn²⁺ ion. This suggests that both Zn²⁺ ions have a role in stabilizing the transition state for substrate hydrolysis. Overall, this study provides valuable insights into the challenges and considerations involved in studying the crystal structures of ligand–protein complexes, highlighting the importance of careful experimental design and rigorous data analysis in ensuring the accuracy and reliability of the resulting phosphotriesterase–organophosphate structures.
Neurological diseases are one of the most pressing issues in modern times worldwide. It thus possesses explicit attention from researchers and medical health providers to guard public health against such an expanding threat. Various treatment modalities have been developed in a remarkably short time but, unfortunately, have yet to lead to the wished-for efficacy or the sought-after clinical improvement. The main hurdle in delivering therapeutics to the brain has always been the blood-brain barrier which still represents an elusive area with lots of mysteries yet to be solved. Meanwhile, nanotechnology has emerged as an optimistic platform that is potentially holding the answer to many of our questions on how to deliver drugs and treat CNS disorders using novel technologies rather than the unsatisfying conventional old methods. Nanocarriers can be engineered in a way that is capable of delivering a certain therapeutic cargo to a specific target tissue. Adding to this mind-blowing nanotechnology, the revolutionizing gene-altering biologics can have the best of both worlds, and pave the way for the long-awaited cure to many diseases, among those diseases thus far are Alzheimer’s disease (AD), brain tumors (glioma and glioblastoma), Down syndrome, stroke, and even cases with HIV. The review herein collects the studies that tested the mixture of both sciences, nanotechnology, and epigenetics, in the context of brain therapeutics using three main categories of gene-altering molecules (siRNA, miRNA, and CRISPR) with a special focus on the advancements regarding the new favorite, intranasal route of administration.
One of the principal impediments for the treatment of neurological conditions is the lack of ability of most of the medicinal agents to evade the blood–brain barrier. Among all the novel approaches to bypass the blood–brain barrier, nose to brain transport is the most patient compliant, non-invasive and effective approach. It directly transports drugs to the CNS via the trigeminal and olfactory nerves present in the nasal cavity. This review article focuses on anatomy and physiology of nasal cavity, potential of intranasal drug delivery, mechanisms of drug transport to brain, its advantages and limitations, novel intranasal formulations, marketed products, factors affecting nose to brain transport, formulation consideration of intranasal products and the future perspectives of CNS targeting via intranasal drug administration.
