Development of novel bioadhesive granisetron hydrochloride spanlastic gel and insert for brain targeting and study their effects on rats (original) (raw)
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In Situ-Based Gels for Nose to Brain Delivery for the Treatment of Neurological Diseases
Pharmaceutics, 2018
In situ-based gel drug delivery systems that can bypass the blood-brain barrier, deliver the therapeutics to the desired site, reduce peripheral toxicity and control drug release kinetics have been developed. Some of the therapeutics used to treat neurological diseases suffer from poor bioavailability. Preclinical reports from several researchers have proven that the delivery of drugs to the brain via the nose-to-brain route using in situ gels holds great promise. However, safety issues on the toxicity of the nasal mucosa, transportation of the drugs to specific brain regions and determination of the required dose are factors that must be considered when designing these gels. This review will be focused on in situ-based gels that are used for the delivery of therapeutics via the nose-to-brain route, preclinical reports and challenges.
Evaluation of intranasal delivery route of drug administration for brain targeting
Brain Research Bulletin, 2018
The acute or chronic drug treatments for different neurodegenerative and psychiatric disorders are challenging from several aspects. The low bioavailability and limited brain exposure of oral drugs, the rapid metabolism, elimination, the unwanted side effects and also the high dose to be added mean both inconvenience for the patients and high costs for the patients, their family and the society. The reason of low brain penetration of the compounds is that they have to overcome the blood-brain barrier which protects the brain against xenobiotics. Intranasal drug administration is one of the promising options to bypass blood-brain barrier, to reduce the systemic adverse effects of the drugs and to lower the doses to be administered. Furthermore, the drugs administered using nasal route have usually higher bioavailability, less side effects and result in higher brain exposure at similar dosage than the oral drugs. In this review the focus is on giving an overview on the anatomical and cellular structure of nasal cavity and absorption surface. It presents some possibilities to enhance the drug penetration through the nasal barrier and summarizes some in vitro, ex vivo and in vivo technologies to test the drug delivery across the nasal epithelium into the brain. Finally, the authors give a critical evaluation of the nasal route of administration showing its main advantages and limitations of this delivery route for CNS drug targeting.
Innovative approach for nasal drug delivery system for brain target
Zenodo (CERN European Organization for Nuclear Research), 2021
The goal of brain drug targeting technology is the delivery of therapeutics across the blood brain barrier (BBB), including the human BBB. Nose to brain drug delivery has received a great deal of attention as a non-invasive, convenient and reliable drug delivery system. For the systemic and targetedadministration of drug. The various drug deliveries through some drug transport pathways, Factor influencing nasal drug absorption, formulation strategies nose to brain, colloidal carriers in nose to brain drug delivery system and nasal delivery systems. Physiological barriers (BBB) that restricts the delivery of drug to CNS. Thus intranasal route has attracted a wide attention of convenient, noninvasive, reliable, and safe route to achieve faster and higher level of drug in the brain through olfactory region by passing blood brain barrier. Intranasal administration rapid onset of action, no first-pass effect , no gastrointestinal degradation lungs toxicity and non-invasiveness application and also improves bioavailability.
Formulation and Development of Mucoadhesive Nasal Drug Delivery of Ropinirol HCL for Brain Targeting
International Journal of Applied Pharmaceutics
Objective: The purpose of this research was to create polymeric nanoparticles of ropinirole HCl for nasal administration utilising the ionic gelation process. Methods: The preparation method was optimized using box-behnken design employing chitosan concentration, guar gum concentration and surfactant concentration as independent variables were as Encapsulation efficiency and mucoadhesion of the formulation were selected as dependent variables. Differential scanning calorimetry and infrared spectroscopy analysis of the drug and polymers revealed that the drug and excipients are physicochemically compatible. Studies on entrapment efficiency, drug content, and In vitro release were conducted on the nanoparticles. Results: Each formulation was determined to have a drug content of between 60% and 70% and an entrapment efficiency of between 65% and 84%. In vitro drug release tests demonstrated that ropinirole HCl will release between 65 and 81 percent after 5 h. Conclusion: The results sh...
International Journal of Applied Pharmaceutics, 2023
Objective: The purpose of this research was to create polymeric nanoparticles of ropinirole HCl for nasal administration utilising the ionic gelation process. Methods: The preparation method was optimized using box-behnken design employing chitosan concentration, guar gum concentration and surfactant concentration as independent variables were as Encapsulation efficiency and mucoadhesion of the formulation were selected as dependent variables. Differential scanning calorimetry and infrared spectroscopy analysis of the drug and polymers revealed that the drug and excipients are physicochemically compatible. Studies on entrapment efficiency, drug content, and In vitro release were conducted on the nanoparticles. Results: Each formulation was determined to have a drug content of between 60% and 70% and an entrapment efficiency of between 65% and 84%. In vitro drug release tests demonstrated that ropinirole HCl will release between 65 and 81 percent after 5 h. Conclusion: The results showed that the particle size, encapsulation effectiveness, and drug content were all significantly affected by the amounts of chitosan and guar gum.
European Journal of Pharmaceutics and Biopharmaceutics, 2009
Absorption enhancer Blood-brain barrier Brain targeting FITC-dextran Hyaluronic acid In vitro drug release Mucoadhesive Nasal drug delivery Rheology a b s t r a c t Intranasal administration of molecules has been investigated as a non-invasive way for delivery of drugs to the brain in the last decade. Circumvention of both the blood-brain barrier and the first-pass elimination by the liver and gastrointestinal tract is considered as the main advantages of this method. Because of the rapid mucociliary clearance in the nasal cavity, bioadhesive formulations are needed for effective targeting. Our goal was to develop a formulation containing sodium hyaluronate, a well-known mucoadhesive molecule, in combination with a non-ionic surfactant to enhance the delivery of hydrophilic compounds to the brain via the olfactory route. Fluorescein isothiocyanate-labeled 4 kDa dextran (FD-4), used as a test molecule, was administered nasally in different formulations to Wistar rats, and detected in brain areas by fluorescent spectrophotometry. Hyaluronan increased the viscosity of the vehicles and slowed down the in vitro release of FD-4. Significantly higher FD-4 transport could be measured in the majority of brain areas examined, including olfactory bulb, frontal and parietal cortex, hippocampus, cerebellum, midbrain and pons, when the vehicle contained hyaluronan in combination with absorption enhancer. The highest concentrations of FD-4 could be detected in the olfactory bulbs, frontal and parietal cortex 4 h after nasal administration in the mucoadhesive formulation. Intravenous administration of a hundred times higher dose of FD-4 resulted in a lower brain penetration as compared to nasal formulations. Morphological examination of the olfactory system revealed no toxicity of the vehicles. Hyaluronan, a non-toxic biomolecule used as a mucoadhesive in a nasal formulation, increased the brain penetration of a hydrophilic compound, the size of a peptide, via the nasal route.
A Overview of Nasal to Brain Drug Delivery
2020
Use of the nasal route for the delivery of challenging drugs such as small polar molecules, vaccines, hormones, peptides and proteins has created much interest in nowadays. Due to the high permeability, high vasculature, low benzymatic environment of nasal cavity and avoidance of hepatic first pass metabolism are well suitable for systemic delivery of drug molecule via nose. The unique relationship between nasal cavity and cranial cavity tissues in anatomy and physiology makes intranasal delivery to the brain feasible. An intranasal delivery provides some drugs with short channels to bypass the blood–brain barrier (BBB), especially for those with fairly low brain concentrations after a routine delivery, thus greatly enhancing the therapeutic effect on brain diseases. In the past two decades, a good number of encouraging outcomes have been reported in the treatment of diseases of the brain or central nervous system (CNS) through nasal the paper also includes. The different types of b...
Drug Delivery and Translational Research, 2020
Methyl cellulose (MC) based nasal in situ gels were developed to enhance the brain delivery of piribedil (PBD), an anti-Parkinson's drug. Different grades of MC and several solutes (NaCl, KCl, Na.Citrate, STPP, PEG-6000, sucrose, etc.) were screened to formulate thermo-responsive nasal in situ gelling systems. Formulations were evaluated for their sol-gel transition temperature and time, rheological behaviour, in vitro drug release, mucociliary clearance (MCC), ex vivo nasal toxicity, and in vivo brain availability studies in Wistar rats. Intranasal (i.n.) administration was carried out using a cannula-microtip setup to deliver PBD at the olfactory region of the nose. The concentration and viscosity grade of MC and also the concentration and type of solute used were found to affect the rheological behaviour of the formulations. Among the solutes tested, NaCl was found to be effective for formulating MC in situ gels. The developed in situ gels significantly delayed the MCC of PBD from the site of administration when compared with conventional suspension (p < 0.05). Further, formulations with higher gel strength showed lower in vitro drug release rate and longer intranasal residence (delayed MCC) (p < 0.05). The absolute brain availability (brain AUC 0-t) of PBD increased to 35.92% with i.n. delivery when compared to 4.71% with oral administration. Overall, it can be concluded that intranasal delivery of PBD is advantageous when compared to the currently practiced oral therapy.
Journal of Controlled Release, 2007
There is an increasing need for nasal drug delivery systems that could improve the efficiency of the direct nose to brain pathway especially for drugs for treatment of central nervous system disorders. Novel approaches that are able to combine active targeting of a formulation to the olfactory region with controlled release bioadhesive characteristics, for maintaining the drug on the absorption site are suggested. If necessary an absorption enhancer could be incorporated.
Drug Delivery Systems from Nose to Brain
Curr Pharm Biotechnol, 2012
The treatment of brain disorders is particularly challenging due to the presence of a variety of formidable obstacles to deliver drugs selectively and effectively to the brain. Blood-brain-barrier (BBB) constitutes the major obstacle to the uptake of drugs into the brain following systemic administration. Intranasal delivery offers a non-invasive and convenient method to bypass the BBB and delivery of therapeutics directly to the brain. The review discusses the potential of intranasal route to deliver drugs to the brain, the mechanisms and pathways of direct nose to brain drug transport, the various factors influencing transnasal drug absorption, the conventional and novel intranasal drug delivery systems, the various intranasal drug delivery techniques and devices, and examples of brain drug transport that have been feasible in treating various brain disorders. Moreover, products on the market, investigational drugs, and the author's perceptions about the prospect of intranasal delivery for treating brain disorders are also been discussed.