Formulation and Evaluation of Niosomal in situ Nasal Gel of a Serotonin Receptor Agonist, Buspirone Hydrochloride for the Brain Delivery via Intranasal Route

2018 ◽  
Vol 6 (1) ◽  
pp. 69-78 ◽  
Author(s):  
Dyandevi Mathure ◽  
Jyotsana R Madan ◽  
Kishore N. Gujar ◽  
Ashok Tupsamundre ◽  
Hemant A. Ranpise ◽  
...  
Author(s):  
SARASWATHI T. S. ◽  
MOTHILAL M.

Objective: Aim of the study is to develop rivastigmine-loaded niosomal in situ gel via the intranasal route to the brain by crossing the Blood-Brain Barrier. For the treatment of Alzheimer’s disease, it provides a speedy onset of action, a faster therapeutic effect, avoidance of the first-pass metabolism, and enhanced bioavailability. Methods: Rivastigmine niosomal in situ nasal gel was developed, refined and tested with the goal of delivering the medicine to the brain via the intranasal route Rivastigmine niosomes were formulated by thin-film hydration technique, optimized using (32) factorial design and characterized for its physicochemical parameters. Rivastigmine-loaded niosomes were further incorporated into Carbopal-934P and HPMC-K4M liquid gelling system to form in situ nasal gel. The resulting solution was evaluated for several parameters including, viscosity at pH 5 and pH 6, gelling capacity and gelling time. Results: Optimized best formulation containing span 60 (A) and cholesterol (B) with (1:0.5) ratio identified from the model developed from Design-Expert®12 software, exhibited Entrapment efficiency (76.5±0.23%), particle size (933.4±0.14 nm), in vitro drug release maximum (68.94±0.26%) at 8th hour and further studied for its characteristics by SEM and TEM showed stable vesicles. Polynomial equations of Y1, Y2, and Y3 were conducted and ANOVA results showed a significant impact (p<0.05) on three levels. In vivo perfusion studies using rat model showed, the niosomes developed has good perfusion compared to pure drug with 27.2% of drug absorption in the brain at the end of 3 h. In vitro permeation of Rivastigmine through the dialysis membrane showed that 60.74% w/w drug permeated after 8 h. The formation of stable vesicles was proved by Zeta potential measurements and SEM analysis. Conclusion: Optimized formulation had greater perfusion and was expected to have a good bioavailability compared to conventional other drug delivery systems.


2020 ◽  
Vol 21 (14) ◽  
pp. 1136-1143 ◽  
Author(s):  
Javed Ahmad ◽  
Md. Rizwanullah ◽  
Saima Amin ◽  
Musarrat Husain Warsi ◽  
Mohammad Zaki Ahmad ◽  
...  

Background: Nanostructured lipid carriers (NLCs) are in high demand in the existing pharmaceutical domain due to its high versatility. It is the newer generation of lipid nanoparticulate systems having a solid matrix and greater stability at room temperature. Objective: To review the evidence related to the current state of the art of the NLCs system and its drug delivery perspectives to the brain. Methods: Scientific data search, review of the current state of the art and drug delivery perspectives to the brain for NLCs were undertaken to assess the applicability of NLCs in the management of neurological disorders through an intranasal route of drug administration Results: NLCs are designed to fulfill all the industrial needs like simple technology, low cost, scalability, and quantifications. Biodegradable and biocompatible lipids and surfactants used for NLCs have rendered them acceptable from regulatory perspectives as well. Apart from these, NLCs have unique properties of high drug payload, modulation of drug release profile, minimum drug expulsion during storage, and incorporation in various dosage forms like gel, creams, granules, pellets, powders for reconstitution and colloidal dispersion. Ease of surface- modification of NLCs enhances targeting efficiency and reduces systemic toxicity by providing site-specific delivery to the brain through the intranasal route of drug administration. Conclusion: The present review encompasses the in-depth discussion over the current state of the art of NLCs, nose-to-brain drug delivery perspectives, and its theranostic application as useful tools for better management of various neurological disorders. Further, pharmacokinetic consideration and toxicity concern is also discussed specifically for the NLCs system exploited in nose-to-brain delivery.


2020 ◽  
Vol 26 (19) ◽  
pp. 2291-2305 ◽  
Author(s):  
Saurabh Mittal ◽  
Muhammad U. Ashhar ◽  
Farheen F. Qizilbash ◽  
Zufika Qamar ◽  
Jasjeet K. Narang ◽  
...  

Background: Human brain is amongst the most complex organs in human body, and delivery of therapeutic agents across the brain is a tedious task. Existence of blood brain barrier (BBB) protects the brain from invasion of undesirable substances; therefore it hinders the transport of various drugs used for the treatment of different neurological diseases including glioma, Parkinson's disease, Alzheimer's disease, etc. To surmount this barrier, various approaches have been used such as the use of carrier mediated drug delivery; use of intranasal route, to avoid first pass metabolism; and use of ligands (lactoferrin, apolipoprotein) to transport the drug across the BBB. Ligands bind with proteins present on the cell and facilitate the transport of drug across the cell membrane via. receptor mediated, transporter mediated or adsorptive mediated transcytosis. Objective: The main focus of this review article is to illustrate various studies performed using ligands for delivering drug across BBB; it also describes the procedure used by various researchers for conjugating the ligands to the formulation to achieve targeted action. Methods: Research articles that focused on the used of ligand conjugation for brain delivery and compared the outcome with unconjugated formulation were collected from various search engines like PubMed, Science Direct and Google Scholar, using keywords like ligands, neurological disorders, conjugation, etc. Results and Conclusion: Ligands have shown great potential in delivering drug across BBB for treatment of various diseases, yet extensive research is required so that the ligands can be used clinically for treating neurological diseases.


2020 ◽  
Vol Volume 15 ◽  
pp. 5253-5264
Author(s):  
Usama A Fahmy ◽  
Osama AA Ahmed ◽  
Shaimaa M Badr-Eldin ◽  
Hibah M Aldawsari ◽  
Solomon Z Okbazghi ◽  
...  

1992 ◽  
Vol 57 (1) ◽  
pp. 194-203 ◽  
Author(s):  
Karel Šindelář ◽  
Vojtěch Kmoníček ◽  
Marta Hrubantová ◽  
Zdeněk Polívka

(Arylthio)benzoic acids IIa - IIe and VIb - VId were transformed via the acid chlorides to the N,N-dimethylamides which were reduced either with diborane "in situ" or with lithium aluminium hydride to N,N-dimethyl-(arylthio)benzylamines Ia - Ie and Vb - Vd. Leuckart reaction of the aldehydes IX and X with dimethylformamide and formic acid afforded directly the amines Va and Ve. Demethylation of the methoxy compounds Ia and Ve with hydrobromic acid resulted in the phenolic amines If and Vf. The most interesting N,N-dimethyl-4-(phenylthio)benzylamine (Va) hydrochloride showed affinity to cholinergic and 5-HT2 serotonin receptors in the rat brain and some properties considered indicative of antidepressant activity (inhibition of serotonin re-uptake in the brain and potentiation of yohimbine toxicity in mice).


PLoS ONE ◽  
2017 ◽  
Vol 12 (12) ◽  
pp. e0189478 ◽  
Author(s):  
Yingting Wang ◽  
Shulong Jiang ◽  
Hongli Wang ◽  
Haiyan Bie

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