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Srinivasan, Venkatesh, Sudheer, Preethi, Bhavani, Keserla, Muthu Kumar, Arumugam. (1404). A nanoparticle loaded nasal sol-gel system of midazolam hydrochloride for the management of intermittent seizures. , 12(3), 421-432. doi: 10.22038/nmj.2025.80993.2006
Venkatesh Prasad Srinivasan; Preethi Sudheer; Keserla Bhavani; Arumugam Muthu Kumar. "A nanoparticle loaded nasal sol-gel system of midazolam hydrochloride for the management of intermittent seizures". , 12, 3, 1404, 421-432. doi: 10.22038/nmj.2025.80993.2006
Srinivasan, Venkatesh, Sudheer, Preethi, Bhavani, Keserla, Muthu Kumar, Arumugam. (1404). 'A nanoparticle loaded nasal sol-gel system of midazolam hydrochloride for the management of intermittent seizures', , 12(3), pp. 421-432. doi: 10.22038/nmj.2025.80993.2006
Srinivasan, Venkatesh, Sudheer, Preethi, Bhavani, Keserla, Muthu Kumar, Arumugam. A nanoparticle loaded nasal sol-gel system of midazolam hydrochloride for the management of intermittent seizures. , 1404; 12(3): 421-432. doi: 10.22038/nmj.2025.80993.2006

A nanoparticle loaded nasal sol-gel system of midazolam hydrochloride for the management of intermittent seizures

Nanomedicine Journal
مقاله 6، دوره 12، شماره 3، مهر 2025، صفحه 421-432    اصل مقاله (1.29 M)
نوع مقاله: Research Paper
شناسه دیجیتال (DOI): 10.22038/nmj.2025.80993.2006
نویسندگان
Venkatesh Prasad Srinivasan1؛ Preethi Sudheer* 2؛ Keserla Bhavani3؛ Arumugam Muthu Kumar4
1Department of Pharmaceutics, Krupanidhi College of Pharmacy, Bangalore, Karnataka, India
2Department of Pharmaceutics, Krupanidhi College of Pharmacy, Bangalore, Karnataka, India
3Department of Pharmacology, Oxford College of Pharmacy, Bangalore , Karnataka, India
4Department of Pharmacology, Oxford College of Pharmacy, Bangalore, Karnataka, India
چکیده
Objective(s): Midazolam hydrochloride is a short-acting hypnotic sedative with anticonvulsant properties. Considering the poor bioavailability, rapid elimination, and inconvenience of administering oral medication in epileptic conditions, this study proposed the use of a nanoparticulate in situ nasal gel system for midazolam to achieve an optimum therapeutic effect.
Materials and Methods: Drug-loaded PLGA nanoparticles were prepared by an emulsion-solvent evaporation method utilizing a Box–Behnken design concentrated on particle size, zeta potential, and drug entrapment efficiency as responses. The optimized nanoparticles were incorporated into a 0.2% w/v gellan gum solution. The nanoparticle-loaded gel was studied for ex vivo drug permeation through excised sheep nasal mucosa. The anticonvulsive activity of the gel was compared with that of the marketed midazolam nasal spray (0.5 mg/0.1 ml).
Results: Particle size (200 nm to 310 nm), zeta potential (-25mV to -31mV), and entrapment efficiency (81.23±0.21 to 93.32±0.28%) were observed in the formulations. The drug release from the formulations over 24 h was found to be 75.32±0.028to 84.63±0.061%. Particle size and zeta potential were best fitted to the quadratic model, and an entrapment efficiency linear model was suggested. The ex vivo permeation studies of the optimized nanoparticle-incorporated gel formulation exhibited a fourfold increase in flux and permeability coefficient in comparison to the pure drug-incorporated gel. The anticonvulsive effect in pentylenetetrazol (PTZ)-induced rat model epilepsy showed a similar anticonvulsive profile to that of the marketed nasal spray.
Conclusion: Drug-loaded nanoparticles incorporated in situ gel would be a promising, biocompatible, and non-invasive approach to achieve the required therapeutic efficacy by sustained and direct action on brain cells
کلیدواژه‌ها
Nasal ,Gellan gum؛ Midazolam؛ Nanoparticles؛ PLGA
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