1. PLGA Nanoparticles Based Mucoadhesive Nasal In Situ Gel for Enhanced Brain Delivery of Topiramate.
- Author
-
Tanna V, Vora A, Shah P, Nair AB, Shah J, and Sawarkar SP
- Subjects
- Animals, Rats, Male, Particle Size, Fructose administration & dosage, Fructose pharmacokinetics, Fructose chemistry, Drug Carriers chemistry, Drug Liberation, Drug Delivery Systems methods, Lactic Acid chemistry, Lactic Acid administration & dosage, Polyglycolic Acid chemistry, Administration, Oral, Topiramate administration & dosage, Topiramate pharmacokinetics, Nanoparticles chemistry, Administration, Intranasal methods, Polylactic Acid-Polyglycolic Acid Copolymer chemistry, Gels, Rats, Sprague-Dawley, Brain metabolism, Brain drug effects, Nasal Mucosa metabolism, Nasal Mucosa drug effects
- Abstract
Oral Topiramate therapy is associated with systemic adverse effects including paresthesia,abdominal pain, and fluctuations in plasma levels. The purpose of this research was to develop an intranasal in situ gel based system comprising Topiramate polymeric nanoparticles and evaluate its potential both in vitro and in vivo. Poly (lactic-co-glycolic acid) (PLGA)nanoparticles prepared by nanoprecipitation method were added into the in situ gelling system of Poloxamer 407 and HPMC K4M. Selected formulation (TG5) was evaluated for physicochemical properties, nasal permeation and in vivo pharmacokinetics in rats. PLGAnanoparticles (O1) exhibited low particle size (~ 144.4 nm), good polydispersity index (0.202), negative zeta potential (-12.7 mV), and adequate entrapment efficiency (64.7%). Developed in situ gel showed ideal pH (6.5), good gelling time (35 s), gelling temperature(37℃), suitable viscosity (1335 cP)and drug content of 96.2%. In vitro drug release conformedto Higuchi release kinetics, exhibiting a biphasic pattern of initial burst release and sustained release for 24 h. Oral administration of the drug to Sprague-Dawley rats (G3) showed higher plasma C
max (504 ng/ml, p < 0.0001) when compared to nasal delivery of in situ gel (G4) or solution (G5). Additionally, AUC0-α of G3 (8786.82 ng/ml*h) was considerably higher than othergroups. Brain uptake data indicates a higher drug level with G4 (112.47 ng /ml) at 12 h when compared to G3. Histopathological examination of groups; G1 (intranasal saline), G2(intranasal placebo), G3, G4, and G5 did not show any lesions of pathological significance. Overall, the experimental results observed were promising and substantiated the potential of developed in situ gel for intranasal delivery., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)- Published
- 2024
- Full Text
- View/download PDF