Quantification and Evaluations of Catechin Hydrate Polymeric Nanoparticles Used in Brain Targeting for the Treatment of Epilepsy

Abstract

To formulate novel chitosan (CS)-coated–PLGA–nanoparticles (NPs) using a central composite design approach and use them in order to improve brain bioavailability for catechin hydrate (CH) through direct nose-to-central nervous system (CNS) delivery for the evaluation of a comparative biodistribution study of CH by the newly developed ultra high performance liquid chromatography mass spectroscopy and mass spectroscopy (UHPLC-MS/MS) method in the treatment of epilepsy. For PLGA–NPs’ preparation, a double emulsion-solvent evaporation method was used, where a four-factor, three-level central composite design was used to obtain the best nanoformulation. For the optimization, four independent variables were chosen, that is, PLGA, polyvinyl alcohol (PVA), sonication time, and temperature. The optimized PLGA–NPs were further coated with chitosan and assessed for drug release, nasal permeation study, as well as a comparative pharmacokinetic and pharmacodynamic study. Independent and dependent variables helped to optimize the best nanoformulation based on the composition of PLGA (50.0 mg), PVA (1.10%), sonication time (90.0 s), and temperature (25.0 °C). The values of dependent variables were observed, such as polydispersity index (PDI), particle size, and zeta potential (ZP)—that is, 0.106 ± 0.01, 93.46 ± 3.94 nm, and −12.63 ± 0.08 mV, respectively. The ZPs of CS-coated PLGA–NPs were changed from negative to positive value with some alteration in the distribution of particle size. Excellent mucoadhesive-nature of CS–CH–PLGA–NPs as compared with CH–S and CH–PLGA–NPs was seen, with a retention time of 0.856 min and m/z of 289.23/245.20 for CH, together with a retention time of 1.04 min and m/z of 301.21/151.21 for Quercetin as an internal standard (IS). For a linear range (1–1000 ng mL−1), % accuracy (93.07–99.41%) and inter- and intraday % precision (0.39–4.90%) were determined. The improved Cmax with area under curve (AUC)0–24 was found to be highly significant (p < 0.001) in Wistar rats’ brain as compared with the i.n. and i.v. treated group based on the pharmacokinetics (PK) results. Furthermore, CS–CH–PLGA–NPs were found to be more significant (p < 0.001) for the treatment of seizure threshold rodent models, that is, increasing current electroshock and pentylenetetrazole-induced seizures. A significant role of CS–CH–PLGA–NPs was observed, that is, p < 0.001, for the enhancement of brain bioavailability and the treatment of epilepsy.

A Reevaluation of Chitosan-Decorated Nanoparticles to Cross the Blood-Brain Barrier

“…The results demonstrated a higher amount of drug permeated to the brain when the nanoparticles were coated with the polymer. Furthermore, mucoadhesion at nasal mucosa suggested a high permanence of the nanosystem, with a release profile longer than 48 h [20][21][22]. Similar findings were observed with polymeric nanoparticles administered via intranasal to treat conditions such as cerebral ischemia (PLC nanoparticles) [23,24], for nociceptive pain (PLA (poly-lactide acid) nanoparticles) [90], or to transport neuroprotective molecules such as coenzyme Q10, or contrast agents (PLGA nanoparticles).…”

“…Chitosan is a polymer natural widely utilized in different applications and approved for human use; it is a biodegradable, biocompatible, non-toxic, non-allergenic, and low-priced biomaterial; thus, chitosan is a suitable material for medical purposes [15]. Numerous studies have evaluated chitosan-coated nanosystems for the transportation of therapeutic compounds for the potential treatment of Alzheimer´s disease, Parkinson's disease, gliomas, cerebral ischemia, and schizophrenia [16][17][18][19][20][21][22][23][24].…”

A Chitosan-PLGA based catechin hydrate nanoparticles used in targeting of lungs and cancer treatment

“…The in vitro release of CTH from the CTH-PLGA-NPs & CS-PLGA-NPs were carried out in two separate release-medium with pH 7.40 and pH 5.50 in order to initiate the physiologic and acidic condition of cancer cells with slight modification ( Ahmad et al, 2018a , Ahmad et al, 2019 , Ahmad et al, 2020b ). Equal quantities of CTH-PLGA NP samples were packed in a dialysis sac and suspended in a 25.0 ml of the respective release medium having different pH 5.50 and pH 7.40.…”

“…1.0 ml every test sample was withdrawn from each sampling-time point. After the withdrawal of every test sample, it was filtered through 0.20 μm syringe-filter and then analysed by UHPLC–MS/MS-method ( Ahmad et al, 2018a , Ahmad et al, 2019 , Ahmad et al, 2020b ).…”

Natural Polysaccharide Carriers in Brain Delivery: Challenge and Perspective

“…CH-coated PLGA and PCL nanoparticles for intranasal Rasagiline (RGN) [104], cathechin hydrate (CAT) [105] and glycyrrhizic acid (GA) [106] release were proposed for the treatment of various brain disorders. In all studies, pharmacokinetic experiments conducted in Wistar rats showed a significant high bioavailability and C max over the intravenous treatment group, confirming the suitability of nanoparticulate system as targeted brain dosage forms of hydrophilic molecules with undesirable side effects and high-hepatic first-pass metabolism.…”