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Tailoring Risperidone-Loaded Glycethosomal In Situ Gels Using Box–Behnken Design for Treatment of Schizophrenia-Induced Rats via Intranasal Route
Schizophrenic patients often face challenges with adherence to oral regimens. The study aimed to highlight the potentiality of intranasal ethanol/glycerin-containing lipid-nanovesicles (glycethosomes) incorporated into in situ gels for sustaining anti-psychotic risperidone (RS) release. The Box–Behn...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10675145/ https://www.ncbi.nlm.nih.gov/pubmed/38004501 http://dx.doi.org/10.3390/pharmaceutics15112521 |
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author | Abdallah, Marwa H. El-Horany, Hemat El-Sayed El-Nahas, Hanan M. Ibrahim, Tarek M. |
author_facet | Abdallah, Marwa H. El-Horany, Hemat El-Sayed El-Nahas, Hanan M. Ibrahim, Tarek M. |
author_sort | Abdallah, Marwa H. |
collection | PubMed |
description | Schizophrenic patients often face challenges with adherence to oral regimens. The study aimed to highlight the potentiality of intranasal ethanol/glycerin-containing lipid-nanovesicles (glycethosomes) incorporated into in situ gels for sustaining anti-psychotic risperidone (RS) release. The Box–Behnken Design (BBD) was followed for in vitro characterization. Glycethosomal-based in situ gels were examined by physical, ex vivo, and in vivo investigations. The ethanol impact on minimizing the vesicle size (VS) and enhancing the zeta potential (ZP) and entrapment efficiency (EE%) of nanovesicles was observed. Glycerin displayed positive action on increasing VS and ZP of nanovesicles, but reduced their EE%. After incorporation into various mucoadhesive agent-enriched poloxamer 407 (P407) in situ gels, the optimized gel containing 20% P407 and 1% hydroxypropyl methyl cellulose-K4M (HPMC-K4M) at a 4:1 gel/glycethosomes ratio showed low viscosity and high spreadability with acceptable pH, gel strength, and mucoadhesive strength ranges. The ethanol/glycerin mixture demonstrated a desirable ex vivo skin permeability of RS through the nasal mucosa. By pharmacokinetic analysis, the optimized gel showed eight-fold and three-fold greater increases in RS bioavailability than the control gel and marketed tablet, respectively. Following biochemical assessments of schizophrenia-induced rats, the optimized gel boosted the neuroprotective, anti-oxidant, and anti-inflammatory action of RS in comparison to other tested preparations. Collectively, the intranasal RS-loaded glycethosomal gel offered a potential substitute to oral therapy for schizophrenic patients. |
format | Online Article Text |
id | pubmed-10675145 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106751452023-10-24 Tailoring Risperidone-Loaded Glycethosomal In Situ Gels Using Box–Behnken Design for Treatment of Schizophrenia-Induced Rats via Intranasal Route Abdallah, Marwa H. El-Horany, Hemat El-Sayed El-Nahas, Hanan M. Ibrahim, Tarek M. Pharmaceutics Article Schizophrenic patients often face challenges with adherence to oral regimens. The study aimed to highlight the potentiality of intranasal ethanol/glycerin-containing lipid-nanovesicles (glycethosomes) incorporated into in situ gels for sustaining anti-psychotic risperidone (RS) release. The Box–Behnken Design (BBD) was followed for in vitro characterization. Glycethosomal-based in situ gels were examined by physical, ex vivo, and in vivo investigations. The ethanol impact on minimizing the vesicle size (VS) and enhancing the zeta potential (ZP) and entrapment efficiency (EE%) of nanovesicles was observed. Glycerin displayed positive action on increasing VS and ZP of nanovesicles, but reduced their EE%. After incorporation into various mucoadhesive agent-enriched poloxamer 407 (P407) in situ gels, the optimized gel containing 20% P407 and 1% hydroxypropyl methyl cellulose-K4M (HPMC-K4M) at a 4:1 gel/glycethosomes ratio showed low viscosity and high spreadability with acceptable pH, gel strength, and mucoadhesive strength ranges. The ethanol/glycerin mixture demonstrated a desirable ex vivo skin permeability of RS through the nasal mucosa. By pharmacokinetic analysis, the optimized gel showed eight-fold and three-fold greater increases in RS bioavailability than the control gel and marketed tablet, respectively. Following biochemical assessments of schizophrenia-induced rats, the optimized gel boosted the neuroprotective, anti-oxidant, and anti-inflammatory action of RS in comparison to other tested preparations. Collectively, the intranasal RS-loaded glycethosomal gel offered a potential substitute to oral therapy for schizophrenic patients. MDPI 2023-10-24 /pmc/articles/PMC10675145/ /pubmed/38004501 http://dx.doi.org/10.3390/pharmaceutics15112521 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Abdallah, Marwa H. El-Horany, Hemat El-Sayed El-Nahas, Hanan M. Ibrahim, Tarek M. Tailoring Risperidone-Loaded Glycethosomal In Situ Gels Using Box–Behnken Design for Treatment of Schizophrenia-Induced Rats via Intranasal Route |
title | Tailoring Risperidone-Loaded Glycethosomal In Situ Gels Using Box–Behnken Design for Treatment of Schizophrenia-Induced Rats via Intranasal Route |
title_full | Tailoring Risperidone-Loaded Glycethosomal In Situ Gels Using Box–Behnken Design for Treatment of Schizophrenia-Induced Rats via Intranasal Route |
title_fullStr | Tailoring Risperidone-Loaded Glycethosomal In Situ Gels Using Box–Behnken Design for Treatment of Schizophrenia-Induced Rats via Intranasal Route |
title_full_unstemmed | Tailoring Risperidone-Loaded Glycethosomal In Situ Gels Using Box–Behnken Design for Treatment of Schizophrenia-Induced Rats via Intranasal Route |
title_short | Tailoring Risperidone-Loaded Glycethosomal In Situ Gels Using Box–Behnken Design for Treatment of Schizophrenia-Induced Rats via Intranasal Route |
title_sort | tailoring risperidone-loaded glycethosomal in situ gels using box–behnken design for treatment of schizophrenia-induced rats via intranasal route |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10675145/ https://www.ncbi.nlm.nih.gov/pubmed/38004501 http://dx.doi.org/10.3390/pharmaceutics15112521 |
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