Mucoadhesive chitosan-poly (lactic-co-glycolic acid) nanoparticles for intranasal delivery of quetiapine - Development & characterization in physiologically relevant 3D tissue models
Copyright © 2024 Elsevier B.V. All rights reserved..
Quetiapine hemifumarate (QF) delivery to the CNS via conventional formulations is challenging due to poor solubility and lower oral bioavailability (9 %). Similarly, many other second-generation antipsychotics, such as olanzapine, clozapine, and paliperidone, have also shown low oral bioavailability of <50 %. Hence, the present work was intended to formulate QF-loaded biodegradable PLGA-NPs with appropriate surface charge modification through poloxamer-chitosan and investigate its targeting potential on RPMI-2650 cell lines to overcome the limitations of conventional therapies. QF-loaded poloxamer-chitosan-PLGA in-situ gel (QF-PLGA-ISG) was designed using emulsification and solvent evaporation techniques. Developed QF-PLGA-ISG were subjected to evaluation for particle size, PDI, zeta potential, ex-vivo mucoadhesion, entrapment efficiency (%EE), and drug loading, which revealed 162.2 nm, 0.124, +20.5 mV, 52.4 g, 77.5 %, and 9.7 %, respectively. Additionally, QF-PLGA formulation showed >90 % release within 12 h compared to 80 % of QF-suspension, demonstrating that the surfactant with chitosan-poloxamer polymers could sustainably release medicine across the membrane. Ex-vivo hemolysis study proved that developed PLGA nanoparticles did not cause any hemolysis compared to negative control. Further, in-vitro cellular uptake and transepithelial permeation were assessed using the RPMI-2650 nasal epithelial cell line. QF-PLGA-ISG not only improved intracellular uptake but also demonstrated a 1.5-2-fold increase in QF transport across RPMI-2650 epithelial monolayer. Further studies in the EpiNasal™ 3D nasal tissue model confirmed the safety and efficacy of the developed QF-PLGA-ISG formulation with up to a 4-fold increase in transport compared to plain QF after 4 h. Additionally, histological reports demonstrated the safety of optimized formulation. Finally, favorable outcomes of IN QF-PLGA-ISG formulation could provide a novel platform for safe and effective delivery of QF in schizophrenic patients.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:267 |
|---|---|
| Enthalten in: |
International journal of biological macromolecules - 267(2024), Pt 2 vom: 09. Apr., Seite 131491 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Gadhave, Dnyandev G [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Chitosan/PLGA nanoparticles |
|---|
| Anmerkungen: |
Date Revised 18.04.2024 published: Print-Electronic Citation Status Publisher |
|---|
| doi: |
10.1016/j.ijbiomac.2024.131491 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM370887565 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM370887565 | ||
| 003 | DE-627 | ||
| 005 | 20240419232643.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240411s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.ijbiomac.2024.131491 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1380.xml |
| 035 | |a (DE-627)NLM370887565 | ||
| 035 | |a (NLM)38599435 | ||
| 035 | |a (PII)S0141-8130(24)02296-7 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Gadhave, Dnyandev G |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Mucoadhesive chitosan-poly (lactic-co-glycolic acid) nanoparticles for intranasal delivery of quetiapine - Development & characterization in physiologically relevant 3D tissue models |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 18.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a Copyright © 2024 Elsevier B.V. All rights reserved. | ||
| 520 | |a Quetiapine hemifumarate (QF) delivery to the CNS via conventional formulations is challenging due to poor solubility and lower oral bioavailability (9 %). Similarly, many other second-generation antipsychotics, such as olanzapine, clozapine, and paliperidone, have also shown low oral bioavailability of <50 %. Hence, the present work was intended to formulate QF-loaded biodegradable PLGA-NPs with appropriate surface charge modification through poloxamer-chitosan and investigate its targeting potential on RPMI-2650 cell lines to overcome the limitations of conventional therapies. QF-loaded poloxamer-chitosan-PLGA in-situ gel (QF-PLGA-ISG) was designed using emulsification and solvent evaporation techniques. Developed QF-PLGA-ISG were subjected to evaluation for particle size, PDI, zeta potential, ex-vivo mucoadhesion, entrapment efficiency (%EE), and drug loading, which revealed 162.2 nm, 0.124, +20.5 mV, 52.4 g, 77.5 %, and 9.7 %, respectively. Additionally, QF-PLGA formulation showed >90 % release within 12 h compared to 80 % of QF-suspension, demonstrating that the surfactant with chitosan-poloxamer polymers could sustainably release medicine across the membrane. Ex-vivo hemolysis study proved that developed PLGA nanoparticles did not cause any hemolysis compared to negative control. Further, in-vitro cellular uptake and transepithelial permeation were assessed using the RPMI-2650 nasal epithelial cell line. QF-PLGA-ISG not only improved intracellular uptake but also demonstrated a 1.5-2-fold increase in QF transport across RPMI-2650 epithelial monolayer. Further studies in the EpiNasal™ 3D nasal tissue model confirmed the safety and efficacy of the developed QF-PLGA-ISG formulation with up to a 4-fold increase in transport compared to plain QF after 4 h. Additionally, histological reports demonstrated the safety of optimized formulation. Finally, favorable outcomes of IN QF-PLGA-ISG formulation could provide a novel platform for safe and effective delivery of QF in schizophrenic patients | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Chitosan/PLGA nanoparticles | |
| 650 | 4 | |a EpiNasal™ | |
| 650 | 4 | |a Intranasal delivery | |
| 650 | 4 | |a Monolayer | |
| 650 | 4 | |a Quetiapine | |
| 650 | 4 | |a RPMI-2650 | |
| 650 | 4 | |a Schizophrenia | |
| 700 | 1 | |a Quadros, Mural |e verfasserin |4 aut | |
| 700 | 1 | |a Ugale, Akanksha R |e verfasserin |4 aut | |
| 700 | 1 | |a Goyal, Mimansa |e verfasserin |4 aut | |
| 700 | 1 | |a Ayehunie, Seyoum |e verfasserin |4 aut | |
| 700 | 1 | |a Gupta, Vivek |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International journal of biological macromolecules |d 1992 |g 267(2024), Pt 2 vom: 09. Apr., Seite 131491 |w (DE-627)NLM012627356 |x 1879-0003 |7 nnns |
| 773 | 1 | 8 | |g volume:267 |g year:2024 |g number:Pt 2 |g day:09 |g month:04 |g pages:131491 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.ijbiomac.2024.131491 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 267 |j 2024 |e Pt 2 |b 09 |c 04 |h 131491 | ||