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Risperidone-Loaded PLGA–Lipid Particles with Improved Release Kinetics: Manufacturing and Detailed Characterization by Electron Microscopy and Nano-CT

For parenteral controlled drug release, the desired zero order release profile with no lag time is often difficult to achieve. To overcome the undesired lag time of the current commercial risperidone controlled release formulation, we developed PLGA–lipid microcapsules (MCs) and PLGA–lipid microgels...

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Autores principales: Janich, Christopher, Friedmann, Andrea, Martins de Souza e Silva, Juliana, Santos de Oliveira, Cristine, de Souza, Ligia E., Rujescu, Dan, Hildebrandt, Christian, Beck-Broichsitter, Moritz, Schmelzer, Christian E. H., Mäder, Karsten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956012/
https://www.ncbi.nlm.nih.gov/pubmed/31835353
http://dx.doi.org/10.3390/pharmaceutics11120665
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author Janich, Christopher
Friedmann, Andrea
Martins de Souza e Silva, Juliana
Santos de Oliveira, Cristine
de Souza, Ligia E.
Rujescu, Dan
Hildebrandt, Christian
Beck-Broichsitter, Moritz
Schmelzer, Christian E. H.
Mäder, Karsten
author_facet Janich, Christopher
Friedmann, Andrea
Martins de Souza e Silva, Juliana
Santos de Oliveira, Cristine
de Souza, Ligia E.
Rujescu, Dan
Hildebrandt, Christian
Beck-Broichsitter, Moritz
Schmelzer, Christian E. H.
Mäder, Karsten
author_sort Janich, Christopher
collection PubMed
description For parenteral controlled drug release, the desired zero order release profile with no lag time is often difficult to achieve. To overcome the undesired lag time of the current commercial risperidone controlled release formulation, we developed PLGA–lipid microcapsules (MCs) and PLGA–lipid microgels (MGs). The lipid phase was composed of middle chain triglycerides (MCT) or isopropylmyristate (IPM). Hydroxystearic acid was used as an oleogelator. The three-dimensional inner structure of Risperidone-loaded MCs and MGs was assessed by using the invasive method of electron microscopy with focused ion beam cutting (FIB-SEM) and the noninvasive method of high-resolution nanoscale X-ray computed tomography (nano-CT). FIB-SEM and nano-CT measurements revealed the presence of highly dispersed spherical structures around two micrometres in size. Drug release kinetics did strongly depend on the used lipid phase and the presence or absence of hydroxystearic acid. We achieved a nearly zero order release without a lag time over 60 days with the MC-MCT formulation. In conclusion, the developed lipid-PLGA microparticles are attractive alternatives to pure PLGA-based particles. The advantages include improved release profiles, which can be easily tuned by the lipid composition.
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spelling pubmed-69560122020-01-23 Risperidone-Loaded PLGA–Lipid Particles with Improved Release Kinetics: Manufacturing and Detailed Characterization by Electron Microscopy and Nano-CT Janich, Christopher Friedmann, Andrea Martins de Souza e Silva, Juliana Santos de Oliveira, Cristine de Souza, Ligia E. Rujescu, Dan Hildebrandt, Christian Beck-Broichsitter, Moritz Schmelzer, Christian E. H. Mäder, Karsten Pharmaceutics Article For parenteral controlled drug release, the desired zero order release profile with no lag time is often difficult to achieve. To overcome the undesired lag time of the current commercial risperidone controlled release formulation, we developed PLGA–lipid microcapsules (MCs) and PLGA–lipid microgels (MGs). The lipid phase was composed of middle chain triglycerides (MCT) or isopropylmyristate (IPM). Hydroxystearic acid was used as an oleogelator. The three-dimensional inner structure of Risperidone-loaded MCs and MGs was assessed by using the invasive method of electron microscopy with focused ion beam cutting (FIB-SEM) and the noninvasive method of high-resolution nanoscale X-ray computed tomography (nano-CT). FIB-SEM and nano-CT measurements revealed the presence of highly dispersed spherical structures around two micrometres in size. Drug release kinetics did strongly depend on the used lipid phase and the presence or absence of hydroxystearic acid. We achieved a nearly zero order release without a lag time over 60 days with the MC-MCT formulation. In conclusion, the developed lipid-PLGA microparticles are attractive alternatives to pure PLGA-based particles. The advantages include improved release profiles, which can be easily tuned by the lipid composition. MDPI 2019-12-09 /pmc/articles/PMC6956012/ /pubmed/31835353 http://dx.doi.org/10.3390/pharmaceutics11120665 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Janich, Christopher
Friedmann, Andrea
Martins de Souza e Silva, Juliana
Santos de Oliveira, Cristine
de Souza, Ligia E.
Rujescu, Dan
Hildebrandt, Christian
Beck-Broichsitter, Moritz
Schmelzer, Christian E. H.
Mäder, Karsten
Risperidone-Loaded PLGA–Lipid Particles with Improved Release Kinetics: Manufacturing and Detailed Characterization by Electron Microscopy and Nano-CT
title Risperidone-Loaded PLGA–Lipid Particles with Improved Release Kinetics: Manufacturing and Detailed Characterization by Electron Microscopy and Nano-CT
title_full Risperidone-Loaded PLGA–Lipid Particles with Improved Release Kinetics: Manufacturing and Detailed Characterization by Electron Microscopy and Nano-CT
title_fullStr Risperidone-Loaded PLGA–Lipid Particles with Improved Release Kinetics: Manufacturing and Detailed Characterization by Electron Microscopy and Nano-CT
title_full_unstemmed Risperidone-Loaded PLGA–Lipid Particles with Improved Release Kinetics: Manufacturing and Detailed Characterization by Electron Microscopy and Nano-CT
title_short Risperidone-Loaded PLGA–Lipid Particles with Improved Release Kinetics: Manufacturing and Detailed Characterization by Electron Microscopy and Nano-CT
title_sort risperidone-loaded plga–lipid particles with improved release kinetics: manufacturing and detailed characterization by electron microscopy and nano-ct
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956012/
https://www.ncbi.nlm.nih.gov/pubmed/31835353
http://dx.doi.org/10.3390/pharmaceutics11120665
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