Scalable Manufacturing Method for Model Protein-Loaded PLGA Nanoparticles: Biocompatibility, Trafficking and Release Properties

<b>Background and Objectives</b>: Drug delivery systems (DDSs) offer efficient treatment solutions to challenging diseases such as central nervous system (CNS) diseases by bypassing biological barriers such as the blood–brain barrier (BBB). Among DDSs, polymeric nanoparticles (NPs), part...

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Main Authors: Selin Akpinar Adscheid, Marta Rojas-Rodríguez, Salma M. Abdel-Hafez, Francesco S. Pavone, Marc Schneider, Akif E. Türeli, Martino Calamai, Nazende Günday-Türeli
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/1/87
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author Selin Akpinar Adscheid
Marta Rojas-Rodríguez
Salma M. Abdel-Hafez
Francesco S. Pavone
Marc Schneider
Akif E. Türeli
Martino Calamai
Nazende Günday-Türeli
author_facet Selin Akpinar Adscheid
Marta Rojas-Rodríguez
Salma M. Abdel-Hafez
Francesco S. Pavone
Marc Schneider
Akif E. Türeli
Martino Calamai
Nazende Günday-Türeli
author_sort Selin Akpinar Adscheid
collection DOAJ
description <b>Background and Objectives</b>: Drug delivery systems (DDSs) offer efficient treatment solutions to challenging diseases such as central nervous system (CNS) diseases by bypassing biological barriers such as the blood–brain barrier (BBB). Among DDSs, polymeric nanoparticles (NPs), particularly poly(lactic-co-glycolic acid) (PLGA) NPs, hold an outstanding position due to their biocompatible and biodegradable qualities. Despite their potential, the translation of PLGA NPs from laboratory-scale production to clinical applications remains a significant challenge. This study aims to address these limitations by developing scalable PLGA NPs and evaluating their potential biological applications. <b>Methods</b>: We prepared blank and model-protein-loaded (albumin–FITC and wheat germ agglutinin-488 (WGA-488)) fluorescent PLGA NPs using the traditional double-emulsion method combined with the micro-spray-reactor system, a novel approach that enables fine particle production enabling scale-up applications. We tested the biocompatibility of the NPs in living RPMI 2650 and neuroblastoma cell lines, as well as their trafficking and uptake. Release kinetics of the encapsulated proteins were investigated through confocal microscopy and in vitro release studies, providing insights into the stability and functionality of the released proteins. <b>Results</b>: The formulation demonstrated sustained and prolonged protein release profiles. Importantly, cellular uptake studies revealed that the NPs were not internalized. Furthermore, encapsulated WGA-488 protein retained its functional activity after release, validating the integrity of the encapsulation and release processes. <b>Conclusions</b>: The proof-of-concept study on NP manufacturing and an innovative drug trafficking and release approach can bring new perspectives on scalable preparations of PLGA NPs and their biological applications.
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spelling doaj-art-7f5122aab7e244dbbf23f2f31d6f8db42025-01-24T13:45:54ZengMDPI AGPharmaceutics1999-49232025-01-011718710.3390/pharmaceutics17010087Scalable Manufacturing Method for Model Protein-Loaded PLGA Nanoparticles: Biocompatibility, Trafficking and Release PropertiesSelin Akpinar Adscheid0Marta Rojas-Rodríguez1Salma M. Abdel-Hafez2Francesco S. Pavone3Marc Schneider4Akif E. Türeli5Martino Calamai6Nazende Günday-Türeli7MyBiotech GmbH, Industriestraße 1B, 66802 Überherrn, GermanyEuropean Laboratory for Non-Linear Spectroscopy, via Nello Carrara 1, 50019 Sesto Fiorentino, ItalyDepartment of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, PharmaScienceHub, Saarland University, Campus C4 1, 66123 Saarbrücken, GermanyEuropean Laboratory for Non-Linear Spectroscopy, via Nello Carrara 1, 50019 Sesto Fiorentino, ItalyDepartment of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, PharmaScienceHub, Saarland University, Campus C4 1, 66123 Saarbrücken, GermanyMyBiotech GmbH, Industriestraße 1B, 66802 Überherrn, GermanyEuropean Laboratory for Non-Linear Spectroscopy, via Nello Carrara 1, 50019 Sesto Fiorentino, ItalyMyBiotech GmbH, Industriestraße 1B, 66802 Überherrn, Germany<b>Background and Objectives</b>: Drug delivery systems (DDSs) offer efficient treatment solutions to challenging diseases such as central nervous system (CNS) diseases by bypassing biological barriers such as the blood–brain barrier (BBB). Among DDSs, polymeric nanoparticles (NPs), particularly poly(lactic-co-glycolic acid) (PLGA) NPs, hold an outstanding position due to their biocompatible and biodegradable qualities. Despite their potential, the translation of PLGA NPs from laboratory-scale production to clinical applications remains a significant challenge. This study aims to address these limitations by developing scalable PLGA NPs and evaluating their potential biological applications. <b>Methods</b>: We prepared blank and model-protein-loaded (albumin–FITC and wheat germ agglutinin-488 (WGA-488)) fluorescent PLGA NPs using the traditional double-emulsion method combined with the micro-spray-reactor system, a novel approach that enables fine particle production enabling scale-up applications. We tested the biocompatibility of the NPs in living RPMI 2650 and neuroblastoma cell lines, as well as their trafficking and uptake. Release kinetics of the encapsulated proteins were investigated through confocal microscopy and in vitro release studies, providing insights into the stability and functionality of the released proteins. <b>Results</b>: The formulation demonstrated sustained and prolonged protein release profiles. Importantly, cellular uptake studies revealed that the NPs were not internalized. Furthermore, encapsulated WGA-488 protein retained its functional activity after release, validating the integrity of the encapsulation and release processes. <b>Conclusions</b>: The proof-of-concept study on NP manufacturing and an innovative drug trafficking and release approach can bring new perspectives on scalable preparations of PLGA NPs and their biological applications.https://www.mdpi.com/1999-4923/17/1/87confocal imagingdrug deliverydrug releasedrug traffickingintranasal drug deliverynanoparticles
spellingShingle Selin Akpinar Adscheid
Marta Rojas-Rodríguez
Salma M. Abdel-Hafez
Francesco S. Pavone
Marc Schneider
Akif E. Türeli
Martino Calamai
Nazende Günday-Türeli
Scalable Manufacturing Method for Model Protein-Loaded PLGA Nanoparticles: Biocompatibility, Trafficking and Release Properties
Pharmaceutics
confocal imaging
drug delivery
drug release
drug trafficking
intranasal drug delivery
nanoparticles
title Scalable Manufacturing Method for Model Protein-Loaded PLGA Nanoparticles: Biocompatibility, Trafficking and Release Properties
title_full Scalable Manufacturing Method for Model Protein-Loaded PLGA Nanoparticles: Biocompatibility, Trafficking and Release Properties
title_fullStr Scalable Manufacturing Method for Model Protein-Loaded PLGA Nanoparticles: Biocompatibility, Trafficking and Release Properties
title_full_unstemmed Scalable Manufacturing Method for Model Protein-Loaded PLGA Nanoparticles: Biocompatibility, Trafficking and Release Properties
title_short Scalable Manufacturing Method for Model Protein-Loaded PLGA Nanoparticles: Biocompatibility, Trafficking and Release Properties
title_sort scalable manufacturing method for model protein loaded plga nanoparticles biocompatibility trafficking and release properties
topic confocal imaging
drug delivery
drug release
drug trafficking
intranasal drug delivery
nanoparticles
url https://www.mdpi.com/1999-4923/17/1/87
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