In situ delivery of synthetic preimplantation factor using aldehyde-modified hyaluronic acid hydrogel with immobilized complexes of chondroitin sulfate derivatives

Synthetic preimplantation factor (SPIF) is a promising therapeutic agent for chronic inflammatory diseases like Multiple Sclerosis (MS), but frequent systemic dosing limits patient adherence and therapy efficacy. This study presents an injectable drug delivery system (DDS) using 2 % (w/v) aldehyde-m...

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Main Authors: Tutut Habibah, Andrea Exnerová, Kristina Nešporová, Una FitzGerald, Abhay Pandit, Marek Ingr, Martin Pravda, Vladimír Velebný
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Carbohydrate Polymer Technologies and Applications
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666893925000283
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author Tutut Habibah
Andrea Exnerová
Kristina Nešporová
Una FitzGerald
Abhay Pandit
Marek Ingr
Martin Pravda
Vladimír Velebný
author_facet Tutut Habibah
Andrea Exnerová
Kristina Nešporová
Una FitzGerald
Abhay Pandit
Marek Ingr
Martin Pravda
Vladimír Velebný
author_sort Tutut Habibah
collection DOAJ
description Synthetic preimplantation factor (SPIF) is a promising therapeutic agent for chronic inflammatory diseases like Multiple Sclerosis (MS), but frequent systemic dosing limits patient adherence and therapy efficacy. This study presents an injectable drug delivery system (DDS) using 2 % (w/v) aldehyde-modified hyaluronic acid (HAOX) and chondroitin sulfate (CSOX) to deliver 100 µg of Fluorescein isothiocyanate-modified SPIF (FITC-SPIF). The DDS utilizes electrostatic interactions between the negatively charged sulfate groups of CSOX and the positively charged amino acids of FITC-SPIF for effective entrapment. Key properties were analyzed, including moderate gelation time (193 s), swelling profile (18 %), injectability (27 G needle) and an established relevant release profile (20 μg/daily ± 3) via anomalous diffusion. Increasing CSOX concentration reduced initial burst release by 38 % (0.5 % CSOX) to 78 % (1 % CSOX), extending release time (T50 %) from 50 h (0.5 % CSOX) to 88 h (1 % CSOX). Additionally, the release of FITC-SPIF enhanced TGF-β secretion in THP-1 macrophages, indicating preserved biological activity. These findings highlight the tunable release and mechanical properties achieved by adjusting the HAOX:CSOX ratio, strategically aligning the DDS for targeted MS symptom management. This system potentially simplifies SPIF delivery and enhances therapeutic efficacy.
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spelling doaj-art-f7a5b0f6be104cbeaff38d3daa8ff74f2025-02-04T04:10:38ZengElsevierCarbohydrate Polymer Technologies and Applications2666-89392025-03-019100689In situ delivery of synthetic preimplantation factor using aldehyde-modified hyaluronic acid hydrogel with immobilized complexes of chondroitin sulfate derivativesTutut Habibah0Andrea Exnerová1Kristina Nešporová2Una FitzGerald3Abhay Pandit4Marek Ingr5Martin Pravda6Vladimír Velebný7Contipro a.s. Dolní Dobrouč 401, Dolní Dobrouč, 56102, Czech Republic; Faculty of Technology, Tomas Bata University in Zlín, Vavrečkova 5669, Czech Republic; Corresponding author.Contipro a.s. Dolní Dobrouč 401, Dolní Dobrouč, 56102, Czech RepublicContipro a.s. Dolní Dobrouč 401, Dolní Dobrouč, 56102, Czech RepublicCURAM, Research Ireland Center for Medical Devices, University of Galway, Upper Newcastle, H91 W2TY, IrelandCURAM, Research Ireland Center for Medical Devices, University of Galway, Upper Newcastle, H91 W2TY, IrelandFaculty of Technology, Tomas Bata University in Zlín, Vavrečkova 5669, Czech RepublicContipro a.s. Dolní Dobrouč 401, Dolní Dobrouč, 56102, Czech RepublicContipro a.s. Dolní Dobrouč 401, Dolní Dobrouč, 56102, Czech RepublicSynthetic preimplantation factor (SPIF) is a promising therapeutic agent for chronic inflammatory diseases like Multiple Sclerosis (MS), but frequent systemic dosing limits patient adherence and therapy efficacy. This study presents an injectable drug delivery system (DDS) using 2 % (w/v) aldehyde-modified hyaluronic acid (HAOX) and chondroitin sulfate (CSOX) to deliver 100 µg of Fluorescein isothiocyanate-modified SPIF (FITC-SPIF). The DDS utilizes electrostatic interactions between the negatively charged sulfate groups of CSOX and the positively charged amino acids of FITC-SPIF for effective entrapment. Key properties were analyzed, including moderate gelation time (193 s), swelling profile (18 %), injectability (27 G needle) and an established relevant release profile (20 μg/daily ± 3) via anomalous diffusion. Increasing CSOX concentration reduced initial burst release by 38 % (0.5 % CSOX) to 78 % (1 % CSOX), extending release time (T50 %) from 50 h (0.5 % CSOX) to 88 h (1 % CSOX). Additionally, the release of FITC-SPIF enhanced TGF-β secretion in THP-1 macrophages, indicating preserved biological activity. These findings highlight the tunable release and mechanical properties achieved by adjusting the HAOX:CSOX ratio, strategically aligning the DDS for targeted MS symptom management. This system potentially simplifies SPIF delivery and enhances therapeutic efficacy.http://www.sciencedirect.com/science/article/pii/S2666893925000283HydrogelSynthetic preimplantation factorHyaluronic acid, Chondroitin sulfatePolyelectrolyte complexes
spellingShingle Tutut Habibah
Andrea Exnerová
Kristina Nešporová
Una FitzGerald
Abhay Pandit
Marek Ingr
Martin Pravda
Vladimír Velebný
In situ delivery of synthetic preimplantation factor using aldehyde-modified hyaluronic acid hydrogel with immobilized complexes of chondroitin sulfate derivatives
Carbohydrate Polymer Technologies and Applications
Hydrogel
Synthetic preimplantation factor
Hyaluronic acid, Chondroitin sulfate
Polyelectrolyte complexes
title In situ delivery of synthetic preimplantation factor using aldehyde-modified hyaluronic acid hydrogel with immobilized complexes of chondroitin sulfate derivatives
title_full In situ delivery of synthetic preimplantation factor using aldehyde-modified hyaluronic acid hydrogel with immobilized complexes of chondroitin sulfate derivatives
title_fullStr In situ delivery of synthetic preimplantation factor using aldehyde-modified hyaluronic acid hydrogel with immobilized complexes of chondroitin sulfate derivatives
title_full_unstemmed In situ delivery of synthetic preimplantation factor using aldehyde-modified hyaluronic acid hydrogel with immobilized complexes of chondroitin sulfate derivatives
title_short In situ delivery of synthetic preimplantation factor using aldehyde-modified hyaluronic acid hydrogel with immobilized complexes of chondroitin sulfate derivatives
title_sort in situ delivery of synthetic preimplantation factor using aldehyde modified hyaluronic acid hydrogel with immobilized complexes of chondroitin sulfate derivatives
topic Hydrogel
Synthetic preimplantation factor
Hyaluronic acid, Chondroitin sulfate
Polyelectrolyte complexes
url http://www.sciencedirect.com/science/article/pii/S2666893925000283
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