Pentablock thermoresponsive hydrogels for chemotherapeutic delivery in a pancreatic cancer model

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dc.authoridgumus, nurcan/0000-0001-9989-4590
dc.contributor.authorElsherbeny, Amr
dc.contributor.authorBayraktutan, Hulya
dc.contributor.authorGumus, Nurcan
dc.contributor.authorMccrorie, Phoebe
dc.contributor.authorGarcia-Sampedro, Andres
dc.contributor.authorParmar, Shreeya
dc.contributor.authorRitchie, Alison A.
dc.date.accessioned2025-03-20T09:51:04Z
dc.date.available2025-03-20T09:51:04Z
dc.date.issued2025
dc.departmentİzmir Bakırçay Üniversitesi
dc.description.abstractThe design of biodegradable and thermoresponsive polymeric hydrogels with tuneable properties holds immense promise for localised and sustained drug delivery. In this study, we designed and synthesised a library of novel pentablock copolymers, incorporating poly(d,l-lactide) (PLA) into methoxypoly(ethylene glycol)-poly(epsilon-caprolactone)-methoxypoly(ethylene glycol) (mPEG-PCL-mPEG, or PECE) hydrogels to enhance the hydrolytic degradation and drug release profiles. A pentablock copolymer, methoxypoly(ethylene glycol)-b-poly(d,l lactide)-b-poly(epsilon-caprolactone)-b-poly(d,l lactide)-b-methoxypoly(ethylene glycol) (mPEG-PLA-PCL-PLA-mPEG, or PELCLE), was selected based on its thermoresponsive sol-gel transition behaviour at a physiologically relevant temperature (37 degrees C). Physicochemical characterisation revealed that both PECE and PELCLE hydrogels self-assembled into micellar structures, with PELCLE exhibiting smaller micellar sizes compared to PECE. The incorporation of PLA led to reduced hydrogel stiffness, enhanced degradability, and decreased swelling compared to PECE. In vitro drug release studies demonstrated that both hydrogels exhibited sustained release of various anti-cancer drugs, with PELCLE generally showing slower release kinetics, highlighting its potential for prolonged drug delivery. For potential pancreatic cancer applications, we evaluated the biocompatibility and therapeutic efficacy of PELCLE hydrogels loaded with gemcitabine and oxaliplatin (GEMOX). In vitro and in vivo studies demonstrated safety and some anti-tumour efficacy of GEMOX-loaded PELCLE compared to free drug administration, attributed to enhanced tumour retention and sustained drug release. These findings highlight the potential of the PELCLE hydrogel as a versatile and effective local drug delivery platform for the treatment of pancreatic cancer and other solid tumours, warranting further investigation towards its clinical translation.
dc.description.sponsorshipUniversity of Nottingham [EP/R035563/1, EP/S021434/1, EP/V049291/1]; UKRI/EPSRC; Little Princess Trust [WM150086, 2219]; Royal Society; TUBITAK; University of Nottingham
dc.description.sponsorshipWe thank UKRI/EPSRC for funding [grants EP/R035563/1, EP/S021434/1, EP/V049291/1], the Little Princess Trust in partnership with CCLG and the Royal Society [Wolfson Research Merit Award WM150086 to CA]. UCO is thankful for a fellowship (2219) from the TUBITAK. We acknowledge Dr Patricia Monteiro for expert assistance in polymer synthesis and characterisation. This work was also supported via Anne McLaren fellowship funding from the University of Nottingham (JCA). We also thank Tom Hyde, Esme Ireson and Paul Cooling for expert technical support. The Nanoscale & Macroscale Research Centre (NMRC) is acknowledged for providing the facilities for TEM, SEM, and related analysis.
dc.identifier.doi10.1039/d4bm01629g
dc.identifier.issn2047-4830
dc.identifier.issn2047-4849
dc.identifier.pmid40007258
dc.identifier.scopus2-s2.0-85219029464
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1039/d4bm01629g
dc.identifier.urihttps://hdl.handle.net/20.500.14034/2394
dc.identifier.wosWOS:001432927000001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherRoyal Soc Chemistry
dc.relation.ispartofBiomaterials Science
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20250319
dc.subjectChitosan-Based Hydrogels
dc.subjectDrug-Delivery
dc.subjectRelease
dc.subjectCombination
dc.subjectSystem
dc.subjectPla
dc.titlePentablock thermoresponsive hydrogels for chemotherapeutic delivery in a pancreatic cancer model
dc.typeArticle

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