Influence of Irradiation Sterilization on Polymers Used as Drug Carriers—A Review

Sintzel, Martina Barbara; Merkli, Alain; Tabatabay, C.; Gurny, Robert

doi:10.3109/03639049709148693

Cited by 99 publications

(40 citation statements)

References 81 publications

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“…The prolongation of antigen presentation by hMoDC awarded by antigen delivery via PLGA-MS may improve the efficacy of immunotherapy and certainly deserves to be tested in clinical trials. A so far unsolved problem along this avenue is the sterilization of antigen containing PLGA-MS because g-irradiation has been shown to alter the release properties of PLGA-MS, and it may partially destroy encapsulated antigens [26,27]. Whether the g-irradiation of PLGA-MS prior to hMoDC uptake interferes with antigen presentation to T cells remains to be tested.…”

Section: Discussionmentioning

confidence: 99%

PLGA microspheres for improved antigen delivery to dendritic cells as cellular vaccines

Waeckerle-Men

Groettrup

2005

Advanced Drug Delivery Reviews

178

117

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Dendritic cells (DC) are currently employed as cellular vaccines in clinical trials of tumor immunotherapy. In most trials, peptide epitopes derived from tumor antigens are being exogenously loaded onto human DC for binding to MHC class I molecules. While this is a convenient method, it suffers from the drawback that the persistence of class I/peptide complexes on the cell surface is in the order of a few hours. This drawback limits the success of vaccination. We have investigated biodegradable poly(d,l-lactide-co-glycolide) microspheres (PLGA-MS) as delivery tools for antigen loading of human monocyte-derived DC (hMoDC). Immature hMoDC readily take up PLGA-MS and present epitopes from encapsulated proteins or peptides both on MHC class I and class II. Interestingly, antigen presentation by hMoDC was markedly prolonged when hMoDC were charged with PLGA-MS-encapsulated as opposed to soluble antigens. The properties of hMoDC with respect to migration, cytokine secretion, survival and allostimulation were not adversely affected by the uptake of PLGA-MS. In this article, we will review the properties of PLGA-MS as an adjuvant and summarize recent data on their potential for antigen delivery to dendritic cells.

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Section: Discussionmentioning

confidence: 99%

PLGA microspheres for improved antigen delivery to dendritic cells as cellular vaccines

Waeckerle-Men

Groettrup

2005

Advanced Drug Delivery Reviews

178

117

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“…The alkyl free radicals in the amorphous domains react with oxygen to form peroxyl free radicals. The peroxyl radicals cause chain scissions, within the amorphous region and the crystal domain surface, through hydrogen abstraction (2). Since the Mn reduction (%) of the multiblock copolymers was bigger than the Mw reduction at all the irradiation doses, it could be possible to suppose that degradation reaction …”

Section: Effects Of Irradiation Dosesmentioning

confidence: 99%

“…Because each polymer reacts differently to ionizing radiation, it is important to verify that the maximum dose administered during the sterilization process does not adversely affect the quality, the safety and the performance of the product throughout its shelf life. It is well-known that radiosterilization introduces structural changes that may be detrimental to the integrity and performance of the polymer or polymeric system, limiting their useful working life (2)(3)(4). High-energy radiations generally produce radicals, which in turn may produce more radicals through chain scission, chain transfer quench radicals recombination, or cross linking (5-7).…”

Section: Introductionmentioning

confidence: 99%

γ-Irradiation of PEGd,lPLA and PEG-PLGA Multiblock Copolymers: I. Effect of Irradiation Doses

et al. 2008

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Abstract. To evaluate the effects of different gamma irradiation doses on PEGd,lPLA and PEG-PLGA multiblock copolymers. The behaviour of the multiblock copolymers to irradiation was compared to that of PLA, PLGA polymers. PEGd,lPLA, PEG-PLGA, PLA and PLGA polymers were irradiated by using a 60 Co irradiation source at 5, 15, 25 and 50 kGy total dose. Characterization was performed on all samples before and after irradiation, by nuclear magnetic resonance (NMR), infrared absorption spectrophotometry (FTIR) and gel permeation chromatography (GPC). The effect of gamma irradiation on polymer stability was also evaluated. Results of NMR and FTIR suggest an increase in -OH and -COOH groups, attributed to scission reactions induced by irradiation treatment. Data of GPC analysis showed that the weight average molecular weight (Mw) of polymer samples decreased with increasing irradiation dose. The extent of Mw degradation expressed as percentage of Mw reduction was more prominent for polymers with high molecular weight as PEGd,lPLA and PLA. The dominant effect of gamma-irradiation on both polymer samples was chain scission. The multiblock copolymer PEGd,lPLA presented higher sensitivity to irradiation treatment with respect to PLA, likely due to the presence of PEG in the matrix. The effect of gamma irradiation continues over a much longer period of time after gamma irradiation has been performed. It is suggested that the material reacts with oxygen to form peroxyl free radicals, which may further undergo degradation reactions during storage after irradiation.

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“…Dabei kommen allerdings bewährte Sterilisationsverfahren kaum in Betracht, da mit unerwünschten Materialveränderungen gerechnet werden muss. So werden beim Einsatz feuchter oder trockener Hitze thermische oder hydrolytische Abbauprozesse in den Polymeren initiiert [12]. Auch ist der Einsatz spezieller Sterilisationsmethoden problematisch, wie nachfolgend einige Beispiele zeigen: Ethylenoxid oder ß-Strahlen beeinträchtigen die Materialqualität durch Begasungsreste und Erniedrigung des Molekulargewichtes [3].…”

Section: Introductionunclassified

Synthese und genuine Sterilität von linear und sternförmig strukturierten Polyactiden

Bormann¹,

Vogt²,

Jäger³

et al. 2002

BIOmaterialien

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Influence of Irradiation Sterilization on Polymers Used as Drug Carriers—A Review

Cited by 99 publications

References 81 publications

PLGA microspheres for improved antigen delivery to dendritic cells as cellular vaccines

PLGA microspheres for improved antigen delivery to dendritic cells as cellular vaccines

γ-Irradiation of PEGd,lPLA and PEG-PLGA Multiblock Copolymers: I. Effect of Irradiation Doses

Synthese und genuine Sterilität von linear und sternförmig strukturierten Polyactiden

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