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HERO ID
1987630
Reference Type
Journal Article
Title
Gamma irradiation of active self-healing PLGA microspheres for efficient aqueous encapsulation of vaccine antigens
Author(s)
Desai, KG; Kadous, S; Schwendeman, SP
Year
2013
Is Peer Reviewed?
1
Journal
Pharmaceutical Research
ISSN:
0724-8741
EISSN:
1573-904X
Volume
30
Issue
7
Page Numbers
1768-1778
Language
English
PMID
23515830
DOI
10.1007/s11095-013-1019-2
Web of Science Id
WOS:000320005100006
Abstract
PURPOSE:
To investigate the effect of γ-irradiation of poly(lactic-co-glycolic acid) (PLGA)/Al(OH)₃/0 or 5 wt% diethyl phthalate (DEP) microspheres for active self-healing encapsulation of vaccine antigens.
METHODS:
Microspheres were irradiated with ⁶⁰Co at 2.5 and 1.8 MRad and 0.37 and 0.20 MRad/h. Encapsulation of tetanus toxoid (TT) was achieved by mixing Al(OH)₃-PLGA microspheres with TT solution at 10-38°C. Electron paramagnetic resonance (EPR) spectroscopy was used to examine free radical formation. Glass transition temperature (T(g)) and molecular weight of PLGA was measured by differential scanning calorimetry and gel permeation chromatography, respectively. Loading and release of TT were examined by modified Bradford, amino acid analysis, and ELISA assays.
RESULTS:
EPR spectroscopy results indicated absence of free radicals in PLGA microspheres after γ-irradiation. Antigen-sorbing capacity, encapsulation efficiency, and T(g) of the polymer were also not adversely affected. When DEP-loaded microspheres were irradiated at 0.2 MRad/h, some PLGA pores healed during irradiation and PLGA healing during encapsulation was suppressed. The molecular weight of PLGA was slightly reduced when DEP-loaded microspheres were irradiated at the same dose rate. At the 0.37 MRad/h dose rate, these trends were not observed and the full immunoreactivity of TT was preserved during encapsulation and 1-month release. Gamma irradiation slightly increased TT initial burst release. The small increase in total irradiation dose from 1.8 to 2.5 MRad had insignificant effect on the polymer and microspheres properties analyzed.
CONCLUSIONS:
Gamma irradiation is a plausible approach to provide a terminally sterilized, self-healing encapsulation PLGA excipient for vaccine delivery.
Keywords
active self-healing encapsulation; controlled release; gamma irradiation; PLGA; vaccine antigens
Tags
IRIS
•
Diethyl phthalate (DEP)
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