TY - JOUR
T1 - Controlled and Extended Release of a Model Protein from a Microsphere-Hydrogel Drug Delivery System
AU - Osswald, Christian R.
AU - Kang-Mieler, Jennifer J.
N1 - Publisher Copyright:
© 2015, Biomedical Engineering Society.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - In extended ocular drug delivery applications, it is necessary to exert control over the release characteristics of the drug. Design considerations must be made to limit the initial burst (IB) and ensure complete release of drug from the drug delivery system (DDS). In this study, ovalbumin was used as a model protein to explore the effects on release of polymer formulation and fabrication technique in poly(lactic-co-glycolic acid) (PLGA) microspheres. Furthermore, the effect on release of suspending these microspheres in an injectable, thermo-responsive poly(N-isopropylacrylamide)-based hydrogel was determined. To characterize release, ovalbumin was radiolabeled with iodine-125. Regardless of polymer formulation or fabrication technique, pulsatile release was achieved with a second burst occurring after ~70 days for microspheres alone. Suspending PLGA 75:25 microspheres within hydrogel reduced the IB by ~75%, delayed the second burst by 28 days, and extended release out to ~200 days with steadier, consistent release throughout compared to microspheres alone. The combined microsphere-hydrogel DDS remains injectable through small-gauge needles and may have many applications, namely ocular drug delivery to the posterior segment.
AB - In extended ocular drug delivery applications, it is necessary to exert control over the release characteristics of the drug. Design considerations must be made to limit the initial burst (IB) and ensure complete release of drug from the drug delivery system (DDS). In this study, ovalbumin was used as a model protein to explore the effects on release of polymer formulation and fabrication technique in poly(lactic-co-glycolic acid) (PLGA) microspheres. Furthermore, the effect on release of suspending these microspheres in an injectable, thermo-responsive poly(N-isopropylacrylamide)-based hydrogel was determined. To characterize release, ovalbumin was radiolabeled with iodine-125. Regardless of polymer formulation or fabrication technique, pulsatile release was achieved with a second burst occurring after ~70 days for microspheres alone. Suspending PLGA 75:25 microspheres within hydrogel reduced the IB by ~75%, delayed the second burst by 28 days, and extended release out to ~200 days with steadier, consistent release throughout compared to microspheres alone. The combined microsphere-hydrogel DDS remains injectable through small-gauge needles and may have many applications, namely ocular drug delivery to the posterior segment.
KW - Hydrogel
KW - Microspheres
KW - Ocular drug delivery
KW - Ovalbumin
KW - Poly(N-isopropylacrylamide)
KW - Poly(lactic-co-glycolic acid)
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U2 - 10.1007/s10439-015-1314-7
DO - 10.1007/s10439-015-1314-7
M3 - Article
C2 - 25835212
AN - SCOPUS:84945482901
SN - 0090-6964
VL - 43
SP - 2609
EP - 2617
JO - Annals of Biomedical Engineering
JF - Annals of Biomedical Engineering
IS - 11
ER -