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Jennifer J. Kang Mieler, Bin Jiang, Victor Perez-Luna, Eric Brey, William F. Mieler; PLGA Nanospheres Encapsulated Within Thermo-responsive Hydrogel For Ocular Delivery Of Dexamethasone Sodium Phosphate. Invest. Ophthalmol. Vis. Sci. 2011;52(14):467.
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Recently developed thermo-responsive hydrogel has been shown to be effective in encapsulating and releasing pharmacological agents and can be utilized as a relatively non-invasive ocular drug delivery system. Utilizing the unique thermo-responsive hydrogel characteristics, the main objective of this study was to incorporate poly(lactide-co-glycolide) (PLGA) nanospheres to create sustained ocular delivery platform for dexamethasone sodium phosphate (DSP).
Thermo-responsive hydrogel was synthesized using poly(N-isopropylacrylamide) (PNIPAAm) and crosslinked with polyethylene glycols-diacrylate (PEG-DA) and 5% A-lysine and 15% NtBAAM. DSP was encapsulated in PLGA nanospheres (50:50, Mw 7K-17K) using oil in water technique. Nanospheres were added to the hydrogel solution prior to addition of the initiators. DSP release profiles at 37ºC from free nanospheres, hydrogel alone and hydrogel entrapped nanospheres were compared. The activity of DSP was evaluated using a fibroblast proliferation assay.
The mean diameter of nanospheres was 192 nm with a low polydispersity index of 0.146. DSP encapsulation efficiency was 39%. Incorporating nanospheres did not alter the characteristics of thermo-responsive hydrogel in terms of volume phase transition temperature or swelling ratio. When DSP was encapsulated in thermo-responsive hydrogel alone, a complete release of DSP occurred within 2 hours. However, DSP released from nanospheres suspended in the hydrogels lasted for 24 hours. DSP released from delivery system also exhibited dose-responsive inhibited proliferative activity of fibroblasts.
DSP can be incorporated into PLGA nanospheres and can be embedded into thermo-responsive hydrogel for localized delivery and active release. The system provides relatively non-invasive delivery options and promising new platform for sustained delivery of dexamethasone sodium phosphate.
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