Temperature sensitive copolymer systems were previously studied using modified diffusion cells in vitro for intratympanic
injection, and the PLGA-PEG-PLGA copolymer systems were found to provide sustained drug delivery for
several days. The objectives of the present study were to assess the safety of PLGA-PEG-PLGA copolymers in intratympanic
injection in guinea pigs in vivo and to determine the effects of additives glycerol and poloxamer in PLGA-PEGPLGA
upon drug release in the diffusion cells in vitro for sustained inner ear drug delivery. In the experiments, the safety
of PLGA-PEG-PLGA copolymers to inner ear was evaluated using auditory brainstem response (ABR). The effects of the
additives upon drug release from PLGA-PEG-PLGA hydrogel were investigated in the modified Franz diffusion cells
in vitro with cidofovir as the model drug. The phase transition temperatures of the PLGA-PEG-PLGA copolymers in the
presence of the additives were also determined. In the ABR safety study, the PLGA-PEG-PLGA copolymer alone did not
affect hearing when delivered at 0.05-mL dose but caused hearing loss after 0.1-mL injection. In the drug release study,
the incorporation of the bioadhesive additive, poloxamer, in the PLGA-PEG-PLGA formulations was found to decrease
the rate of drug release whereas the increase in the concentration of the humectant additive, glycerol, provided the opposite
effect. In summary, the PLGA-PEG-PLGA copolymer did not show toxicity to the inner ear at the 0.05-mL dose and
could provide sustained release that could be controlled by using the additives for inner ear applications.
Keywords: Auditory brainstem response, Cidofovir, Drug delivery, Ear, Hydrogel, Sustained release.
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