Assessment of PLGA-PEG-PLGA copolymer hydrogel for sustained drug delivery in the ear.
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.
Liang
L
Feng
Jonette A
JA
Ward
S Kevin
SK
Li
Gaurav
G
Tolia
Jinsong
J
Hao
3225 Eden Avenue, Rm 136 HPB, University of Cincinnati, Cincinnati, OH 45267-0004, USA. kevin.li@uc.edu.
Daniel I
DI
Choo
D000818:Animals; D003692:Delayed-Action Preparations; D007758:Ear, Inner / Q000187:drug effects; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D006168:Guinea Pigs; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D011098:Polyglactin 910 / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D012995:Solubility
D003692:Delayed-Action Preparations; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011098:Polyglactin 910; D011092:Polyethylene Glycols