TY - JOUR
T1 - Pharmacokinetics and efficacy of a ketorolac-loaded ocular coil in New Zealand white rabbits
AU - Bertens, C.J.F.
AU - Gijs, M.
AU - Dias, A.A.J.
AU - van den Biggelaar, F.J.H.M.
AU - Ghosh, A.
AU - Sethu, S.
AU - Nuijts, R.M.M.A.
N1 - Funding Information:
This research was performed under the framework of the Chemelot Institute for Science and Technology (InSciTe). The authors thank Tos Berendschot Ph.D. and Theo Gorgels Ph.D. from the University Eye Clinic Maastricht for their statistical and methodological input.
Publisher Copyright:
© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - Eye drops are considered standard practice for the delivery of ocular drugs. However, low patient compliance and low drug levels compromise its effectiveness. Our group developed a ketorolac-loaded ocular coil for sustained drug delivery up to 28 days. The aim of this study was to gain insight into the pharmacokinetics and efficacy of the ocular coil. The pharmacokinetics of the ketorolac-loaded ocular coil versus eye drops were tested in New Zealand White rabbits by repetitive sampling for 28 days. Efficacy of the ocular coil was also tested in New Zealand White rabbits. Ocular inflammation was induced where after the ocular coil was inserted, or eye drops, or no treatment was provided. The total protein concentration and cytokine levels were measured in tears, aqueous humor, and plasma at 4 h, 8 h, 24 h, 4 d, 7 d, 14 d, 21 d, and 28 d. Four h after inserting the ocular coil in the eye, ketorolac levels in aqueous humor and plasma were higher in the ocular coil group than in the eye drop group. Ketorolac released from the ocular coil could be detected up to 28 d in tears, up to 4 d in aqueous humor and up to 24 h in plasma. After inducing inflammation, both the ocular coil and eye drops were able to suppress prostaglandin E-2, TNF alpha and IL-6 levels in aqueous humor and plasma as compared to the group that received no treatment. To conclude, the ocular coil facilitated a sustained release of the drug and showed similar therapeutic benefit in suppressing post-operative inflammation as eye drops.
AB - Eye drops are considered standard practice for the delivery of ocular drugs. However, low patient compliance and low drug levels compromise its effectiveness. Our group developed a ketorolac-loaded ocular coil for sustained drug delivery up to 28 days. The aim of this study was to gain insight into the pharmacokinetics and efficacy of the ocular coil. The pharmacokinetics of the ketorolac-loaded ocular coil versus eye drops were tested in New Zealand White rabbits by repetitive sampling for 28 days. Efficacy of the ocular coil was also tested in New Zealand White rabbits. Ocular inflammation was induced where after the ocular coil was inserted, or eye drops, or no treatment was provided. The total protein concentration and cytokine levels were measured in tears, aqueous humor, and plasma at 4 h, 8 h, 24 h, 4 d, 7 d, 14 d, 21 d, and 28 d. Four h after inserting the ocular coil in the eye, ketorolac levels in aqueous humor and plasma were higher in the ocular coil group than in the eye drop group. Ketorolac released from the ocular coil could be detected up to 28 d in tears, up to 4 d in aqueous humor and up to 24 h in plasma. After inducing inflammation, both the ocular coil and eye drops were able to suppress prostaglandin E-2, TNF alpha and IL-6 levels in aqueous humor and plasma as compared to the group that received no treatment. To conclude, the ocular coil facilitated a sustained release of the drug and showed similar therapeutic benefit in suppressing post-operative inflammation as eye drops.
KW - anti-inflammation
KW - ketorolac tromethamine
KW - ocular coil
KW - ocular drug delivery device
KW - pharmacokinetics
KW - sustained drug delivery
KW - Ketorolac tromethamine
U2 - 10.1080/10717544.2021.1883157
DO - 10.1080/10717544.2021.1883157
M3 - Article
C2 - 33594935
SN - 1071-7544
VL - 28
SP - 400
EP - 407
JO - Drug Delivery
JF - Drug Delivery
IS - 1
ER -