Antinociceptive effects of hydromorphone, bupivacaine and biphalin released from PLGA polymer after intrathecal implantation in rats

Date

2003-05-01

Author

Sendil, D
Bonney, IM
Carr, DB
Lipkowski, AW
Wise, DL
Hasırcı, Vasıf Nejat

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

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Intraspinal drug delivery, based on the concept of controlling pain by delivering drug to a nociceptive target rich in opioid and other relevant receptors is increasingly used clinically. The therapeutic ratio for opioids or other centrally acting agents is potentially greater if they are administered intrathecally (i.t.) than outside the central nervous system (CNS). The present study was designed with the ultimate goal of formulating a controlled release system for intrathecal analgesia characterized by effectiveness, rapid onset and few side effects for chronic pain control. A biodegradable copolymer poly(L-lactide-co-glycolide) (PLGA) was used to prepare a rod-shaped drug delivery system containing hydromorphone (HM), bupivacaine (BP), both HM and BP, or biphalin (131). In vitro drug release kinetics of these systems showed a zero-order release rate for HM and BP from PLGA (85:15) rods. Drug-loaded rods were implanted i.t. Control groups received only placebo implants. Measurement of analgesic efficacy was carried out with tail flick and paw-withdrawal tests. In vivo studies showed potent, prolonged analgesia in comparison to controls for all active treatments. Analgesic synergy was observed with HM and BP. With further refinements of drug release rate, these rods may offer a clinically relevant alternative for intrathecal analgesia.

Subject Keywords

PLGA, Polymer rod, Hydromorphone, Bupivacaine, Biphalin, Intrathecal drug delivery

URI

https://hdl.handle.net/11511/31147

Journal

BIOMATERIALS

DOI

https://doi.org/10.1016/s0142-9612(02)00567-7

Collections

Graduate School of Natural and Applied Sciences, Article

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Citation Formats

D. Sendil, I. Bonney, D. Carr, A. Lipkowski, D. Wise, and V. N. Hasırcı, “Antinociceptive effects of hydromorphone, bupivacaine and biphalin released from PLGA polymer after intrathecal implantation in rats,” BIOMATERIALS, pp. 1969–1976, 2003, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/31147.