Pain control via opioid analgesic-local anesthetic loaded IPNs.

Abstract:

:Relief of chronic pain is an important clinical problem requiring special care and approaches. The present study was designed for the construction of a controlled release system for local application of analgesics (hydromorphone (HM), morphine (M), and codeine (C)) and a local anesthetic, bupivacaine (BP). An interpenetrating network (IPN) drug release system was prepared by using a biocompatible, biodegradable copolyester, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and another biocompatible but synthetic, nondegradable polymer, poly (2- hydroxyethyl methacrylate), (PHEMA). In situ release kinetics of the IPN system was first order for BP but could not be fitted to any known equation for the other drugs. Complete release from the IPNs occurred within a considerably short time (24 h for 80 % of the drugs) most probably due to the significant hydrophilicity of PHEMA. In order to slow down the release rate these IPNs were coated with PHBV. Release from these coated IPNs (cIPN) resulted in rates that could be described by Higuchi's equations. In vivo measurement of antinociceptive efficacy was carried out in rats with tail flick and paw-withdrawal tests after inducing chronic pain created by sciatic nerve ligation at the right side. Control groups received placebo implants. In vivo studies showed potent, prolonged (2-3 days) antinociception at the site of injury (right paw) for strong opioids (HM and M) and about 2 days for the weak opioid (C) and local anesthetic (BP). In all cases the release rate was found to be as important as the antinociceptive potency. The weakest opioid analgesic of those evaluated (C) had a higher first day antinociception than its stronger counterpart M, probably due to its higher initial concentration that was expected from its faster release rate in the in situ experiments.

journal_name

Curr Drug Deliv

journal_title

Current drug delivery

authors

Keskin DS,Wise DL,Hasirci V

doi

10.2174/1567201043480081

keywords:

subject

Has Abstract

pub_date

2004-01-01 00:00:00

pages

57-64

issue

1

eissn

1567-2018

issn

1875-5704

journal_volume

1

pub_type

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