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Polymer-mediated delivery of vaccines to treat opioid use disorders and to reduce opioid-induced toxicity.

ABSTRACT: Vaccines offer a potential strategy to treat opioid use disorders (OUD) and to reduce the incidence of opioid-related overdoses. Vaccines induce opioid-specific polyclonal antibodies that selectively and effectively bind the target opioid and prevent its distribution across the blood-brain barrier. Because antibody-mediated reduction of drug distribution to the brain reduces drug-induced behavior and toxicity, vaccine efficacy depends on the quantity and quality of the antibody response. This study tested whether polymer-mediated delivery could improve vaccine efficacy against opioids as well as eliminate the need for booster injections normally required for a successful immunization. A series of novel biodegradable biocompatible thermogelling pentablock co-polymers were used to formulate a candidate vaccine against oxycodone in mice and rats. Polymer-based delivery of the anti-oxycodone vaccine was equally or more effective than administration in aluminum adjuvant in generating oxycodone-specific antibodies and in reducing oxycodone-induced effects and oxycodone distribution to the brain in mice and rats. The composition and release kinetics of the polymer formulations determined vaccine efficacy. Specifically, a formulation consisting of three simultaneous injections of the anti-oxycodone vaccine formulated in three different polymers with slow, intermediate, and fast release kinetics was more effective than an immunization regimen consisting of three sequential injections with the vaccine adsorbed on aluminum. The novel three-phased polymer vaccine formulation was effective in blocking oxycodone-induced antinociception, respiratory depression and bradycardia in rats.

SUBMITTER: Gradinati V

PROVIDER: S-EPMC8268746 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundStrategies to curb overprescribing have focused primarily on the prescriber as the point of intervention. Less is known about how to empower patients to use fewer opioids and decrease the quantity of leftover opioids. Previous studies in nonobstetrical populations suggest that patient counseling about appropriate opioid use improves disposal of unused opioids and overall knowledge about opioid use. Less is known about whether counseling reduces opioid use after hospital discharge.ObjectiveThis study examines whether enhanced discharge counseling on optimal analgesic use after cesarean delivery reduces opioid use and improves proper disposal of unused opioids and opioid use knowledge after hospital discharge.Study designWomen who underwent an uncomplicated cesarean delivery were randomized to enhanced counseling on optimal analgesic use or usual care. Enhanced counseling addressed the following 4 points: (1) pain is normal after cesarean delivery; (2) scheduled ibuprofen should be taken to maintain baseline pain control; (3) opioids should be used sparingly and should be tapered over several days; and (4) all unused opioids should be returned to pharmacy or flushed in a toilet. All participants received 30 tablets of 5 mg hydrocodone-acetaminophen and 30 tablets of 600 mg ibuprofen at discharge. They were contacted 14 days later to determine opioid use and location of leftover opioids and to complete a 10-question analgesic strategies quiz with a score of 1 to 10. We estimated that outcome data on 172 women total would provide an 80% power to detect a 30% reduction in postdischarge opioid use with enhanced counseling.ResultsNotably, 79% of eligible women consented to the study and 175 of 196 participants (84 enhanced counseling, 91 usual care) completed the follow-up. Compared with usual care, the enhanced counseling group was more likely to follow recommendations for proper opioid disposal (risk ratio, 2.3; 95% confidence interval, 1.3-3.9). They also scored significantly higher on the analgesic strategies quiz (10 points [interquartile range, 9-10] vs 8 points [interquartile range, 7-9]; P<.001) than the usual care group. Although the enhanced counseling group used less opioids (7.5 tablets [interquartile range, 2-15] vs 10.0 tablets [interquartile range, 2-16]; P=.55) and a smaller proportion of prescribed opioids (25.0% [6.7-50.0] vs 33.3% [6.7-53.3], P=.55) than the usual care group, differences were not statistically significant. There was no statistically significant evidence of interaction between participant education level and any of the study outcomes.ConclusionEnhanced discharge opioid counseling doubled the frequency of participants reporting proper opioid disposal and improved overall knowledge about the risks associated with opioids. This intervention did not decrease opioid use in a population of women with low overall opioid use. These findings highlight possible methods to intervene on the short-term (misuse and diversion) and long-term (persistent opioid use) consequences of overprescribing.

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Polymer-mediated delivery of vaccines to treat opioid use disorders and to reduce opioid-induced toxicity.

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