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Naltrexone microspheres: in vitro release and effect on morphine analgesia in mice
1National Pharmaceutical Engineering Research Center, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China. ghe@mail.mdanderson.org
Aim:
To study in vitro release and in vivo effect of four different types of sustained-release naltrexone microspheres on morphine analgesia.
Methods:
Release of naltrexone from four types of biodegradable microspheres was investigated by HPLC. Their antagonist effects on morphine analgesia were observed using mouse hot-plate procedure.
Results:
Poly latide-co-glycolide (PLGA) composition had a remarkable effect on naltrexone release from microspheres and its antagonism towards morphine analgesia. Two formulations of PLGA 50:50 formulation released more than 80 % of total naltrexone and lost their antagonism by 8 d. The PLGA 75:25 formulation with 20 % and 30 % drug loadings did not release 95 % of total drug and lose antagonism until 40 d and 30 d, respectively. Increasing the drug loading enhanced naltrexone release from microspheres and seemed to shorten the analgesic antagonistic effect of naltrexone.
Conclusion:
Antagonism by naltrexone microspheres towards morphine analgesia correlates well with the drug release in vitro.
Insights
Sustained-release naltrexone microspheres show varying effects on morphine analgesia. Poly(lactic-co-glycolic acid) composition and drug loading influence naltrexone release and its antagonism duration.
Area of Science:
- Pharmacology
- Drug Delivery Systems
- Biomaterials
Background:
- Naltrexone is an opioid antagonist.
- Sustained-release formulations aim to improve therapeutic outcomes.
- Understanding drug release kinetics is crucial for efficacy.
Purpose of the Study:
- To evaluate in vitro naltrexone release from biodegradable microspheres.
- To assess the in vivo effect of these microspheres on morphine analgesia.
- To correlate in vitro release with in vivo antagonist effects.
Main Methods:
- High-performance liquid chromatography (HPLC) for drug release quantification.
- Mouse hot-plate test to measure antianalgesic effects.
- Utilized four distinct biodegradable microsphere formulations.
Main Results:
- Poly(lactic-co-glycolic acid) (PLGA) composition significantly impacted naltrexone release and antagonism.
- PLGA 50:50 formulations showed rapid release (>80%) and lost antagonism by 8 days.
- PLGA 75:25 formulations with higher drug loading demonstrated prolonged antagonism (30-40 days).
Conclusions:
- In vitro naltrexone release kinetics from microspheres directly correlate with in vivo antagonism of morphine analgesia.
- Microsphere formulation, specifically PLGA ratio and drug loading, dictates the duration of naltrexone's antagonist effect.