Minor pathological changes are induced by naltrexone-poly(DL-lactide) implants in pregnant rats

Area of Science:

• Pharmacology
• Biomaterials Science
• Toxicology

Background:

• Oral naltrexone is effective for alcohol and heroin dependence but suffers from poor patient compliance.
• Sustained-release formulations aim to improve compliance, often utilizing polymer-drug combinations.
• Limited data exist on the tissue reactivity of naltrexone-polymer implants, especially during pregnancy.

Purpose of the Study:

• To assess the histological changes and tissue reactivity associated with a slow-release subcutaneous naltrexone-poly(DL-lactide) implant in pregnant rats.
• To compare the tissue response to active naltrexone implants versus inactive polymer implants.
• To evaluate the biocompatibility and safety of the naltrexone implant for potential use in pregnant individuals.

Main Methods:

• A subcutaneous implant containing naltrexone-poly(DL-lactide) was administered to timed-mated pregnant rats.
• Tissue response was histologically assessed up to 75 days post-implantation.
• Comparison was made between active naltrexone implants and inactive polymer implants.

Main Results:

• Naltrexone induced a dose-dependent, though low-level, chronic inflammatory response.
• Inactive polymer implants showed minimal foreign body reaction, fibrosis, and low-level inflammation.
• The naltrexone-poly(DL-lactide) implant demonstrated good long-term biocompatibility in pregnant rats.

Conclusions:

• The naltrexone-poly(DL-lactide) implant is tolerated in pregnant rats.
• The findings support the potential utility of this implant for managing alcohol and heroin dependence in pregnant humans.
• Further research may reinforce its role in addiction treatment during pregnancy.