{"doi":"10.1101/2024.04.08.588574","title":"Nor-LAAM loaded PLGA Microparticles for Treating Opioid Use Disorder","abstract":"The treatment landscape for opioid use disorder (OUD) faces challenges stemming from the limited efficacy of existing medications, poor adherence to prescribed regimens, and a heightened risk of fatal overdose post-treatment cessation. Therefore, there is a pressing need for innovative therapeutic strategies that enhance the effectiveness of interventions and the overall well-being of individuals with OUD. This study explored the therapeutic potential of nor-Levo-α-acetylmethadol (nor-LAAM) to treat OUD. We developed sustained release nor-LAAM-loaded poly (lactic-co-glycolic acid) (PLGA) microparticles (MP) using a hydrophobic ion pairing (HIP) approach. The nor-LAAM-MP prepared using HIP with pamoic acid had high drug loading and exhibited minimal initial burst release and sustained release. The nor-LAAM-MP was further optimized for desirable particle size, drug loading, and release kinetics. The lead nor-LAAM-MP (F4) had a relatively high drug loading (11 wt.%) and an average diameter (19 µm) and maintained a sustained drug release for 4 weeks. A single subcutaneous injection of nor-LAAM-MP (F4) provided detectable nor-LAAM levels in rabbit plasma for at least 15 days. We further evaluated the therapeutic efficacy of nor-LAAM-MP (F4) in a well-established fentanyl-addiction rat model, and revealed a marked reduction in fentanyl choice and withdrawal symptoms in fentanyl-dependent rats. These findings provide insights into further developing long-acting nor-LAAM-MP for treating OUD. It has the potential to offer a new effective medication to the existing sparse armamentarium of products available to treat OUD.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":496692,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9549,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":798162,"name":"Chaolong Qin","orcid":"0000-0003-1161-5580","position":1,"is_corresponding":false},{"id":510437,"name":"Tuo Meng","orcid":"0000-0003-4190-2521","position":2,"is_corresponding":false},{"id":1256997,"name":"Aji Alex Moothendathu Raynold","orcid":null,"position":3,"is_corresponding":false},{"id":1064555,"name":"Hadi Sudarjat","orcid":"0000-0003-1379-6135","position":4,"is_corresponding":false},{"id":484959,"name":"E. Andrew Townsend","orcid":"0000-0002-7139-3273","position":5,"is_corresponding":false},{"id":1022822,"name":"Rudra Pangeni","orcid":"0000-0003-2025-676X","position":6,"is_corresponding":false},{"id":704149,"name":"Sagun Poudel","orcid":null,"position":7,"is_corresponding":false},{"id":1256998,"name":"Michelle Arriaga","orcid":null,"position":8,"is_corresponding":false},{"id":1256547,"name":"Long Zhao","orcid":"0000-0002-7655-3029","position":9,"is_corresponding":false},{"id":647607,"name":"Woon N. Chow","orcid":"0000-0003-2745-4291","position":10,"is_corresponding":false},{"id":393444,"name":"Matthew L. Banks","orcid":"0000-0003-4949-5246","position":11,"is_corresponding":false},{"id":332711,"name":"Qingguo Xu","orcid":"0000-0003-3191-0771","position":12,"is_corresponding":false},{"id":1256996,"name":"Diane Ingabire","orcid":null,"position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-19T02:09:27.134858Z","pmid":"38645066","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}