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Sustained Intra-Articular Delivery of Triple Therapeutics Using a Phase-Transition Phospholipid-Based Gel for
1Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, P.R. China.
Purpose:
This study developed a coordinated-delivery phospholipid-based gel for therapeutics with distinct physicochemical properties to overcome the limitations of current monotherapies for gouty arthritis (GA), achieving synergistic therapeutic effects.
Methods:
A phospholipid phase-transition gel (RMU-Gel) was prepared via a stirring method to co-encapsulate three agents with distinct physicochemical properties-resveratrol (Res), meloxicam (Melx), and uricase (URE). The study evaluated its in vitro release behavior, in vivo pharmacokinetics, the synergistic effects of Res and Melx, pharmacodynamics in a rat model of gouty arthritis, as well as the preliminary safety and biodegradability of the drug-loaded phospholipid gel.
Results:
In vitro release results showed that RMU-Gel enabled a slow and prolonged release of the drugs in the release medium. The combination of resveratrol and meloxicam significantly enhanced anti-inflammatory and antioxidant responses. In the rat model, a single dose of RMU-Gel provided therapeutic effects lasting over 7 days, outperforming repeated injections of drug suspensions, with excellent safety and biodegradability.
Conclusion:
RMU-Gel offers a simple yet powerful platform for the coordinated co-delivery of physicochemically diverse agents. Specifically, the major breakthrough of this study is the successful co-encapsulation and sustained co-release of three therapeutics with markedly different physicochemical properties within a single phospholipid gel system, thereby preserving their multi-pathway therapeutic synergy. This provides a promising multifunctional strategy for efficient management of gouty arthritis.
