Abstract
Abstract
Background: Mesalazine (MSZ) is standard therapy for ulcerative colitis (UC) but is limited by poor aqueous solubility, high dosing requirements, and undesirable systemic side effects.
Objective: This study aimed to formulate and evaluate Hyaluronic Acid (HA)-conjugated MSZ-loaded mixed polymeric nanomicelles to enhance drug solubility, facilitate targeted colonic delivery, and improve overall therapeutic efficacy.
Methods: Polymeric nanomicelles were synthesized utilizing a thin-film hydration. The optimal formulation underwent surface conjugation with HA to target CD44 receptors. Formulations were characterized in vitro and assessed in vivo utilizing an acetic acid-induced UC rat model.
Results: The optimized mixed nanomicelles exhibited a mean particle size of 84.98 nm, an entrapment efficiency of 97.3%, and achieved a 13-fold enhancement in MSZ solubility compared to the pure drug. Successful HA conjugation was verified through FTIR and NMR analyses. In vitro evaluations demonstrated a sustained release profile, achieving complete drug release over 24 hours. In vivo administration of HA-conjugated nanomicelles resulted in significantly accelerated histological and morphological recovery, improved Disease Activity Index, and restored colon length. Crucially, the targeted formulation minimized systemic absorption while achieving nearly a three-fold increase in colonic tissue drug accumulation compared to pure MSZ.
Conclusion: HA-conjugated mixed polymeric nanomicelles provide a highly efficient, targeted delivery platform that successfully overcomes the biopharmaceutical limitations of conventional MSZ for treating UC.
| Intend to be published in the IJPS ? | NO |
|---|---|
| Has the manuscript been published | not published |
