Efficacy of memantine prodrug microemulsion in a Preclinical model of tendinopathy

Abstract

Tendinopathy is a complex musculoskeletal pathology characterized by pain and dysfunction in the tendon. Tendinopathy management includes pharmacological treatments, which, however, have numerous side effects and low efficacy. New pharmacological approaches are essential to overcome these drawbacks.

This study aimed to test the activity of the newly synthesized memantine-prodrug Memit against chronic tendon pain, which releases H₂S and memantine at the therapeutic site, formulated in a microemulsion for peri-tendon administration. Memit (1 % w/w) was successfully formulated in a microemulsion using the titration method, and the recovery was quantified by liquid chromatography. The characterization of the obtained Memit-loaded microemulsion (Memit-ME) by dynamic light scattering and electron microscopy showed the droplets’ homogeneous dimensional dispersion and spherical shape.

The formulation was found to be physically and chemically stable. Additionally, Memit-ME provided a prolonged release of the prodrug, essential to maintaining its retention at the therapeutic site. The formulation was administered in a rat model of tendon damage induced by a single intra-tendon carrageenan injection to evaluate its anti-hyperalgesic and anti-allodynic profile. The study demonstrated that, thanks to its safety profile and effectiveness in significantly reducing spontaneous pain and postural imbalance, the developed Memit-ME represents a promising approach for tendinopathy management.

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Chemicals

Memit was synthesized as previously reported (Sestito et al., 2019). Vitamin E acetate was bought from A.C.E.F. S.p.a. (Piacenza, Italy). Labrasol ALF and transcutol HP were generously gifted from Gattefossé (Saint-Priest, France). All the organic solvents, namely methanol, acetonitrile, and formic acid, were purchased from Merck Life Sciences Srl (Milan, Italy). Ultrapure water was obtained by a synergy Simplicity UV water purification system provided by Merck Life Sciences Srl (Milan, Italy). Phosphotungstic acid (PTA) was from Electron Microscopy Sciences (Hatfield, PA, USA).

Giulia Vanti, Laura Micheli, Lorenzo Di Cesare Mannelli, Clementina Manera, Simona Sestito, Maria Camilla Bergonzi, Simona Rapposelli, Carla Ghelardini, Anna Rita Bilia, Efficacy of memantine prodrug microemulsion in a Preclinical model of tendinopathy, International Journal of Pharmaceutics, 2025, 125823, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2025.125823.

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