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一种用于少肌症双效治疗的脂质体策略：咖啡因与透明质酸微球的共递送

A Liposomal Strategy for Dual-Action Therapy in Sarcopenia: Co-Delivery of Caffeine and HAMA.

作者信息

Najm Alfred, Bîrcă Alexandra Cătălina, Niculescu Adelina-Gabriela, Alberts Adina, Grumezescu Alexandru Mihai, Gălățeanu Bianca, Beuran Mircea, Gaspar Bogdan Severus, Turculet Claudiu Stefan, Hudiță Ariana

机构信息

Department of Surgery, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari, Sector 5, 050474 Bucharest, Romania.

Emergency Hospital Floreasca Bucharest, 8 Calea Floreasca, Sector 1, 014461 Bucharest, Romania.

出版信息

Int J Mol Sci. 2025 Jun 24;26(13):6031. doi: 10.3390/ijms26136031.

DOI:10.3390/ijms26136031
PMID:40649810
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12249999/
Abstract

The biological complexity of sarcopenia presents a major challenge for therapeutic intervention due to the wide range of degenerative changes it induces in skeletal muscle. This study demonstrates the potential of liposomal controlled release systems to address these challenges by combining two bioactive agents with complementary actions: caffeine (CAF), encapsulated in DMPC-based liposomes, and hyaluronic acid methacrylate (HAMA), encapsulated in DOPC-based liposomes. A hybrid system was also developed to deliver both substances simultaneously, aiming to restore tissue function through combined metabolic, anti-inflammatory, and regenerative effects. The liposomes exhibited nanoscale dimensions, spherical morphology, and intact membrane structure, as confirmed by electron microscopy. DLS analysis indicated good colloidal stability and monodisperse size distribution across all formulations, with improved stability observed in the hybrid system. Drug release studies showed a time-dependent profile, with HAMA releasing rapidly and CAF releasing gradually, supporting a dual-action therapeutic approach tailored to the multifactorial pathology of sarcopenia. The biological assays, performed in an established in vitro sarcopenia model, revealed the potential of liposomes co-delivering caffeine and HAMA to mitigate oxidative stress, preserve mitochondrial function, and reduce apoptosis in HO-damaged myotubes.

摘要

由于肌肉减少症所引发的广泛退行性变化，其生物学复杂性给治疗干预带来了重大挑战。本研究证明了脂质体控释系统通过结合两种具有互补作用的生物活性剂来应对这些挑战的潜力：包裹在基于二肉豆蔻酰磷脂酰胆碱（DMPC）的脂质体中的咖啡因（CAF），以及包裹在基于二油酰磷脂酰胆碱（DOPC）的脂质体中的甲基丙烯酸透明质酸（HAMA）。还开发了一种混合系统来同时递送这两种物质，旨在通过联合代谢、抗炎和再生作用来恢复组织功能。电子显微镜证实，脂质体呈现纳米级尺寸、球形形态和完整的膜结构。动态光散射（DLS）分析表明，所有制剂都具有良好的胶体稳定性和单分散尺寸分布，在混合系统中观察到稳定性有所提高。药物释放研究显示出时间依赖性特征，HAMA快速释放而CAF逐渐释放，支持了一种针对肌肉减少症多因素病理的双作用治疗方法。在已建立的体外肌肉减少症模型中进行的生物学测定表明，共同递送咖啡因和HAMA的脂质体具有减轻氧化应激、维持线粒体功能以及减少过氧化氢（HO）损伤的肌管中细胞凋亡的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/825a/12249999/6a30693a051f/ijms-26-06031-g012.jpg
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