Next-generation delivery systems for coenzyme Q10: trends in nanovesicles, penetration enhancers, and bioactivity...

Coenzyme Q10 (CoQ10), a lipophilic benzoquinone essential for mitochondrial energy metabolism and intrinsic antioxidant defense, exhibits substantial therapeutic potential in cardiovascular, neurological, dermatological, and metabolic disorders. However, its pronounced hydrophobicity, high molecular weight (863.34 g/mol), thermolability, and extremely poor aqueous solubility significantly limit its oral and topical bioavailability, rendering conventional formulations insufficient for optimal therapeutic outcomes. This review provides a contemporary overview of advanced delivery strategies designed to overcome these limitations, with a primary focus on nano-vesicular drug delivery systems and bioavailability enhancement approaches. The physicochemical and biological characteristics of CoQ10 are discussed to clarify the major barriers restricting its effective administration. Particular emphasis is placed on nano-vesicular platforms, including niosomes, transfersomes, ethosomes, transethosomes, phytosomes, and cubosomes, highlighting their structural attributes, encapsulation efficiency, permeability enhancement, and reported preclinical and clinical outcomes. Additionally, complementary penetration-enhancing approaches, such as chemical permeation enhancers, microneedles, iontophoresis, and biomimetic or hybrid systems, are examined for their role in improving CoQ10 delivery. The relationship between formulation design and biological performance is critically evaluated to provide mechanistic insight into therapeutic enhancement. Available clinical evidence suggests improved systemic absorption and therapeutic efficacy of CoQ10 through lipid-based and nano-vesicular systems, particularly liposomal and phytosomal formulations. Finally, key translational challenges, including formulation stability, biological barriers, manufacturing scalability, and regulatory considerations, are discussed alongside emerging trends such as stimuli-responsive nanocarriers, mitochondria-targeted systems, and computationally guided formulation development. Collectively, these advances highlight the potential of nano-enabled delivery systems to overcome CoQ10 pharmacokinetic limitations and facilitate future clinical translation.