Bicontinuous Cubic Phase Lipid Nanoparticles Cubosomes: Formulation, Characterization, and Therapeutic Applications

Cubosomes, also known as bicontinuous cubic phase lipid nanoparticles, have attracted significant attention as advanced drug delivery systems due to their unique structural and functional properties. Conventional drug delivery systems often face challenges such as poor solubility, low bioavailability, instability, and non-specific distribution, which limit therapeutic efficacy. Cubosomes overcome these limitations through their distinctive bicontinuous cubic architecture composed of lipid bilayers and interconnected aqueous channels, enabling the encapsulation of hydrophilic, lipophilic, and amphiphilic drugs within a single carrier system. This review provides a comprehensive overview of cubosomes, including their structure, composition, preparation techniques, characterization methods, and drug loading and release mechanisms. Preparation approaches such as top-down and bottom-up methods are discussed, along with key characterization parameters like particle size, zeta potential, morphology, and internal structure analysis. The controlled and sustained drug release from cubosomes, governed by diffusion and partition mechanisms, enhances therapeutic outcomes and reduces dosing frequency. Additionally, cubosomes demonstrate broad applications across various routes of administration, including oral, topical, ocular, transdermal, and parenteral delivery. Their emerging roles in gene delivery, vaccine delivery, and combination therapies further highlight their versatility. Despite certain challenges related to stability, scale-up, and production costs, ongoing advancements in formulation strategies and manufacturing technologies are expected to address these limitations. Overall, cubosomes represent a promising platform for next-generation drug delivery systems and personalized medicine. Keywords: Cubosomes, bicontinuous cubic phase, lipid nanoparticles, drug delivery systems, controlled release, bioavailability.