Cubosome-based nanoformulation of synthesized 1-cyclopentyl benzimidazole: In-vitro characterization and antibacterial evaluation

Background: Despite of having broad spectrum anti-bacterial activity, benzimidazole has limited clinical applications out of low solubility and bioavailability. Benzimidazole and cubosomal delivery systems are individually well studied, their combined application remains limited, particularly for newly designed derivatives with unexplored biological activity. Objective: This study reports the synthesis and characterization of N-cyclopentyl benzimidazole-loaded cubosomes for antibacterial application through improved solubility and controlled release. Methods: The N-cyclopentyl benzimidazole was synthesized by the reaction of benzimidazole with Bromo cyclopentane and confirmed by FT-IR, 1H, and 13C NMR spectroscopy. Cubosome nanoparticles were formed by the homogenization method, using glyceryl monooleate (GMO) as a lipid and poloxamer 407 (P407) as a surfactant. Different co-surfactants like Brij 35 (B 35), Myrj 52 (M 52), Tween 20 (T 20), and polyvinyl alcohol (PVA) as stabilizer were used to optimize the formulations and characterized for size, zeta potential, polydispersity index, entrapment efficiency, in-vitro drug release, and transmission electron microscopy. Results: Among the tested formulations, the cubosome containing 3% PVA demonstrated optimal characteristics, including a nanosize (~128 nm), high drug entrapment efficiency (94.08%), and colloidal stability. The antibacterial activity was assessed against Staphylococcus aureus and Escherichia coli. While the free drug exhibited larger zones of inhibition, the cubosome-encapsulated formulation showed sustained antibacterial effects, attributed to improved aqueous dispersion and prolonged release. Conclusion: These findings highlight the potential of cubosome-based delivery to enhance the solubility and therapeutic efficacy.