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Novel ocular drug delivery systems (NODDSs) remain to be explored to overcome the anatomical and physiological barriers of the eyes. This study was to encapsulate brinzolamide (BRZ)-hydropropyl-β-cyclodextrin (HP-β-CD) inclusion complex (HP-β-CD/BRZ) into nanoliposomes and investigate its potential as one of NODDS to improve BRZ local glaucomatous therapeutic effect. HP-β-CD/BRZ was firstly prepared to enhance the solubility of poorly water-soluble BRZ. The HP-β-CD/BRZ loaded nanoliposomes (BCL) were subsequently constructed by thin-film dispersion method. After the optimization of the ratio of BRZ to HP-β-CD, the optimal BCL showed an average size of 82.29 ± 6.20 nm, ζ potential of -3.57 ± 0.46 mV and entrapment efficiency (EE) of 92.50 ± 2.10% with nearly spherical in shape. The X-ray diffraction (XRD) confirmed the formation of HP-β-CD/BRZ and BCL. The  in vitro  release study of BCL was evaluated using the dialysis technique, and BCL showed moderate sustained release. BCL (1 mg/mL BRZ) showed a 9.36-fold increase in the apparent permeability coefficient and had a sustained and enhanced intraocular pressure reduction efficacy when compared with the commercially available formulation (BRZ-Sus) (10 mg/mL BRZ). In conclusion, BCL might have a promising future as a NODDS for glaucoma treatment.

Nanoliposome-Encapsulated Brinzolamide-hydropropyl-β-cyclodextrin Inclusion Complex: A Potential Therapeutic Ocular Drug-Delivery System