A novel cationic nanostructured lipid carrier for improvement of ocular bioavailability: Design, optimization, in vitro and in vivo evaluation

The objective of this study was to prepare, optimize and evaluate a novel cationic nanostructured lipid carrier (CNLC) system, which can enhance the ophthalmic bioavailability of curcumin (CUR). CUR-loaded CNLC (CUR-CNLC) was prepared using a film-ultrasonic technique. A three-level Box-Behnken design was applied for optimization. The physicochemical properties, in vitro release and corneal permeation of the delivery method were evaluated. Preocular retention capacity study was conducted using a non-invasive fluorescence imaging system. Finally, a pharmacokinetic study in the aqueous humor was performed using a microdialysis technique. The optimal formulation had a mean particle size of 158.1 nm with a homogeneous distribution, a positive surface charge of 36.5 mV, a high entrapment efficiency of 99.12% and drug loading of 1.677%. Transmission electron microscope (TEM) morphology depicted a spherical morphology, and differential scanning calorimetry (DSC) indicated an imperfect crystalline lattice for the formulation. The CUR-CNLC formulation exhibited a sustained drug release and a 1.25-fold increase in in vitro corneal permeation (P < 0.05). The results from in vivo studies indicated the formulation had a high tolerance and a prolonged drug retention capacity in ocular tissues. A pharmacokinetic study of rabbit aqueous humors demonstrated a 2.36-fold increase in ocular bioavailability compared to a CUR solution (CUR-SOL, P < 0.01). The amphipathic octadecyl-quaternized carboxymethyl chitosan (QACMC) was used as a novel cationic material to prolong the residence time and improve the ocular bioavailability. Therefore, CNLC system is a promising approach for ocular delivery of CUR.

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