β-Cyclodextrin-functionalized nanocarriers for bromocriptine: development, evaluation and histopathological studies.

Bromocriptine (BCM), a dopaminergic agonist used in Parkinson's disease treatment, has poor oral bioavailability due to extensive first-pass metabolism and limited gastrointestinal absorption. This study aimed to develop a β-cyclodextrin-functionalized bromocriptine nanoemulsion (oil-in-water) to enhance drug solubility, stability, and bioavailability while facilitating direct brain delivery via the intranasal route. The formulation was designed to overcome systemic metabolic barriers, improve drug permeation across the blood-brain barrier, and ensure sustained therapeutic effects with minimal systemic side effects. Nano-emulsions were prepared using high-shear homogenization. Characterization was performed using scanning electron microscopy (SEM) for morphological analysis. Globule size and zeta potential were measured using Malvern Zetasizer. Fourier Transform Infrared Spectroscopy (FTIR) was used for structural analysis, while X-ray diffraction (XRD) assessed crystallinity. Differential Scanning Calorimetry (DSC) was conducted for thermal analysis. Drug content and drug release were evaluated using UV-visible spectroscopy. Stability studies were performed using centrifugation and freeze-thaw methods. Docking studies and Histopathological evaluation were also performed of the prepared formulations. Morphological studies revealed nano-sized globular particles with a mean diameter of 117.2 nm and a low polydispersity index (PDI 0.810), indicating uniformity. The nanoemulsion exhibited a zeta potential of -10.5 mV, ensuring colloidal stability. The encapsulation efficiency (EE%) of the optimized formulation (F4) was 95.36(% w/w,) with a drug load of approximately 9.5(% w/w). drug release reached 85.65%, with permeation release of 78.44% and 70.13% ex-vivo. The formulation remained stable under freeze-thaw and centrifugation conditions. Cell toxicity assessments demonstrated excellent biocompatibility, with no significant cytotoxic effects observed in histopathological evaluations. This nanoemulsion presents a promising alternative to oral bromocriptine for Parkinson's treatment.