Engineered Brimonidine Tartrate Aminosomes as a Mucoadhesive Platform for Sustained Glaucoma Management: Optimization, In Vitro Characterization, and In Vivo Evaluation.

Purpose: The objective of this study was to engineer and optimize a mucoadhesive, positively charged stearylamine-enriched liposomal platform, termed Aminosomes, to circumvent the biophysical barriers limiting the ocular bioavailability of Brimonidine Tartrate (BT), an alpha-2 adrenergic receptor agonist for glaucoma management.

Methods

Aminosomes were synthesized using a tailored ethanol injection technique and optimized via a 32 × 21 full factorial design. Molecular integrity and crystallinity were assessed using Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The mucoadhesive potential was validated through a mucin interaction assay based on zeta potential shifts. In vitro release kinetics were evaluated using the dialysis membrane diffusion technique, while the therapeutic potential and ocular safety were validated through in vivo pharmacodynamic profiling of intraocular pressure (IOP) reduction, alongside comprehensive biocompatibility assessments via Draize irritancy protocol and histopathological examination.

Results

The optimized Aminosomes exhibited nanometric dimensions, monodisperse size distribution, robust positive surface charge, and superior drug loading. FTIR and XRD analyses confirmed the chemical compatibility of the formulation components, as well as the successful encapsulation of BT and its transition to an amorphous state within the lipidic matrix. The mucoadhesion test demonstrated a high binding affinity for mucin. The in vitro release profile demonstrated a sustained-release pattern (78.8% over 12 h). Non-compartmental pharmacodynamic analysis of IOP-reduction data revealed a 2.8-fold increase in AUC0-24h, 3.5-fold extension in t1/2, and 5.2-fold prolongation in mean residence time (MRT) relative to the standard solution.

Conclusions

The optimized Aminosomes demonstrated superior mucoadhesive anchoring, enhanced and sustained therapeutic flux without inducing ocular toxicity, offering a robust strategy for enhancing the pharmacodynamics of BT.