Development of Chitosan–Tripolyphosphate Nanoparticles as Glycopeptide Antibiotic Reservoirs and Ex vivo Evaluation for Their Potential to Enhance the Corneal Permeation in Ocular Drug Delivery

Background: The present investigation aimed to prepare Vancomycin-loaded nanoparticles (VAN-NPs) using chitosan (CS) and tripolyphosphate (TPP) besides exploring the effects of changing CS/TPP ratio on the physicochemical properties, corneal permeation, and ocular delivery of the prepared NPs.

Methods: Different pre-formulations were prepared using the modified ionic gelation process, then were characterized in terms of size distribution. Optimized formulations were furtherly evaluated by some characteristic tools such as Fourier-transform infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA). The in vitro antimicrobial efficacy and drug release amounts along with the Ex-vivo corneal permeation of NPs through the sheep cornea were investigated. Quantification was performed using high-performance liquid chromatography.

Results: Spherical and uniformly distributed NPs were developed with a mean particle size varied between 215–290 nm. FTIR spectroscopy confirmed that the CS/TPP cross-linking has taken place without affecting the pharmacologically active moiety of the drug. The obtained zeta potential values were in the range of +34 to +37 mV, which could ensure the stability of formulations. TGA analysis indicated enhanced thermal stability for the encapsulated drug compared to the plain drug. Formulations indicated suitable antimicrobial efficacy while releasing more than 90% of the drug during 24 h. NPs offered a 10-fold enhancement in corneal permeation compared to the drug solution.

Conclusion: Although further in vivo evaluation is still required to completely confirm the efficacy of the formulations, the enhanced release and corneal permeation of the drug suggest that the prepared NPs are suitable for ocular delivery of VAN.