A Novel Vitamin E TPGS-Based Formulation Enhances Chlorhexidine Bioavailability in Corneal Layers

Area of Science:

• Ophthalmology
• Microbiology
• Pharmaceutics

Background:

• Keratitis, a severe corneal inflammation often caused by bacterial infections, poses a significant challenge due to rising antibiotic resistance.
• Current antibiotic treatments for bacterial keratitis are limited by resistance and require frequent, prolonged application due to poor corneal penetration.
• Chlorhexidine gluconate is an effective antimicrobial agent against various pathogens but can cause ocular irritation at higher concentrations and has poor corneal penetration.

Purpose of the Study:

• To develop and evaluate a novel drug delivery system for chlorhexidine to improve its efficacy and safety in treating keratitis.
• To overcome the limitations of conventional chlorhexidine therapy, including poor corneal penetration, irritation, and the growing threat of antibiotic resistance.

Main Methods:

• A novel formulation combining d-alpha-tocopherol polyethylene glycol 1000 succinate with chlorhexidine was developed.
• Drug accumulation in human corneas was quantified using liquid chromatography.
• Antimicrobial activity and cytotoxicity on human cells were assessed.
• Ocular tolerance was evaluated in rabbit eyes.

Main Results:

• The novel formulation demonstrated significantly higher accumulation of chlorhexidine in human corneas compared to conventional methods.
• The formulation exhibited potent antimicrobial activity against relevant pathogens.
• No toxic effects were observed on human cells, and the formulation was well tolerated in rabbit eyes.
• The enhanced delivery system effectively addressed the limitations of standard chlorhexidine treatment.

Conclusions:

• The developed d-alpha-tocopherol polyethylene glycol 1000 succinate-chlorhexidine formulation represents a safe and effective strategy for treating bacterial keratitis.
• This novel approach enhances corneal drug penetration and antimicrobial efficacy, offering a viable alternative to conventional antibiotic therapies and mitigating the risk of antibiotic resistance.