Abstract
Infectious ocular keratitis is the leading cause of blindness worldwide. Bacterial resistance to classical pharmacological treatments raised the interest of researchers towards antimicrobial peptide (AMP)-based therapy. hLF 1-11, a synthetic antimicrobial peptide derived from the N-terminus of human lactoferrin, proved effective against different bacteria and yeast but, like all proteinaceous materials, it is unstable from chemical, physical, and biological points of view. In this study, new freeze-dried solid matrices containing mucoadhesive polymers were prepared and characterized in terms of rheology, hydration time, bioadhesion, drug content, and in vitro release. The formulation HPMC/T2/HA/hLF 1-11fd was selected for the delivery of hLF 1-11, since it showed good drug recovery and no chemical degradation up to at least 6 months (long-term stability). Furthermore, the HPMC/T2/HA/hLF 1-11fd matrix allowed for the release of the drug in a simulated physiological environment, linked to an optimal hydration time, and the peptide antimicrobial activity was preserved for up to 15 months of storage, a very promising result considering the chemical liability of proteinaceous material. For its properties, the freeze-dried matrix developed in this study could be a good platform for the delivery of antimicrobial peptides in the precorneal area to treat infectious phenomena of the ocular surface.
Highlights
Infectious keratitis is the leading cause of blindness worldwide
The spread of bacterial drug resistance raised the interest of researchers into the development of alternative therapeutic strategies based on antimicrobial peptides (AMPs) [7]
The formulation that showed no degradation phenomena during the manufacturing process, with the best mucoadhesive characteristics and most suitable release profile, was selected to be loaded with the hLF 1-11 target peptide. This final formulation was tested for both long-term chemical stability and antimicrobial activity against Staphylococcus epidermidis, the leading cause of bacterial endophthalmitis and frequently associated with infectious keratitis worldwide [30]
Summary
Infectious keratitis is the leading cause of blindness worldwide. Delayed or inadequate treatment of this infection can lead to corneal perforation, which can evolve into endophthalmitis and complete vision loss. The formulation that showed no degradation phenomena during the manufacturing process, with the best mucoadhesive characteristics and most suitable release profile, was selected to be loaded with the hLF 1-11 target peptide. This final formulation was tested for both long-term chemical stability (for up to 6 and 15 months of storage) and antimicrobial activity against Staphylococcus epidermidis, the leading cause of bacterial endophthalmitis and frequently associated with infectious keratitis worldwide [30]
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