Abstract
Pharmaceutical approaches based on nanotechnologies and the development of eye drops composed of the mucoadhesive polymers chitosan and hyaluronic acid are emerging strategies for the efficient treatment of ocular diseases. These innovative nanoparticulate systems aim to increase drugs’ bioavailability at the ocular surface. For the successful development of these systems, the evaluation of mucoahesiveness (the interaction between the ocular delivery system and mucins present on the eye) is of utmost importance. In this context, the aim of the present work was to investigate the mucoadhesivity of a novel nanoparticle eye drop formulation containing an antibiotic (ceftazidime) intended to treat eye infections. Eye drop formulations comprised a polymer (hydroxypropyl) methyl cellulose (HPMC) 0.75% (w/v) in an isotonic solution incorporating chitosan/sodium tripolyphosphate (TPP)-hyaluronic acid-based nanoparticles containing ceftazidime. The viscosity of the nanoparticles, and the gels incorporating the nanoparticles were characterized in contact with mucin at different mass ratios, allowing the calculation of the rheological synergism parameter (∆η). Results showed that at different nanoparticle eye formulation:mucin weight ratios, a minimum in viscosity occurred which resulted in a negative rheological synergism. Additionally, the results highlighted the mucoadhesivity of the novel ocular formulation and its ability to interact with the ocular surface, thus increasing the drug residence time in the eye. Moreover, the in vitro release and permeation studies showed a prolonged drug release profile from the chitosan/TPP-hyaluronic acid nanoparticles gel formulation. Furthermore, the gel formulations were not cytotoxic on ARPE-19 and HEK293T cell lines, evaluated by the metabolic and membrane integrity tests. The formulation was stable and the drug active, as shown by microbiological studies. In conclusion, chitosan/TPP-hyaluronic acid nanoparticle eye drop formulations are a promising platform for ocular drug delivery with enhanced mucoadhesive properties.
Highlights
Ocular infections may threaten vision, and the classically developed drug delivery systems fail to solve the primary problem [1,2]
It can be sterilized in an autoclave, which is a simple, economical, and safe method of easy validation; it presented an adequate viscosity and a Newtonian behavior; the pH value of 7.22 is proximal to that of the lacrimal fluid and the osmolality value around 300 mOsm/kg indicates an isotonic solution; the zeta potential (ZP) measurements revealed that hydroxypropylmethyl cellulose (HPMC) has a non-ionic nature [18]
Seems to be an adequate polymer for use in ocular administration; it has been largely used in ophthalmic solutions as a viscosity enhancer to improve the drug absorption [19,20]
Summary
Ocular infections may threaten vision, and the classically developed drug delivery systems fail to solve the primary problem [1,2]. Pseudomonas aeruginosa is among the principal pathogens responsible for corneal ulcers. Ceftazidime (CFT) is currently the most active cephalosporin available against. P. aeruginosa, and is resistant to various β-lactamases. Ceftazidime undergoes rapid degradation in aqueous solutions, resulting in the opening of the β-lactam ring. Eye drops containing ceftazidime in aqueous solutions are not commercially available [3]. The majority of ophthalmic formulations are administered as eye drops due to their ease of use, safety, and simplicity of formulation. There are several mechanisms in the eye that are responsible for keeping the ocular surface free from foreign substances and for washing off most
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