Design, Optimization, and Characterization of Lactoferrin-Loaded Chitosan/TPP and Chitosan/Sulfobutylether-β-cyclodextrin Nanoparticles as a Pharmacological Alternative for Keratoconus Treatment

Abstract

This research study describes the design, optimization, and characterization of two different types of chitosan-based nanoparticles as novel drug delivery systems of a protein drug, lactoferrin. A preclinical consistent base was obtained for both nanosystems, being considered as the first pharmacological treatment for keratoconus as an alternative to current invasive clinical methods. Both types of nanoparticles were obtained via the ionotropic gelation technique. The size and morphology of the nanoparticles were studied as a function of the preparation conditions. A mean size of 180.73 ± 40.67 nm, a size distribution [polydispersity index (PDI)] of 0.170 ± 0.067, and positive ζ-potential values, ranging from 17.13 to 19.89 mV, were achieved. Lactoferrin was successfully incorporated into both types of nanocarriers. In vitro release profiles showed a lactoferrin enhanced, prolonged, and controlled delivery from the polymeric matrix. These formulations also demonstrated no stability or cytotoxicity problems, as well as appropriate mucoadhesive properties, with a high permanence time in the ocular surface. Thus, both types of nanoparticles may be considered as nanocarriers for the controlled release of lactoferrin as novel topical ophthalmic drug delivery systems.

Ocular Nanomedicine

“…In the anterior eye segment, cationic nanoparticles, such as chitosan/peptide‐decorated polymeric and triblock copolymeric micelles, can interact with the conjunctiva and cornea (with a negatively charged mucin layer) by electrical attraction, thereby prolonging drug retention and promoting nanoformulation permeability. [ 25b,77 ] Conversely, nanoparticles with a negatively charged surface reportedly avoid adhesion to the normal or healthy ocular surface or cells, promoting tear retention time. [ 78 ] In the posterior eye segments, the cellular membranes of retinal cells are characterized by negatively charged phospholipids, while the vitreous consists of a net negative charge.…”

“…[ 90 ] In addition to polymeric PEG decoration, nanocarriers are directly modified with a mucoadhesive molecule, such as chitosan, to functionalize the sulfobutylether‐ β ‐cyclodextrin nanoparticles, tremendously enhancing the ocular controlled drug release with a high retention time and permeability across the ocular surface. [ 77a ]…”

Biochemical and molecular alterations and potential clinical applications of biomarkers in keratoconus

“…[ 113 ] Lactoferrin is reduced in KC tears and epithelium,[ 47 ] and novel delivery of Lactoferrin using nanoparticles in the form of eye drops is being studied. [ 114 ] These can potentially help in reducing the impact of oxidative cell damage and KC progression.…”

The Microstructure, Antibacterial and Antitumor Activities of Chitosan Oligosaccharides and Derivatives

“…Chitosan is the only basic cationic polysaccharide in nature. To date, chitosan has been found to have a variety of biological activities, such as antibacterial [3][4][5], antitumor [6,7], antioxidant [5] and anti-Alzheimer's disease [8,9] activities, and has been used as a drug carrier [10][11][12] or as a prebiotic to promote human health [13]. Chitosan can play a role in medicine and food, but it can also be used to remove pollutants form aqueous environments.…”