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1.
Int J Pharm ; 585: 119506, 2020 Jul 30.
Article in English | MEDLINE | ID: mdl-32512224

ABSTRACT

A layer-by-layer (LbL) coating was designed using ionic polysaccharides (chitosan, sodium alginate, sodium hyaluronate) and genipin (crosslinker), to sustain the release of diclofenac sodium salt (DCF) from soft contact lens (SCL) materials. The coating was hydrophilic, biocompatible, non-toxic, reduced bacterial growth and had minor effects on the physical properties of the material, such as wettability, ionic permeability, refractive index and transmittance, which remained within the recommended values for SCLs. The coating was applied on a silicone-based hydrogel and on commercial SofLens and Purevision SCLs. The coating attenuated the initial drug burst and extended the therapeutic period for, at least, two weeks. Relevantly, the problems of sterilizing drug loaded SCLs coated with biopolymers, using classic methods that involve high temperature or radiation, were successfully solved through high hydrostatic pressure (HHP) sterilization.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Contact Lenses, Hydrophilic , Diclofenac/administration & dosage , Hydrogels/chemistry , Polyhydroxyethyl Methacrylate/analogs & derivatives , Technology, Pharmaceutical/methods , Alginates/adverse effects , Alginates/chemistry , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/pharmacology , Bacteriological Techniques , Cell Line , Chitosan/adverse effects , Chitosan/chemistry , Delayed-Action Preparations , Diclofenac/adverse effects , Diclofenac/pharmacology , Drug Liberation , Hyaluronic Acid/adverse effects , Hyaluronic Acid/chemistry , Hydrogels/adverse effects , Iridoids/adverse effects , Iridoids/chemistry , Polyhydroxyethyl Methacrylate/adverse effects , Polyhydroxyethyl Methacrylate/chemistry , Wettability
2.
Int J Pharm ; 553(1-2): 186-200, 2018 Dec 20.
Article in English | MEDLINE | ID: mdl-30342082

ABSTRACT

In this study we investigated the possibility of using polyelectrolytes with antibacterial properties to form layer-by-layer (LbL) coatings on contact lens materials with the objective of controlling the release of ophthalmic drugs, while minimizing bacterial growth. A silicone-based hydrogel recently proposed by our group was chosen as a drug releasing soft contact lens (SCL) material and three drugs were tested: moxifloxacin hydrochloride (MXF), chlorhexidine diacetate monohydrate (CHX), and diclofenac sodium salt (DIC). Employed coatings involved combinations of sodium alginate (ALG), chitosan (CHI), sodium hyaluronate (HA) and polylysine hydrobromide (PLL), using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) as a cross-linking agent. Controlled release of DIC was achieved using two double layers of the following combinations: ALG/PLL (EDC), HA (EDC)/CHI and HA/PLL (EDC) + Drug. Furthermore, the physical properties of the coated lens material were kept, or even improved, and bacterial growth was reduced. In contrast, these coatings did not retard the release of MXF and CHX. The specificity of the barrier effect of these LbL films for DIC may be attributed to the formation of reversible interactions between DIC and the polyelectrolyte chains. A top layer of HA was needed to reduce the interaction with tear proteins. The in vivo efficacy of a contact lens coated with ALG/PLL (EDC)//HA and loaded with DIC was predicted using a simplified mathematical model to estimate the drug concentration in the tear fluid. The period of time during which the estimated concentration of DIC remained above the half-maximum inhibitory concentrations for the active enzymes in the process of inflammation, was at least double that obtained with the uncoated sample.


Subject(s)
Anti-Bacterial Agents/pharmacology , Contact Lenses, Hydrophilic , Models, Theoretical , Polyelectrolytes/pharmacology , Administration, Ophthalmic , Anti-Bacterial Agents/chemistry , Chemistry, Pharmaceutical/methods , Chlorhexidine/administration & dosage , Cross-Linking Reagents/chemistry , Delayed-Action Preparations , Diclofenac/administration & dosage , Drug Liberation , Excipients/chemistry , Moxifloxacin/administration & dosage , Polyelectrolytes/chemistry , Tears/metabolism
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