title: Biomimetic contact lenses eluting olopatadine for allergic conjunctivitis.
abstract: Combination of the ability of contact lenses (CLs) to act as a physical barrier against airborne antigen and to serve as a sustained depot of antihistaminic drugs may improve the efficiency of treatments of some ocular allergic diseases. The aim of this work was to develop CLs that exhibit affinity to olopatadine by mimicking the composition of the natural H1-receptor for which olopatadine behaves as a selective antagonist. Functional monomers that match the chemical groups of the receptor and application of the molecular imprinting technology led to hydrogels able to load high amounts of olopatadine and to sustain the release once in contact with lachrymal fluid. Optimized hydrogels prepared with acrylic acid, 2-acrylamido-2-methyl-1-propanesulfonic acid and benzylmethacrylate as functional monomers provided in few hours olopatadine concentrations similar to those of commercially available eye drops but the levels could be sustained for a whole day, demonstrating their efficacy. Olopatadine-loaded CLs successfully passed the HET-CAM test of ocular irritancy and showed good compatibility with mast cells. They were able to inhibit the release of histamine and TNF-α from sensitized mast cells, proving their potential application in preventing and treating allergic conjunctivitis.
  
  
  
  Contact lenses (CLs) with affinity for antiallergic drugs may constitute an advantageous alternative to eye drops in management of ocular allergies for both contact lens wearers and patients who eventually use neutral CLs as therapeutic platforms. The present work represents a step forward in the state of the art of drug-CL combo products by (i) mimicking the composition of the human receptor of the drug, (ii) exploring combinations of functional monomers that include a monomer (2-acrylamido-2-methyl-1-propanesulfonic acid; AMPSA) with a strong acid group (pKa<4) able to enhance the interaction of the network with olopatadine in the saline environment of the lachrymal fluid, and (iii) analysing in detail the antihistamic effects provided by olopatadine released from the CLs on sensitized mast cells.
authors.affiliation: Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: González-Chomón
authors.affiliation: Instituto de Ortopedia y Banco de Tejidos Musculoesqueléticos, Universidade de Santiago de Compostela, 15872 Santiago de Compostela, Spain.
authors.forename: Maite
authors.initials: M
authors.lastname: Silva
authors.affiliation: Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Concheiro
authors.affiliation: Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain. Electronic address: carmen.alvarez.lorenzo@usc.es.
authors.forename: Carmen
authors.initials: C
authors.lastname: Alvarez-Lorenzo
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D040761:Biomimetic Materials / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002645:Chickens; D003233:Conjunctivitis, Allergic / Q000188:drug therapy* / Q000473:pathology; D003261:Contact Lenses; D065546:Drug Liberation; D006632:Histamine / Q000378:metabolism; D020100:Hydrogels / Q000138:chemical synthesis / Q000737:chemistry; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects; D008422:Materials Testing; D051379:Mice; D054802:Molecular Imprinting; D000069605:Olopatadine Hydrochloride / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000596:Amino Acids; D020100:Hydrogels; D014409:Tumor Necrosis Factor-alpha; D000069605:Olopatadine Hydrochloride; D006632:Histamine
keywords: Allergic conjunctivitis; Antihistaminic effect; Bioinspired contact lens; Controlled drug release; Molecular imprinting; Olopatadine