{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:56:45Z","timestamp":1792173405008,"version":"4.4.0"},"reference-count":61,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T00:00:00Z","timestamp":1679961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Industry","award":["FV40377"],"award-info":[{"award-number":["FV40377"]}]},{"name":"Ministry of Industry","award":["DKRVO\u2013RP\/CPS\/2022\/007"],"award-info":[{"award-number":["DKRVO\u2013RP\/CPS\/2022\/007"]}]},{"name":"Ministry of Education, Youth and Sports of the Czech Republic","award":["FV40377"],"award-info":[{"award-number":["FV40377"]}]},{"name":"Ministry of Education, Youth and Sports of the Czech Republic","award":["DKRVO\u2013RP\/CPS\/2022\/007"],"award-info":[{"award-number":["DKRVO\u2013RP\/CPS\/2022\/007"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>A new solution for local anesthetic and antibiotic delivery after eye surgery is presented. A contact lens-shaped collagen drug carrier was created and loaded by Levofloxacin and Tetracaine with a riboflavin crosslinked surface layer, thus impeding diffusion. The crosslinking was confirmed by Raman spectroscopy, whereas the drug release was investigated using UV-Vis spectrometry. Due to the surface barrier, the drug gradually releases into the corneal tissue. To test the function of the carrier, a 3D printed device and a new test method for a controlled drug release, which mimics the geometry and physiological lacrimation rate of the human eye, were developed. The experimental setup with simple geometry revealed that the prepared drug delivery device can provide the prolonged release profile of the pseudo-first-order for up to 72 h. The efficiency of the drug delivery was further demonstrated using a dead porcine cornea as a drug recipient, without the need to use live animals for testing. Our drug delivery system significantly surpasses the efficiency of antibiotic and anesthetic eyedrops that would have to be applied approximately 30 times per hour to achieve the same dose as that delivered continuously by our device.<\/jats:p>","DOI":"10.3390\/ph16040505","type":"journal-article","created":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T07:05:25Z","timestamp":1679987125000},"page":"505","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Controlled Drug Delivery Device for Cornea Treatment and Novel Method for Its Testing"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9090-4681","authenticated-orcid":false,"given":"Pavel","family":"Urb\u00e1nek","sequence":"first","affiliation":[{"name":"Centre of Polymer Systems, Tomas Bata University in Zl\u00edn, Trida Tomase Bati 5678, 76001 Zlin, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7500-7800","authenticated-orcid":false,"given":"Pavol","family":"\u0160uly","sequence":"additional","affiliation":[{"name":"Centre of Polymer Systems, Tomas Bata University in Zl\u00edn, Trida Tomase Bati 5678, 76001 Zlin, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"\u0160ev\u010d\u00edk","sequence":"additional","affiliation":[{"name":"Centre of Polymer Systems, Tomas Bata University in Zl\u00edn, Trida Tomase Bati 5678, 76001 Zlin, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8300-0588","authenticated-orcid":false,"given":"Barbora","family":"Hanul\u00edkov\u00e1","sequence":"additional","affiliation":[{"name":"Centre of Polymer Systems, Tomas Bata University in Zl\u00edn, Trida Tomase Bati 5678, 76001 Zlin, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1016-5170","authenticated-orcid":false,"given":"Ivo","family":"Ku\u0159itka","sequence":"additional","affiliation":[{"name":"Centre of Polymer Systems, Tomas Bata University in Zl\u00edn, Trida Tomase Bati 5678, 76001 Zlin, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5671-1889","authenticated-orcid":false,"given":"Tom\u00e1\u0161","family":"\u0160op\u00edk","sequence":"additional","affiliation":[{"name":"Centre of Polymer Systems, Tomas Bata University in Zl\u00edn, Trida Tomase Bati 5678, 76001 Zlin, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehrdad","family":"Rafat","sequence":"additional","affiliation":[{"name":"LinkoCare Life Sciences AB, 16975 Stockholm, Sweden"},{"name":"NaturaLens AB, 58330 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Stod\u016flka","sequence":"additional","affiliation":[{"name":"Gemini Eye Clinic, U Gemini 360, 76001 Zlin, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"631","DOI":"10.2147\/OPTH.S289359","article-title":"Current Perspectives on Corneal Transplantation","volume":"16","author":"Liu","year":"2022","journal-title":"Clin. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.2147\/OPTH.S219270","article-title":"Boston Type 1 Keratoprosthesis: Updated Perspectives","volume":"14","author":"Nonpassopon","year":"2020","journal-title":"Clin. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.3389\/fmed.2021.770780","article-title":"Artificial Cornea: Past, Current, and Future Directions","volume":"8","author":"Holland","year":"2021","journal-title":"Front. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.preteyeres.2018.11.005","article-title":"Corneal pain and experimental model development","volume":"71","author":"McKay","year":"2019","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1016\/j.addr.2006.07.027","article-title":"Challenges and obstacles of ocular pharmacokinetics and drug delivery","volume":"58","author":"Urtti","year":"2006","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.3109\/10717544.2014.943336","article-title":"Liposomes in topical ophthalmic drug delivery: An update","volume":"23","author":"Agarwal","year":"2014","journal-title":"Drug Deliv."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"120332","DOI":"10.1016\/j.ijpharm.2021.120332","article-title":"Topical drug delivery to the posterior segment of the eye: Thermodynamic considerations","volume":"597","author":"Sripetch","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1908476","DOI":"10.1002\/adfm.201908476","article-title":"Material, Immunological, and Practical Perspectives on Eye Drop Formulation","volume":"30","author":"Bennett","year":"2020","journal-title":"Adv. Funct. Mater."},{"key":"ref_9","first-page":"177","article-title":"Objective evaluation of applying eye drops by elderly patients","volume":"89","year":"2014","journal-title":"Arch. Soc. Espa\u00f1ola Oftalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"996","DOI":"10.3389\/fbioe.2022.913383","article-title":"Recent Advances of Intraocular Lens Materials and Surface Modification in Cataract Surgery","volume":"10","author":"Luo","year":"2022","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"119285","DOI":"10.1016\/j.biomaterials.2019.119285","article-title":"Topical sustained drug delivery to the retina with a drug-eluting contact lens","volume":"217","author":"Ross","year":"2019","journal-title":"Biomaterials"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ijpharm.2018.06.059","article-title":"Contact lenses with dual drug delivery for the treatment of bacterial conjunctivitis","volume":"548","author":"Maulvi","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"120924","DOI":"10.1016\/j.ijpharm.2021.120924","article-title":"Drug delivery to the anterior segment of the eye: A review of current and future treatment strategies","volume":"607","author":"Mofidfar","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.jconrel.2018.05.020","article-title":"A comprehensive review on contact lens for ophthalmic drug delivery","volume":"281","author":"Xu","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Choi, S.W., and Kim, J. (2018). Therapeutic Contact Lenses with Polymeric Vehicles for Ocular Drug Delivery: A Review. Materials, 11.","DOI":"10.3390\/ma11071125"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.jconrel.2015.01.023","article-title":"Sustained drug release by contact lenses for glaucoma treatment\u2014A review","volume":"202","author":"Carvalho","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1097\/ICL.0000000000000184","article-title":"Dry Eye Treatment Based on Contact Lens Drug Delivery: A Review","volume":"42","author":"Fonseca","year":"2016","journal-title":"Eye Contact Lens"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.ejpb.2017.10.016","article-title":"Epalrestat-loaded silicone hydrogels as contact lenses to address diabetic-eye complications","volume":"122","author":"Concheiro","year":"2018","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"89","DOI":"10.2147\/OPTH.S238756","article-title":"Dexamethasone 0.4mg Sustained-Release Intracanalicular Insert in the Management of Ocular Inflammation and Pain Following Ophthalmic Surgery: Design, Development and Place in Therapy","volume":"14","author":"Brooks","year":"2020","journal-title":"Clin. Ophthalmol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.jcrs.2018.09.023","article-title":"Multicenter randomized phase 3 study of a sustained-release intracanalicular dexamethasone insert for treatment of ocular inflammation and pain after cataract surgery","volume":"45","author":"Tyson","year":"2019","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.2147\/OPTH.S361146","article-title":"Real-World Experience with Intracapsular Administration of Dexamethasone Intraocular Suspension 9% for Control of Postoperative Inflammation","volume":"16","author":"McCabe","year":"2022","journal-title":"Clin. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.ijbiomac.2015.12.077","article-title":"Application of Box\u2013Behnken design for preparation of levofloxacin-loaded stearic acid solid lipid nanoparticles for ocular delivery: Optimization, in vitro release, ocular tolerance, and antibacterial activity","volume":"85","author":"Baig","year":"2016","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.jconrel.2020.07.004","article-title":"Topical siRNA delivery to the cornea and anterior eye by hybrid silicon-lipid nanoparticles","volume":"326","author":"Sutera","year":"2020","journal-title":"J. Control. Release"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"20087","DOI":"10.1021\/acsnano.1c07829","article-title":"Microneedle-Mediated Biomimetic Cyclodextrin Metal Organic Frameworks for Active Targeting and Treatment of Hypertrophic Scars","volume":"15","author":"Wu","year":"2021","journal-title":"ACS Nano"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"102212","DOI":"10.1016\/j.nano.2020.102212","article-title":"Co-hybridized composite nanovesicles for enhanced transdermal eugenol and cinnamaldehyde delivery and their potential efficacy in ulcerative colitis","volume":"28","author":"Zhang","year":"2020","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e12338","DOI":"10.1111\/xen.12338","article-title":"Comprehensive evaluation of decellularized porcine corneal after clinical transplantation","volume":"24","author":"Shi","year":"2017","journal-title":"Xenotransplantation"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"46ra61","DOI":"10.1126\/scitranslmed.3001022","article-title":"A biosynthetic alternative to human donor tissue for inducing corneal regeneration: 24-Month follow-up of a phase 1 clinical study","volume":"2","author":"Fagerholm","year":"2010","journal-title":"Sci. Transl. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1167\/iovs.15-18271","article-title":"3D Corneal Shape After Implantation of a Biosynthetic Corneal Stromal Substitute","volume":"57","author":"Ong","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1586\/erd.10.89","article-title":"Biosynthetic corneas: Prospects for supplementing the human donor cornea supply","volume":"8","author":"Lagali","year":"2011","journal-title":"Expert Rev. Med. Devices"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3165","DOI":"10.2147\/OPTH.S325666","article-title":"Safety and Indicative Effectiveness of Porcine Corneal Lenticular Implants in Patients with Advanced Keratoconus and Post Lasik Ectasia: A Retrospective Clinical Study","volume":"15","author":"Ibrahim","year":"2021","journal-title":"Clin. Ophthalmol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1097\/ICO.0000000000002394","article-title":"Sutureless Femtosecond Laser-Assisted Anterior Lamellar Keratoplasty Using a Bioengineered Cornea as a Viable Alternative to Human Donor Transplantation for Superficial Corneal Opacities","volume":"39","author":"Khodaparast","year":"2020","journal-title":"Cornea"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1016\/j.jcrs.2015.11.007","article-title":"Ultraviolet A: Visible spectral absorbance of the human cornea after transepithelial soaking with dextran-enriched and dextran-free riboflavin 0.1% ophthalmic solutions","volume":"41","author":"Lombardo","year":"2015","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jtos.2013.01.002","article-title":"Corneal Crosslinking with Riboflavin and Ultraviolet A. I. Principles","volume":"11","author":"Raiskup","year":"2013","journal-title":"Ocul. Surf."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"McKay, T.B., Priyadarsini, S., and Karamichos, D. (2019). Mechanisms of Collagen Crosslinking in Diabetes and Keratoconus. Cells, 8.","DOI":"10.3390\/cells8101239"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1167\/iovs.09-3738","article-title":"Mechanisms of Corneal Tissue Cross-linking in Response to Treatment with Topical Riboflavin and Long-Wavelength Ultraviolet Radiation (UVA)","volume":"51","author":"Kraft","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/S0002-9394(02)02220-1","article-title":"Riboflavin\/ultraviolet-A-induced collagen crosslinking for the treatment of keratoconus","volume":"135","author":"Wollensak","year":"2003","journal-title":"Am. J. Ophthalmol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1016\/S0886-3350(03)00407-3","article-title":"Stress-strain measurements of human and porcine corneas after riboflavin-ultraviolet-A-induced cross-linking","volume":"29","author":"Wollensak","year":"2003","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"491","DOI":"10.3389\/fbioe.2022.862969","article-title":"Biomechanical Evaluation of Decellularized and Crosslinked Corneal Implants Manufactured From Porcine Corneas as a Treatment Option for Advanced Keratoconus","volume":"10","author":"Wilson","year":"2022","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/jbm.10145","article-title":"Cytotoxicity of glutaraldehyde crosslinked collagen\/poly(vinyl alcohol) films is by the mechanism of apoptosis","volume":"61","author":"Gough","year":"2002","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Islam, M.M., Abusamra, D.B., Chivu, A., Arg\u00fceso, P., Dohlman, C.H., Patra, H.K., Chodosh, J., and Gonz\u00e1lez-Andrades, M. (2021). Optimization of Collagen Chemical Crosslinking to Restore Biocompatibility of Tissue-Engineered Scaffolds. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13060832"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"162","DOI":"10.3390\/jfb4030162","article-title":"Epoxy Cross-Linked Collagen and Collagen-Laminin Peptide Hydrogels as Corneal Substitutes","volume":"4","author":"Koh","year":"2013","journal-title":"J. Funct. Biomater."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"16936","DOI":"10.1038\/s41598-020-73730-9","article-title":"A porous collagen-based hydrogel and implantation method for corneal stromal regeneration and sustained local drug delivery","volume":"10","author":"Xeroudaki","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1021\/acsbiomaterials.5b00396","article-title":"Collagen-Based Artificial Corneal Scaffold with Anti-Infective Capability for Prevention of Perioperative Bacterial Infections","volume":"1","author":"Riau","year":"2015","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9108","DOI":"10.1038\/s41598-022-13146-9","article-title":"Crosslinker-free collagen gelation for corneal regeneration","volume":"12","author":"Islam","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e201800398","DOI":"10.1002\/jbio.201800398","article-title":"Determination of optical parameters of the porcine eye and development of a simulated model","volume":"12","author":"Regal","year":"2019","journal-title":"J. Biophotonics"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Netto, A.R.T., Hurst, J., Bartz-Schmidt, K.-U., Schnichels, S., Rocha, A., Netto, T., Hurst, J., Bartz-Schmidt, K.-U., and Schnichels, S. (2022). Porcine Corneas Incubated at Low Humidity Present Characteristic Features Found in Dry Eye Disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094567"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"109051","DOI":"10.1016\/j.exer.2022.109051","article-title":"Indirectly assessing changes in corneal properties with OCT speckle after crosslinking in porcine eyes","volume":"219","author":"Danielewska","year":"2022","journal-title":"Exp. Eye Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"103211","DOI":"10.1016\/j.jddst.2022.103211","article-title":"Ocular delivery of cyclosporine A using dissolvable microneedle contact lens","volume":"70","author":"Datta","year":"2022","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1076\/ceyr.28.5.319.28681","article-title":"A novel porcine dry eye model system (pDEM) with simulated lacrimation\/blinking system: Preliminary findings on system variability and effect of corneal drying","volume":"28","author":"Choy","year":"2004","journal-title":"Curr. Eye Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/cxo.12128","article-title":"Corneal epithelial cell viability of an ex vivo porcine eye model","volume":"97","author":"Chan","year":"2014","journal-title":"Clin. Exp. Optom."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1097\/ICO.0b013e3180334f78","article-title":"Safety of UVA-riboflavin cross-linking of the cornea","volume":"26","author":"Spoerl","year":"2007","journal-title":"Cornea"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"686630","DOI":"10.3389\/fphar.2021.686630","article-title":"Corneal Cross-Linking: The Evolution of Treatment for Corneal Diseases","volume":"12","author":"Wu","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1038\/s41598-018-38137-7","article-title":"UVA-activated riboflavin promotes collagen crosslinking to prevent root caries","volume":"9","author":"Uemura","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.sbspro.2011.10.049","article-title":"The Relationship Between Dimensions of Anger and Aggression in Contact and Noncontact Sports","volume":"30","author":"Ahmadi","year":"2011","journal-title":"Procedia Soc. Behav. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.molstruc.2014.05.079","article-title":"Chemometric evaluation of temperature-dependent surface-enhanced Raman spectra of riboflavin: What is the best multivariate approach to describe the effect of temperature?","volume":"1075","year":"2014","journal-title":"J. Mol. Struct."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s00216-008-2470-5","article-title":"Towards a nondestructive chemical characterization of biofilm matrix by Raman microscopy","volume":"393","author":"Ivleva","year":"2009","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Suzuki, S., Gerner, P., and Lirk, P. (2018). Local Anesthetics, Elsevier Inc.. [2nd ed.].","DOI":"10.1016\/B978-0-323-48110-6.00020-X"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Haas, D.A., and Quinn, C.L. (2017). Local Anesthetics, Elsevier. [7th ed.].","DOI":"10.1016\/B978-0-323-39307-2.00014-X"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e5176","DOI":"10.1002\/bmc.5176","article-title":"Development and evaluation of a novelty single-step cleanup followed by HPLC-QTRAP-MS\/MS for rapid analysis of tricaine, tetracaine, and bupivacaine in fish samples","volume":"35","author":"Mu","year":"2021","journal-title":"Biomed. Chromatogr."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.jpba.2016.10.008","article-title":"Robust HPLC\u2013MS\/MS method for levofloxacin and ciprofloxacin determination in human prostate tissue","volume":"132","author":"Szerkus","year":"2017","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.clae.2019.04.011","article-title":"Extended delivery of non-steroidal anti-inflammatory drugs through contact lenses loaded with Vitamin E and cationic surfactants","volume":"42","author":"Hu","year":"2019","journal-title":"Contact Lens Anterior Eye"}],"updated-by":[{"DOI":"10.3390\/ph18050720","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T00:00:00Z","timestamp":1679961600000}}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/4\/505\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T14:04:02Z","timestamp":1754229842000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/4\/505"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,28]]},"references-count":61,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["ph16040505"],"URL":"https:\/\/doi.org\/10.3390\/ph16040505","relation":{"correction":[{"id-type":"doi","id":"10.3390\/ph18050720","asserted-by":"object"}]},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,28]]}}}