Thermosensitive Nanocomposite Hydrogels for Intravitreal Delivery of Cefuroxime
Endophthalmitis is a rare, but serious, intravitreal inflammatory disorder that can arise after cataract surgery. The intracameral injection of 1 mg cefuroxime (CEF) followed by three-times daily antibiotic topical administration for a week is generally recognized as the routine method of prophylaxi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-10-01
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| Series: | Nanomaterials |
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| Online Access: | https://www.mdpi.com/2079-4991/9/10/1461 |
| _version_ | 1818399426807332864 |
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| author | Simona Sapino Elena Peira Daniela Chirio Giulia Chindamo Stefano Guglielmo Simonetta Oliaro-Bosso Raffaella Barbero Cristina Vercelli Giovanni Re Valentina Brunella Chiara Riedo Antonio Maria Fea Marina Gallarate |
| author_facet | Simona Sapino Elena Peira Daniela Chirio Giulia Chindamo Stefano Guglielmo Simonetta Oliaro-Bosso Raffaella Barbero Cristina Vercelli Giovanni Re Valentina Brunella Chiara Riedo Antonio Maria Fea Marina Gallarate |
| author_sort | Simona Sapino |
| collection | DOAJ |
| description | Endophthalmitis is a rare, but serious, intravitreal inflammatory disorder that can arise after cataract surgery. The intracameral injection of 1 mg cefuroxime (CEF) followed by three-times daily antibiotic topical administration for a week is generally recognized as the routine method of prophylaxis after cataract surgery. This procedure is controversial because of both the low efficacy and the low adherence to therapy by elderly patients. A unique slow release antibiotic intravitreal injection could solve these problems. The objective of the present study was to design ophthalmic nanocomposite delivery systems based on in situ gelling formulations that undergo sol-to-gel transition upon change in temperature to prolong the effect of CEF. Oil in water (O/W) microemulsion (µE) and solid lipid nanoparticles (SLN), obtained with an innovative formulation technology called <i>cold microemulsion dilution</i>, were evaluated as ocular drug delivery systems for CEF. Drug entrapment efficiency up to 80% was possible by esterifying CEF with 1-dodecanol to obtain dodecyl-CEF (dCEF). Both dCEF-loaded SLN and µE were then added with Pluronic®F127 (20% <i>w</i>/<i>v</i>) to obtain a nanocomposite hydrogel-based long acting system. The prepared thermosensitive formulations were evaluated for their physical appearance, drug content, gelation temperature, injectability and rheological properties, in vitro release studies and stability studies. Moreover, cell proliferation assays on human retinal pigment epithelial ARPE-19 cells were performed to evaluate the influence of this innovative system on the cellular viability. In addition, minimal inhibitory concentration (MIC) was assessed for both CEF and dCEF, revealing the need of dCEF hydrolysis for the antimicrobial activity. Although further experimental investigations are required, the physico-chemical characterization of the nanocomposite hydrogels and the preliminary in vitro release studies highlighted the potential of these systems for the sustained release of CEF. |
| first_indexed | 2024-12-14T07:20:30Z |
| format | Article |
| id | doaj.art-ec9e9ee796ec4f8eafb7053f2b8991d1 |
| institution | Directory Open Access Journal |
| issn | 2079-4991 |
| language | English |
| last_indexed | 2024-12-14T07:20:30Z |
| publishDate | 2019-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nanomaterials |
| spelling | doaj.art-ec9e9ee796ec4f8eafb7053f2b8991d12022-12-21T23:11:38ZengMDPI AGNanomaterials2079-49912019-10-01910146110.3390/nano9101461nano9101461Thermosensitive Nanocomposite Hydrogels for Intravitreal Delivery of CefuroximeSimona Sapino0Elena Peira1Daniela Chirio2Giulia Chindamo3Stefano Guglielmo4Simonetta Oliaro-Bosso5Raffaella Barbero6Cristina Vercelli7Giovanni Re8Valentina Brunella9Chiara Riedo10Antonio Maria Fea11Marina Gallarate12Department of Drug Science and Technology, University of Turin, 10125 Turin, ItalyDepartment of Drug Science and Technology, University of Turin, 10125 Turin, ItalyDepartment of Drug Science and Technology, University of Turin, 10125 Turin, ItalyDepartment of Drug Science and Technology, University of Turin, 10125 Turin, ItalyDepartment of Drug Science and Technology, University of Turin, 10125 Turin, ItalyDepartment of Drug Science and Technology, University of Turin, 10125 Turin, ItalySC of Serology, Istituto Zooprofilattico Sperimentale Piemonte Liguria e Valle d’Aosta, 10154 Turin, ItalyDepartment of Veterinary Sciences of Turin, University of Turin, 10095 Turin, ItalyDepartment of Veterinary Sciences of Turin, University of Turin, 10095 Turin, ItalyDepartment of Chemistry, University of Turin, 10125 Turin, ItalyDepartment of Chemistry, University of Turin, 10125 Turin, ItalyDepartment of Surgical Sciences, University of Turin, 10126 Turin, ItalyDepartment of Drug Science and Technology, University of Turin, 10125 Turin, ItalyEndophthalmitis is a rare, but serious, intravitreal inflammatory disorder that can arise after cataract surgery. The intracameral injection of 1 mg cefuroxime (CEF) followed by three-times daily antibiotic topical administration for a week is generally recognized as the routine method of prophylaxis after cataract surgery. This procedure is controversial because of both the low efficacy and the low adherence to therapy by elderly patients. A unique slow release antibiotic intravitreal injection could solve these problems. The objective of the present study was to design ophthalmic nanocomposite delivery systems based on in situ gelling formulations that undergo sol-to-gel transition upon change in temperature to prolong the effect of CEF. Oil in water (O/W) microemulsion (µE) and solid lipid nanoparticles (SLN), obtained with an innovative formulation technology called <i>cold microemulsion dilution</i>, were evaluated as ocular drug delivery systems for CEF. Drug entrapment efficiency up to 80% was possible by esterifying CEF with 1-dodecanol to obtain dodecyl-CEF (dCEF). Both dCEF-loaded SLN and µE were then added with Pluronic®F127 (20% <i>w</i>/<i>v</i>) to obtain a nanocomposite hydrogel-based long acting system. The prepared thermosensitive formulations were evaluated for their physical appearance, drug content, gelation temperature, injectability and rheological properties, in vitro release studies and stability studies. Moreover, cell proliferation assays on human retinal pigment epithelial ARPE-19 cells were performed to evaluate the influence of this innovative system on the cellular viability. In addition, minimal inhibitory concentration (MIC) was assessed for both CEF and dCEF, revealing the need of dCEF hydrolysis for the antimicrobial activity. Although further experimental investigations are required, the physico-chemical characterization of the nanocomposite hydrogels and the preliminary in vitro release studies highlighted the potential of these systems for the sustained release of CEF.https://www.mdpi.com/2079-4991/9/10/1461cefuroximeendophthalmitisnanocomposite thermosensitive hydrogelsvitreous humorocular flow cell |
| spellingShingle | Simona Sapino Elena Peira Daniela Chirio Giulia Chindamo Stefano Guglielmo Simonetta Oliaro-Bosso Raffaella Barbero Cristina Vercelli Giovanni Re Valentina Brunella Chiara Riedo Antonio Maria Fea Marina Gallarate Thermosensitive Nanocomposite Hydrogels for Intravitreal Delivery of Cefuroxime Nanomaterials cefuroxime endophthalmitis nanocomposite thermosensitive hydrogels vitreous humor ocular flow cell |
| title | Thermosensitive Nanocomposite Hydrogels for Intravitreal Delivery of Cefuroxime |
| title_full | Thermosensitive Nanocomposite Hydrogels for Intravitreal Delivery of Cefuroxime |
| title_fullStr | Thermosensitive Nanocomposite Hydrogels for Intravitreal Delivery of Cefuroxime |
| title_full_unstemmed | Thermosensitive Nanocomposite Hydrogels for Intravitreal Delivery of Cefuroxime |
| title_short | Thermosensitive Nanocomposite Hydrogels for Intravitreal Delivery of Cefuroxime |
| title_sort | thermosensitive nanocomposite hydrogels for intravitreal delivery of cefuroxime |
| topic | cefuroxime endophthalmitis nanocomposite thermosensitive hydrogels vitreous humor ocular flow cell |
| url | https://www.mdpi.com/2079-4991/9/10/1461 |
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