title: A temperature-induced and shear-reversible assembly of latanoprost-loaded amphiphilic chitosan colloids: characterization and in vivo glaucoma treatment.
abstract: Hydrogels composed of assembled colloids is a material class that is currently receiving much interest and shows great promise for use in biomedical applications. This emerging material class presents unique properties derived from the combination of nanosized domains in the form of colloidal particles with a continuous gel network and an interspersed liquid phase. Here we developed an amphiphilic chitosan-based, thermogelling, shear-reversible colloidal gel system for improved glaucoma treatment and addressed how preparation procedures and loading with the anti-glaucoma drug latanoprost and commonly used preservative benzalkonium chloride influenced the mechanical properties of and drug release from the colloidal gels. The results highlight that incorporated substances and preparation procedures have effects both on mechanical properties and drug release, but that the release of drug loaded in the colloidal carriers is mainly limited by transport out of the carriers, rather than by diffusion within the gel. The developed colloidal chitosan based gels hold outstanding biomedical potential, as confirmed by the ease of preparation and administration, low cytotoxicity in MTT assay, excellent biocompatibility and lowering of intraocular pressure for 40 days in a rabbit glaucoma model. The findings clearly justify further investigations towards clinical use in the treatment of glaucoma. Furthermore, the use of this shear-reversible colloidal gel could easily be extended to localized treatment of a number of critical conditions, from chronic disorders to cancer, potentially resulting in a number of new therapeutics with improved clinical performance.
authors.affiliation: Department of Materials Science and Engineering, BioICT Consortium, National Chiao Tung University, 1001 Ta-Hseuh Road, Hsinchu, Taiwan 300, ROC.
authors.forename: Meng-Hsuan
authors.initials: MH
authors.lastname: Hsiao
authors.affiliation: Institute of Pharmacology, National Yang-Ming University and Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan; National Yang-Ming University School of Medicine, No. 155, Sec. 2, Linong Street, Taipei, Taiwan; Department of Ophthalmology, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, Taipei, Taiwan.
authors.forename: Shih-Hwa
authors.initials: SH
authors.lastname: Chiou
authors.affiliation: Ian Wark Research Institute, University of South Australia, Mawson Lakes Campus, Mawson Lakes SA 5095, Australia.
authors.forename: Mikael
authors.initials: M
authors.lastname: Larsson
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei, Taiwan.
authors.forename: Kuo-Hsuan
authors.initials: KH
authors.lastname: Hung
authors.affiliation: Department of Materials Science and Engineering, BioICT Consortium, National Chiao Tung University, 1001 Ta-Hseuh Road, Hsinchu, Taiwan 300, ROC.
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Wang
authors.affiliation: National Yang-Ming University School of Medicine, No. 155, Sec. 2, Linong Street, Taipei, Taiwan; Department of Ophthalmology, Taipei Veterans General Hospital, No. 201, Shih-Pai Road, Sec. 2, Taipei, Taiwan. Electronic address: jlliu@vghtpe.gov.tw.
authors.forename: Catherine Jui-Ling
authors.initials: CJ
authors.lastname: Liu
authors.affiliation: Department of Materials Science and Engineering, BioICT Consortium, National Chiao Tung University, 1001 Ta-Hseuh Road, Hsinchu, Taiwan 300, ROC. Electronic address: deanmo_liu@yahoo.ca.
authors.forename: Dean-Mo
authors.initials: DM
authors.lastname: Liu
mesh_terms: D000368:Aged; D000818:Animals; D048271:Chitosan; D003102:Colloids; D005782:Gels; D005901:Glaucoma / Q000188:drug therapy*; D006801:Humans; D000077338:Latanoprost; D008297:Male; D011461:Prostaglandins F, Synthetic / Q000008:administration & dosage* / Q000627:therapeutic use; D011817:Rabbits; D012212:Rheology; D013696:Temperature
chemical_list: D003102:Colloids; D005782:Gels; D011461:Prostaglandins F, Synthetic; D000077338:Latanoprost; D048271:Chitosan
keywords: Amphiphilic chitosan; Colloidal gel; Glaucoma; Shear-reversible; Thermogelling