title: Fabrication of a composite system combining solid lipid nanoparticles and thermosensitive hydrogel for challenging ophthalmic drug delivery.
abstract: The purpose of this study was to explore a composite thermosensitive in situ gelling formulation using the distribution of solid lipid nanoparticles (SLNs) among poloxamer-based hydrogels as a potential carrier for novel ocular drug delivery. SLNs containing the model drug Resina Draconis were prepared using a melt-emulsion ultrasonication method. A central composite design (CCD) was adopted to screen the thermosensitive hydrogel (THG) formulation. After aqueous SLNs were dispersed into the THG matrices, the physicochemical properties of the SLNs were characterized before and after their incorporation into hydrogels. The in vitro corneal penetration experiment, ocular irritant test and transcorneal mechanism across the cornea have been previously described to predict the feasibility for the proposed ophthalmic application. Finally, the optimal THGs consisted of 27.8% (w/v) poloxamer 407 and 3.55% (w/v) poloxamer 188. The particle size of the SLNs remained within the colloidal range. In vitro corneal penetration studies revealed a nearly steady sustained drug release. The hen's egg test-chorioallantoic membrane (HET-CAM) test indicated that all of the tested polymer systems were non-irritant. Coumarin-6 labeled SLNs formulated into THGs displayed a more homogeneous fluorescence with a deeper penetration intensity into the cornea at various times. Taken together, these results suggest that the SLN-based THG system can be used as a potential vehicle for ocular application.
authors.affiliation: College of Pharmacy, Taishan Medical University, Taian 271016, PR China. Electronic address: haojifu@163.com.
authors.forename: Jifu
authors.initials: J
authors.lastname: Hao
authors.affiliation: College of Pharmacy, Taishan Medical University, Taian 271016, PR China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Taishan Medical University, Taian 271016, PR China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Bi
authors.affiliation: College of Pharmacy, Taishan Medical University, Taian 271016, PR China.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Teng
authors.affiliation: College of Pharmacy, Taishan Medical University, Taian 271016, PR China.
authors.forename: Jianzhu
authors.initials: J
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Taishan Medical University, Taian 271016, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: College of Pharmacy, Taishan Medical University, Taian 271016, PR China.
authors.forename: Qiankui
authors.initials: Q
authors.lastname: Li
authors.affiliation: College of Pharmacy, Taishan Medical University, Taian 271016, PR China.
authors.forename: Jimei
authors.initials: J
authors.lastname: Zhang
authors.affiliation: College of Pharmacy, Taishan Medical University, Taian 271016, PR China.
authors.forename: Fengguang
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China. Electronic address: liujiyong999@126.com.
authors.forename: Jiyong
authors.initials: J
authors.lastname: Liu
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D002152:Calorimetry, Differential Scanning; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000378:metabolism; D003315:Cornea / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D066298:In Vitro Techniques; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D010539:Permeability; D011817:Rabbits; D012984:Software; D013223:Statistics as Topic; D013499:Surface Properties; D013696:Temperature
chemical_list: D008055:Lipids; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate
keywords: Central composite design; Ocular drug delivery; Resina Draconis; Solid lipid nanoparticle; Thermosensitive hydrogels