title: rhEGF/HP-beta-CD complex in poloxamer gel for ophthalmic delivery.
abstract: The purpose of the present study is to prepare chemically and physically stable rhEGF/poloxamer gel and to investigate its possibility of ophthalmic delivery. The rhEGF/HP-beta-CD complex markedly increased rhEGF stability compared with rhEGF solution at 4 degrees C. The poloxamer gel was composed of poloxamer 407 (16%) and poloxamer 188 (14%). Additive of rhEGF/HP-beta-CD complexes increased the gelation temperature and 0.5% rhEGF/HP-beta-CD complex exhibited a suitable gelation temperature (35.5 degrees C). The gel strength and bioadhesive force decreased by increasing the rhEGF and HP-beta-CD ratio from 1:4 to 1:20 in the complex. The in vitro release of rhEGF from poloxamer gel containing 1:4 rhEGF/HP-beta-CD complex was much slower than that of rhEGF solution and faster than that of 1:20 rhEGF/HP-beta-CD complex. After ocular administration of poloxamer gels in the rabbit, the concentration of rhEGF in tear declined at a first-order elimination. The poloxamer gel containing rhEGF/HP-beta-CD complex increased the area under the concentration-time curve (AUC) of rhEGF in tear fluid compared with gel containing rhEGF solution. 1:20 ratio of rhEGF/HP-beta-CD exhibited high AUC, indicating that rhEGF may be retained in the pre-corneal area for prolonged period. Therefore, the poloxamer gel could be applicable for the development of effective ophthalmic delivery.
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Kim
authors.forename: Zhong Gao
authors.initials: ZG
authors.lastname: Gao
authors.forename: Jeong Sook
authors.initials: JS
authors.lastname: Park
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Kun
authors.initials: K
authors.lastname: Han
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D002626:Chemistry, Pharmaceutical; D003315:Cornea / Q000187:drug effects; D003505:Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000737:chemistry*; D005079:Excipients / Q000008:administration & dosage / Q000737:chemistry; D005782:Gels; D006801:Humans; D008297:Male; D020442:Poloxamer / Q000008:administration & dosage / Q000737:chemistry*; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry*; D047392:beta-Cyclodextrins
chemical_list: D003505:Cyclodextrins; D005079:Excipients; D005782:Gels; D011994:Recombinant Proteins; D047392:beta-Cyclodextrins; D020442:Poloxamer; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D004815:Epidermal Growth Factor