rhEGF/HP-beta-CD complex in poloxamer gel for ophthalmic delivery.
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.
Kim
Eun Young
EY
College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea.
Gao
Zhong Gao
ZG
Park
Jeong Sook
JS
Li
Hong
H
Han
Kun
K
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
D003505:Cyclodextrins; D005079:Excipients; D005782:Gels; D011994:Recombinant Proteins; D047392:beta-Cyclodextrins; D020442:Poloxamer; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D004815:Epidermal Growth Factor