rhEGF/HP-β-CD complex in poloxamer gel for ophthalmic delivery

• Published in: International journal of pharmaceutics 2002-02, Vol.233 (1), p.159-167
• Main Authors: Kim, Eun-Young, Gao, Zhong-Gao, Park, Jeong-Sook, Li, Hong, Han, Kun
• Format: Article
• Language: English
• Subjects: 2-Hydroxypropyl-beta-cyclodextrin; Animals; beta-Cyclodextrins; Biological and medical sciences; Chemistry, Pharmaceutical; Complexation; Cornea - drug effects; Cyclodextrins - administration & dosage; Cyclodextrins - chemistry; Drug Delivery Systems - methods; Epidermal Growth Factor - administration & dosage; Epidermal Growth Factor - chemistry; Excipients - administration & dosage; Excipients - chemistry; Gels; General pharmacology; Humans; Hydroxypropyl-β-cyclodextrin; Male; Medical sciences; Ophthalmic delivery; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Poloxamer; Poloxamer - administration & dosage; Poloxamer - chemistry; Rabbits; Recombinant Proteins - administration & dosage; Recombinant Proteins - chemistry; rhEGF
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(01)00933-4

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-β-CD complex markedly increased rhEGF stability compared with rhEGF solution at 4 °C. The poloxamer gel was composed of poloxamer 407 (16%) and poloxamer 188 (14%). Additive of rhEGF/HP-β-CD complexes increased the gelation temperature and 0.5% rhEGF/HP-β-CD complex exhibited a suitable gelation temperature (35.5 °C). The gel strength and bioadhesive force decreased by increasing the rhEGF and HP-β-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-β-CD complex was much slower than that of rhEGF solution and faster than that of 1:20 rhEGF/HP-β-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-β-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-β-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.