Effects of permeation enhancers BL-9 and Brij-78 on absorption of four peptide eyedrops in rabbits

Systemic absorption of 4 peptide drugs through ocular route was enhanced by permeation enhancers, BL-9 and Brij-78. Gonadorelin (LHRH) was the smallest molecule (M(r) = 1200) and its systemic delivery was most efficiently enhanced by BL-9 (17.0-20.8 times) and Brij-78 (13.9-21.5 times). Although bombesin (M(r) = 1620), atrial natriuretic peptides (ANP) (M(r) = 3240), and adrenocorticotropic hormone (ACTH) (M(r) = 4540) had molecular weight ranged widely, their systemic absorption through ocular route was enhanced by BL-9 (6.1-8.3 times) and Brij-78 (6.5-9.0 times) in about the same degree. BL-9 enhanced systemic absorption of peptide drugs faster and reached peak peptide concentrations in 5-20 min. On the other hand, Brij-78 took 20-60 min to reach to peak concentration of peptide drugs in the blood. These results indicate that systemic delivery of peptide drug through ocular route is a feasible one particularly when the absorption enhancers are used.