Aluminium beta-cyclodextrin sulphate as a stabilizer and sustained-release carrier for basic fibroblast growth factor.
The water-insoluble aluminium salt of beta-cyclodextrin sulphate (Al.beta-CyD-Sul) was used as a stabilizer and sustained-release carrier for recombinant human basic fibroblast growth factor (bFGF). An adsorbate of bFGF with Al.beta-CyD-Sul was prepared by incubating the protein with a suspension of Al.beta-CyD-Sul in water. The mitogenic activity of bFGF released from the adsorbate, as indicated by the proliferation of kidney cells of baby hamster (BHK-21), was almost comparable with that of the intact bFGF. Al.beta-CyD-Sul significantly protected bFGF from proteolytic degradation by pepsin and alpha-chymotrypsin, compared with the water-soluble sodium salt. The in-vitro release of bFGF from the adsorbate was sustained in proportion to a rise in the ratio of Al.beta-CyD-Sul to the protein in the adsorbate. Of the bFGF preparations evaluated, the adsorbate of bFGF with Al.beta-CyD-Sul, when given subcutaneously to the rat, showed the most prominent increase in the formation of granulation tissues, due to the stabilization and slow-release of the mitogen. The limited data presented here suggest that the adsorbate of bFGF with Al.beta-CyD-Sul has a potent therapeutic efficacy for wound healing, and may be applicable to oral protein formulations for the treatment of intestinal mucosal erosions.
Fukunaga
K
K
Department of Drug Formulations, Kaken Pharmaceutical Co. Ltd, Shizuoka, Japan.
Hijikata
S
S
Ishimura
K
K
Sonoda
R
R
Irie
T
T
Uekama
K
K
D000818:Animals; D002460:Cell Line; D002918:Chymotrypsin; D006224:Cricetinae; D003505:Cyclodextrins / Q000737:chemistry*; D003692:Delayed-Action Preparations; D005079:Excipients; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008934:Mitogens; D010434:Pepsin A; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D014945:Wound Healing / Q000187:drug effects; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D003692:Delayed-Action Preparations; D005079:Excipients; D008934:Mitogens; D011994:Recombinant Proteins; D047392:beta-Cyclodextrins; D016222:Fibroblast Growth Factor 2; D002918:Chymotrypsin; D010434:Pepsin A; C031215:betadex