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.
Department of Drug Formulations, Kaken Pharmaceutical Co. Ltd, Shizuoka, Japan.
K
K
Fukunaga
S
S
Hijikata
K
K
Ishimura
R
R
Sonoda
T
T
Irie
K
K
Uekama
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