fulltext.study @t Gmail

Long-term and zero-order release of basic fibroblast growth factor from heparin-conjugated poly(l-lactide-co-glycolide) nanospheres and fibrin gel

Paper ID Volume ID Publish Year Pages File Format Full-Text
11572 747 2006 10 PDF Available
Title
Long-term and zero-order release of basic fibroblast growth factor from heparin-conjugated poly(l-lactide-co-glycolide) nanospheres and fibrin gel
Abstract

Controlled long-term delivery of basic fibroblast growth factor (bFGF) could be used as an angiogenesis therapy. In this study, novel heparin-conjugated poly(l-lactide-co-glycolide) (PLGA) nanospheres (HCPNs) were developed for long-term, zero-order delivery of bFGF. HCPNs were prepared by using a coupling reaction between amino-terminated PLGA nanospheres and heparin in the presence of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide. The amount of heparin conjugated to the PLGA nanospheres was increased up to 29-fold by using nanospheres made from lower molecular weight PLGA, or star-shaped PLGA, as compared to nanospheres made from higher molecular weight PLGA, or linear PLGA. The release of bFGF from HCPNs was sustained for 3 weeks with no initial burst release. The bFGF release period was increased to more than 4 weeks using a delivery system of HCPNs suspended in fibrin gel. The release was nearly zero order. The rate of bFGF release from HCPNs in fibrin gel was controlled by the fibrinogen concentration in the fibrin gel. As the fibrinogen concentration increased, the bFGF release rate decreased. The bioactivity of bFGF released from HCPNs in fibrin gel was assessed using human umbilical vein endothelial cell (HUVEC) culture. bFGF released from HCPNs in fibrin gel exhibited HUVEC growth for 15 days, similar to that of cultures to which bFGF in free form was added daily, suggesting that the delivery system of HCPNs in fibrin gel can release bFGF in a bioactive form for a long period. The therapeutic potential of bFGF delivery using HCPNs in fibrin gel was investigated in a mouse limb ischemia model. Immunohistological analysis of mouse ischemic limbs indicated that the microvessel density was much higher in the ischemic limbs treated with bFGF delivery using HCPNs in fibrin gel than in the ischemic limbs treated with daily injections of bFGF or with bFGF delivery using fibrin gel. This study shows that a bFGF delivery system using HCPNs in fibrin gel exhibits controllable, long-term, zero-order release of bFGF and potentiates the angiogenic efficacy of bFGF administration.

Keywords
Basic fibroblast growth factor; Controlled release; Heparin; Poly(l-lactide-co-glycolide) nanosphere; Fibrin gel; Ischemia
First Page Preview
Long-term and zero-order release of basic fibroblast growth factor from heparin-conjugated poly(l-lactide-co-glycolide) nanospheres and fibrin gel
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 27, Issue 8, March 2006, Pages 1598–1607
Authors
, , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us