Heparin, controlled release

The controlled release from PTA-SA 50 50 of several drugs known to inhibit the formation of new blood vessels in vivo, cortisone and heparin, is shown in Fig. 9 (15). The inhibitors of angiogenesis delivered in vivo using this polyanhydride were shown to prevent new blood vessel growth for over 3 weeks, following the implantation of the VX2 carcinoma into rabbit cornea (15). 

A Gutowska, YH Bae, SW Kim. Heparin release from thermosensitive hydrogels. J Controlled Release 22 95-99, 1992. 

Substances other than enzymes can be immobilized. Examples include the fixing of heparin on polytetrafluoroethylene with the aid of PEI (424), the controlled release of pesticides which are bound to PEI (425), and the inhibition of herbicide suspensions by addition of PEI (426). The uptake of anionic dyes by fabric or paper is improved if the paper is first catonized with PEI (427). In addition, PEI is able to absorb odorizing substances such as fatty acids and aldehydes. Because of its high molecular weight, PEI can be used in cosmetics and body care products, as well as in industrial elimination of odors, such as the improvement of ambient air quality in sewage treatment plants (428). 

The steady flow rate observed in the heparin infusion study with the corresponding delay in clotting time indicates that the infusion device can provide dependable controlled release. Since the service life, size and flow rate of the device may be varied depending on the requirements of an experiment, these features should make it readily adaptable to the infusion of many other drugs. 

Yang,T., Hussain, A., Bai, S., Khalil, I. A., Harashima, H., and Ahsan, F. (2006), Positively charged polyethylenimines enhance nasal absorption of the negatively charged drug, low molecular weight heparin, J. Controlled Release, 115,289-297. 

Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival- application to proliferation and cyto-toxicity assays. J hnmun Met 65 55-63 Nie T, Baldwin A, Yamaguchi N et al (2007) Production of heparin-functionalized hydrogels for the development of responsive and controlled growth factor delivery systems. J Control Release 122 287-296... 

Figure 9.27 Controlled release activated by cellular infiltration and enzyme activity. Adapted from [93], The gel consists of a fibrin base with covalently bound bidomain peptides. The peptide has a domain that confers heparin binding and a domain that is susceptible to enzymatic degradation. The agent for release is a growth factor that binds with high affinity to heparin. Release is initiated by cellular invasion of the gel and local secretion of an enzyme that cleaves the peptide.

Sakiyama-Elbert, S.E. and J.A. Hubbell, Development of fibrin derivatives for controlled release of heparin-binding growth factors. Journal of Controlled Release, 2000, 65, 389-402. 

In addition to its use as an effective antineoplastic agent, several studies have demonstrated that Taxol is highly effective in preventing restenosis after angioplasty or vascular injury. . The encapsulation of Taxol in polylactic acid microspheres within heparin-chitosan spheres has been shown to provide controlled release of Taxol and... 

Chandy, T., Rao, G.H.R., Wilson, R.F., and Das, G.S., Development of poly (lactic acid)-chitosan comatrix microspheres controlled release of taxol-heparin for preventing restenosis, DrugDeliv. J. Deliv. Targeting Ther. Agents, 8,77, 2001. 

Y. Li, K.G. Neoh, L. Cen, and E.T. Kang, Controlled release of heparin from polypyrrole-poly(vinyl alcohol) assembly by electrical stimulation, J. Biomed. Mater. Res. A, 73A(2), 171-181 (2005). 

M. Fujita, M. Ishihara, M. Simizu, K. Obara, T. Ishizuka, Y. Saito, et al.. Vascularization in vivo caused by the controlled release of fibroblast growth fachx -2 fiom an injectable chitosan/non-anticoagulant heparin hydrt el, Biomaleials 25 (2004) 699-706. 

S.E. Sakiyama-Elbert, J.A. Hubbell, Controlled release of nerve growth factor from a heparin-containing fibrin-based cell ingrowth matrix, J. Control. Release 69 (1) (2000) 149-158. 

A. Zieris, K. Chwalek, S. Prokoph, K.R. Levental, P.B. Welzel, U. Freudenberg, C. Wemer, Dual independent delivery of pro-angiogenic growth factors from starPEG-heparin hydrogels, J. Control. Release 156 (1) (2011) 28-36. 

Karewicz, A., Zasada, K., Szczubialka, K., Zapotoczny, S., Lach, R., Nowakowska, M. Smart alginate-hydroxypropylcellulose microbeads for controlled release of heparin. Int. J. Pharm. 385, 163-169 (2010)... 

Activation-triggered delivery of thrombin inhibitors may offer a solution. As an example a recently developed thrombin-responsive starPEG-heparin hydrogel, already introduced in Section 6.4.2, is a promising biofunctional coating for feedback controlled release of heparin at blood-contacting material surfaces. 

Tefft, S., Bentz, J., Estiidge, T.D. Collagen and heparin matrices for growth factor delivery. Journal of Controlled Release 48, 29-33 (1997)... 

K.N., Leong, K.W., Nurcombe, V., and Cool, S.M. (2006) Controlled release of heparin from poly(e-caprolactone) electrospun fibers. Biomaterials, 27, 2042-2050. 

S.J. (2012) The effect of controlled release of PDGF-BB from heparin-conjugated electrospun PCL/gelatin scaffolds on cellular bioactivity and infiltration. i)/omateriafs, 33, 6709-6720. 

Ishihara M., Obara K., Ishizuka T. et al. 2003. Controlled release of fibroblast growth factors and heparin from photocrosslinked chitosan hydrogels and subsequent effect on in vivo vascularization. J Biomed Mater Res A 6A 551-559. 

Vasudev, S. C., Chandy, T., and Sharma, C. P. 1997. Development of chitosan-polyethylene vinyl acetate comatrix Controlled release of aspirin-heparin for preventing cardiovascular thrombosis. Biomaterials 18 375-381. 

Motlekar, N.A. Youan, B.B. The quest for non-invasive delivery of bioactive macromolecules a focus on heparins. J. Control Release 2006, 113 91-101. 

Moret I, Esteban Peris J, Guillem VM et al (2001) Stability of PEI-DNA and DOTAP-DNA complexes effect of alkaline pH, heparin and serum. J Control Release 76 169-181... 

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