Immobilization of heparin: approaches and applications

Abstract

Heparin, an anticoagulant, has been used in many forms to treat various diseases. These forms include soluble heparin and heparin immobilized to supporting matrices by physical adsorption, by covalent chemical methods and by photochemical attachment. These immobilization methods often require the use of spacers or linkers. This review examines and compares various techniques that have been used for the immobilization of heparin as well as applications of these immobilized heparins. In the applications reviewed, immobilized heparin is compared with soluble heparin for efficient and versatile use in each of the various applications.

Fig. (1)

Structure of glycosaminoglycans (X = H or SO₃⁻; Y = Ac or SO₃⁻).

Fig. (2)

Schemes for the immobilization of heparin onto the EVAL polymer using (a) APC and (b) HMDI as linkers.

Fig. (3)

Protocols for making biocompatible vinyl surfaces with longer spacers such as TEPA and pHEMA.

Fig. (4)

Immobilization of heparin ionically through DED (DEDQ = quarternized DED).

Fig. (5)

A comparison of the bioefficiency of covalently (dotted line) and ionically formed surfaces (solid line).

Fig. (6)

Formation of PU-AB by oxygen plasma glow discharge and graft polymerization.

Fig. (7)

Functional group introduction and heparin immobilization on PU-AB.

Fig. (8)

Scheme showing the reaction protocol for the preparation of heparinized PU surfaces.

Fig. (9)

The effect of CNBr conc. on the amount of heparin immobilized (heparin concentration = 2 mg/ml, 25 °C, pH 7.4) (solid circle: p(HEMA), solid square: p(HEMA-AA), empty circle: p(HEMA-DMAEMA), empty square: p(HEMA-MMA).

Fig. (10)

CT, APTT, PT data of various microsphere surfaces (grey: without heparin immobilized, black: with heparin immobilized; diagonal: APTT, solid: PT, checker board: CT).

Fig. (11)

Immobilization of heparin and HA onto poly(ethylene) through O₂/H₂O RFGD plasma treatment (steps A,B,C) or PE-CVD AA RFGD poly(ethylene) (steps 1,2,3).

Fig. (12)

Thrombin time measurements of various surface modified PE substrates.

Fig. (13)

Schematic representation of the preparation of heparinized p(DAPAAm)-b-(PDMAAm)-block-graft-copolymer (a) Dithiocarbamate-derivatized PST film; (b) p(DMAPAAm) graft polymer; (c) heparin; and (d) p(DMAAm) graft polymer.

Fig. (14)

Schematic representation of PTFE surfaces.

Fig. (15)

Overall process of the immobilization of insulin and /or heparin on PET.

Fig. (16)

The amount of thrombus formed on PETs with various surface modifications after 30 min incubation (The value corresponding to glass was taken as 100%).

Fig. (17)

Plasma recalcification time as a function of surface-modified PETs.

Fig. (18)

APTT as a function of surface modifications.

Fig. (19)

Amount of platelets adhered on surface modified PETs with the initial platelet concentration as 100. (Circle - 60 min; diamond - 30 min incubation time).

Fig. (20)

Serotonin released from platelets on PETs with various surface modifications (solid square: 30 min without imipramine; solid circle: 30 min with imipramine; empty square: 60 min without imipramine; solid circle: 60 min with imipramine).

Fig. (21)

Heparinized PHEMA hydrogel.

Fig. (22)

Schematic representation of the various approaches of heparin immobilization on biological surfaces (a) tissue without heparinization (b) tissue with ionically bound heparin (c) tissue with covalently bound heparin via multi point attachment (d) tissue with covalently bound heparin via end point attachment.

Fig. (23)

Scheme for the heparinization of PAN through two approaches.

Fig. (24)

Heparinization of PPY through PEGMA and CC.

Fig. (25)

Heparinization of polysulfone with/without chitosan linkers.

Fig. (26)

Covalent immobilization of heparin on PLGA surface by EDC/NHS coupling.

Fig. (27)

Covalent attachment of chitosan/heparin complex to polyacrylonitrile membrane

Fig. (28)

Plasma Protein Adsorption on the surface modified PAN membranes (square: HPF; circle: HSA).

Fig. (29)

Activated partial thromboplastin time values of celluloseheparin composite in comparison with some other heparinized polymeric surfaces.

Fig. (30)

Schematic representation of the activation of heparin towards free amino groups.

Fig. (31)

APTT measurements of modified CNTs (crossed bar: No CNTs; empty bar: Pristine CNTs; black bar: PEI-CNTs; grey bar: Hep-PEI-CNTs).