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To study the molecular origins of hemocompatibility, the blood plasma protein human serum albumin (HSA) was covalently grafted to a nanosized probe tip at the end of a soft, microfabricated cantilever force transducer. The net force versus separation distance between the HSA-modified probe tip and three different model surfaces, including (1) gold; (2) a hydrophobic, CH3-terminated alkanethiol self-assembling monolayer (SAM); and (3) a hydrophilic, COO --terminated alkanethiol SAM in aqueous sodium phosphate buffer solution (PBS, ionic strength (IS) ) 0.01 M, pH ) 7.4), was recorded and compared to the values of various theoretical models. The approach interaction of the HSA probe tip on the COO --terminated SAM and Au substrates was found to be purely repulsive for D < 15 nm, nonlinear with decreasing separation distance, and consistent with electrostatic double layer repulsion. The approach interaction of the HSA probe tip on the CH3-terminated SAM substrate was found to be purely attractive, long range (D < 80 nm), nonlinear with decreasing separation distance, and much greater in magnitude and range than that known for van der Waals interactions between hydrocarbon SAMs terminated with hydrophilic chemical groups on Au. Large adhesive energies were observed for the HSA probe tip on both the CH3-terminated SAM and Au surfaces (e-29 mN/m, -22 to -73kBT/protein), while smaller adhesive energies were observed on the COO --terminated SAM surface (e -4.9 mN/m, -5.3 to -12kBT/protein). It was shown that short-range adhesive contacts between the HSA chain segments and these surfaces give rise to energy dissipating mechanisms, such as HSA entropic molecular elasticity and enthalpic unfolding forces (deformation and rupture of noncovalent intramolecular bonds) and noncovalent bond rupture of the HSA chain segments adsorbed to the surface. IntroductionThe interaction between the surface of an implanted artificial medical device and blood typically results in nonspecific, noncovalent surface adsorption of blood plasma proteins followed by platelet adhesion and activation, initiation of the coagulation cascade, and thrombus formation. 1,2 In the absence of transport limitations, the interaction potential between the protein and the surface as a function of separation distance, U(D), will determine whether a protein will adsorb and at what rate. U(D) is typically a superposition of numerous nonspecific repulsive (e.g. electrostatic counterion double layer, steric, hydration, etc.) and attractive (e.g. van der Waals, hydrophobic, H-bonding, ionic, etc.) components that can lead to complicated functional forms that vary with the strength and range of the constituent interactions. 3,4 Generally, improved protein resistance can be achieved by maximizing repulsive interactions and minimizing attractive ones. Subsequent stages of protein adsorption become increasingly complex and depend on the conformation, orientation, and mobility of the adsorbed proteins, the time-scale of conformational changes, protein exchange and desorp...

Polymer-based carriers are commonly used to deliver drugs from stents. However, adverse responses to polymer coatings have raised serious concerns. This research is focused on delivering drugs from stents without using polymers or any carriers. Paclitaxel (PAT), an anti-restenotic drug, has strong adhesion towards a variety of material surfaces. In this study, we have utilized such natural adhesion property of PAT to attach these molecules directly to cobalt–chromium (Co–Cr) alloy, an ultra-thin stent strut material. Four different groups of drug coated specimens were prepared by directly adding PAT to Co–Cr alloy surfaces: Group-A (PAT coated, unheated, and ethanol cleaned); Group-B (PAT coated, heat treated, and ethanol cleaned); Group-C (PAT coated, unheated, and not ethanol cleaned); and Group-D (PAT coated, heat treated and not ethanol cleaned). In vitro drug release of these specimens was investigated using high performance liquid chromatography. Groups A and B showed sustained PAT release for up to 56 days. A simple ethanol cleaning procedure after PAT deposition can remove the loosely bound drug crystals from the alloy surfaces and thereby allowing the remaining strongly bound drug molecules to be released at a sustained rate. The heat treatment after PAT coating further improved the stability of PAT on Co–Cr alloy and allowed the drug to be delivered at a much slower rate, especially during the initial 7 days. The specimens which were not cleaned in ethanol, Groups C and D, showed burst release. PAT coated Co–Cr alloy specimens were thoroughly characterized using scanning electron microscopy, atomic force microscopy, and X-ray photoelectron spectroscopy. These techniques were collectively useful in studying the morphology, distribution, and attachment of PAT molecules on Co–Cr alloy surfaces. Thus, this study suggests the potential for delivering paclitaxel from Co–Cr alloy surfaces without using any carriers.

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