Delivery of paclitaxel from cobalt-chromium alloy surfaces without polymeric carriers

Abstract

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.

Fig. 1

Schematic of preparation of paclitaxel coated cobalt–chromium alloy specimens of Group-A, B, C, and D.

Fig. 2

(a) In vitro drug release profiles of specimens of Groups A and B; (b) Percentage of total drug release profiles of specimens of Groups A and B.

Fig. 3

Amount of drug eluted between every two consecutive time points of Groups A and B (a) and Groups C and D (b).

Fig. 4

(a) In vitro drug release profiles of specimens of Groups C and D; (b) Percentage of total drug release profiles of Group C and D.

Fig. 5

SEM images of control Co–Cr alloy (a); group-C (spherical crystals) (b); group-C (needle crystals) (c); group-A (d); group-D (spherical crystals) (e); group-B (f).

Fig. 6

AFM images of control Co–Cr (a,b), Group-C (c,d), Group-A (e,f), Group-D (g,h), and Group-B (i,j).

Fig. 7

XPS determined atomic compositions of control, Groups C and A specimens (a), and control, Groups D and B specimens (b).

Fig. 8

XPS determined C/Co+Cr +W +Ni, O/Co + Cr +W+Ni, and C/O ratios of control, Groups C and A (a), and Groups D and B (b).

Fig. 9

XPS C 1s spectra of control Co–Cr and groups-A to D (a); C 1s spectrum of paclitaxel (powder form) (b); O 1s spectra of control Co–Cr alloy and groups-A to D (c); and O 1s spectra of paclitaxel (powder form) (d).

Fig. 10

(a) Schematic of the formation of PAT coating on Co–Cr alloy, (b) Schematic of the drug release from Groups C and D–Initial burst release of PAT crystals followed by a slow and sustained release of PAT molecules, (c) Schematic of the drug release from Groups A and B–Slow and sustained release of PAT molecules.