TY - JOUR
T1 - Tailored drug release from biodegradable stent coatings based on hybrid polyurethanes
AU - Guo, Qiongyu
AU - Knight, Pamela T.
AU - Mather, Patrick T.
N1 - Funding Information:
The authors are grateful for the financial support of this work by Boston Scientific Corporation. We would like to thank Prof. Mark D. Pagel at Case Western Reserve University for generously providing the usage of the HPLC.
PY - 2009/8/4
Y1 - 2009/8/4
N2 - Highly adjustable and precisely controllable drug release from a biodegradable stent coating was achieved using a unique family of nanostructured hybrid polyurethanes. These polyurethanes are polyhedral oligosilsesquioxane thermoplastic polyurethanes (POSS TPUs) featuring alternating multiblock structures formed by nanostructured hard segments of POSS and biodegradable soft segments of a polylactide/caprolactone copolymer (P(DLLA-co-CL)) incorporating polyethylene glycol (PEG) covalently. POSS aggregated to form crystals serving as physical crosslinks on the nanometer scale, while the soft segments were designed carefully to modulate the drug release rate from the POSS TPU stent coatings in PBS buffer solution, with 90% of the drug releasing from within half a day to about 90 days. In order to interpret the underlying drug release mechanisms, an approximation model capable of describing the entire drug release process was developed. This model is based on Fickian diffusional transport, but also takes into account the polymer degradation and/or swelling of the coating, depending on the dominance of the degradation/swelling behavior compared to that of the diffusion characteristics. A general methodology was utilized for statistically fitting the drug release curves from the POSS TPU stent coatings using the model. We observed that the fitted initial drug release diffusion coefficient covered more than three orders of magnitude, depending on the polymer glass transition temperature (Tg), according to a modified Williams-Landel-Ferry (WLF) equation. In addition, two additional rate constants describing the impact of degradation and swelling on drug elution were determined and found to be consistent with independent measurements. Our results clearly show that the studied hybrid polyurethane family allows a drug release rate that is effectively manipulated through variation in polymer Tg, degradation rate, and thickness increment rate.
AB - Highly adjustable and precisely controllable drug release from a biodegradable stent coating was achieved using a unique family of nanostructured hybrid polyurethanes. These polyurethanes are polyhedral oligosilsesquioxane thermoplastic polyurethanes (POSS TPUs) featuring alternating multiblock structures formed by nanostructured hard segments of POSS and biodegradable soft segments of a polylactide/caprolactone copolymer (P(DLLA-co-CL)) incorporating polyethylene glycol (PEG) covalently. POSS aggregated to form crystals serving as physical crosslinks on the nanometer scale, while the soft segments were designed carefully to modulate the drug release rate from the POSS TPU stent coatings in PBS buffer solution, with 90% of the drug releasing from within half a day to about 90 days. In order to interpret the underlying drug release mechanisms, an approximation model capable of describing the entire drug release process was developed. This model is based on Fickian diffusional transport, but also takes into account the polymer degradation and/or swelling of the coating, depending on the dominance of the degradation/swelling behavior compared to that of the diffusion characteristics. A general methodology was utilized for statistically fitting the drug release curves from the POSS TPU stent coatings using the model. We observed that the fitted initial drug release diffusion coefficient covered more than three orders of magnitude, depending on the polymer glass transition temperature (Tg), according to a modified Williams-Landel-Ferry (WLF) equation. In addition, two additional rate constants describing the impact of degradation and swelling on drug elution were determined and found to be consistent with independent measurements. Our results clearly show that the studied hybrid polyurethane family allows a drug release rate that is effectively manipulated through variation in polymer Tg, degradation rate, and thickness increment rate.
KW - Biodegradable polymer
KW - Drug delivery
KW - Drug-eluting stents
KW - POSS
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U2 - 10.1016/j.jconrel.2009.04.016
DO - 10.1016/j.jconrel.2009.04.016
M3 - Article
C2 - 19376173
AN - SCOPUS:67649119649
SN - 0168-3659
VL - 137
SP - 224
EP - 233
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 3
ER -