Influence of Drug Incorporation on the Physico-Chemical Properties of Poly(l-Lactide) Implant Coating Matrices-A Systematic Study.

Daniela Arbeiter,Michael Teske,Volkmar Senz,Niels Grabow,Klaus-Peter Schmitz,Stefan Oschatz,Thomas Reske,Dalibor Bajer

doi:10.3390/polym13020292

Daniela Arbeiter, Michael Teske + Show 6 more

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https://doi.org/10.3390/polym13020292

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Abstract

Local drug delivery has become indispensable in biomedical engineering with stents being ideal carrier platforms. While local drug release is superior to systemic administration in many fields, the incorporation of drugs into polymers may influence the physico-chemical properties of said matrix. This is of particular relevance as minimally invasive implantation is frequently accompanied by mechanical stresses on the implant and coating. Thus, drug incorporation into polymers may result in a susceptibility to potentially life-threatening implant failure. We investigated spray-coated poly-l-lactide (PLLA)/drug blends using thermal measurements (DSC) and tensile tests to determine the influence of selected drugs, namely sirolimus, paclitaxel, dexamethasone, and cyclosporine A, on the physico-chemical properties of the polymer. For all drugs and PLLA/drug ratios, an increase in tensile strength was observed. As for sirolimus and dexamethasone, PLLA/drug mixed phase systems were identified by shifted drug melting peaks at 200 °C and 240 °C, respectively, whereas paclitaxel and dexamethasone led to cold crystallization. Cyclosporine A did not affect matrix thermal properties. Altogether, our data provide a contribution towards an understanding of the complex interaction between PLLA and different drugs. Our results hold implications regarding the necessity of target-oriented thermal treatment to ensure the shelf life and performance of stent coatings.

Highlights

The present study addresses the outcome of the incorporation of selected drugs, SIR, PTX, DEX, and it can be estimated, the influence a drug has on the matrix, such dresses the outcome of the incorporation of selected drugs, SIR, PTX, DEX, and cyclosporine A (CYCLO), which are approved or under investigation for the local treatment regarding stent related as a shift in or changes in crystallinity, can differ greatly
Drug-eluting polymer coatings are an indispensable tool in biomedical device engineering, in particular for so-called combination products
Whereas drug release kinetics are clearly important and have been in the focus of extensive research, understanding the interaction of drugs with the drug-carrying polymer matrix is of great interest, especially in the field of drug-eluting stents

Summary

Introduction

Frequently used drugs are from the Limus family, especially sirolimus (SIR) [6,7,8,9], and paclitaxel (PTX) [10], dexamethasone (DEX) [11,12], and cyclosporine A (CYCLO) [13,14]. SIR is mainly used for its immunosuppressant effects to inhibit organ transplant rejection, and shows mammalian target of rapamycin (mTOR) inhibition, reducing cell proliferation and the risk of in-stent restenosis [15,16]. PTX is being applied directly to the target area with drug-eluting balloons or in polymer coatings of DES [3,17], this has recently been questioned [18]. Dexamethasone (DEX), a corticosteroid, is used for its immunosuppressive and anti-inflammatory properties [20]

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