Local Intravascular Drug Delivery: In Vitro Comparison of Three Catheter Systems

Alfke, Heiko; Wagner, Hans‐Joachim; Calmer, Christian; Klose, K. J.

doi:10.1007/s002709900211

Cited by 11 publications

(4 citation statements)

References 18 publications

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“…So far, several preclinical studies reported the use of nanospheres to deliver limus derivatives, but to the best of our knowledge, none of them attempted everolimus delivery in the coronary territory 13,21‐23 . In the study of Granada et al, the authors evaluated feasibility of delivery, long‐term retention and vascular effects of sirolimus nanospheres delivered through a novel porous angioplasty balloon in normal porcine arteries 23 .…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the nanospheres used in our study were designed to minimize their diameter, a key factor in the process of cell internalization 27 . Furthermore, to increase the success rate of short‐term nanospheres delivery, a microporous polytetrafluoroethylene Clearway RX balloon catheter was chosen, which has a proven efficacy of intra‐arterial drug application in previously published experimental studies 11‐13 …”

Section: Discussionmentioning

confidence: 99%

“…The diameter of micropores is 1 μm allowing for easy passage of the experimental nanospheres. Efficacy of intra‐arterial drug delivery was proven in previously published experimental studies 11‐13 …”

Section: Methodsmentioning

confidence: 98%

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Nanospheres encapsulated everolimus delivery into arterial wall–the tissue pharmacokinetics and vascular response experimental study

Milewski

Bryła-Wojciechowska

Buszman

et al. 2020

Cathet Cardio Intervent

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Objective This study aimed to evaluate the pharmacokinetic profile and tissue effects of everolimus delivered into arterial wall using biodegradable nanospheres. Background Delivery of everolimus into the arterial wall is challenging due to its low‐lipophilic profile. Methods A pharmacokinetic study included 28 porcine coronary arterial segments initially injured with balloon angioplasty followed by the local delivery of everolimus encapsulated in nanospheres (EEN) via injection through a microporous delivery catheter. The animals were sacrificed at 1 hour, 1,7,28, and 90‐day follow‐up. In the tissue effects study 16 coronary bare metal stent (BMS) were implanted following EEN delivery, 15 BMS following nanospheres delivery without the drug (reference group) and 16 implanted BMS served as a control. Angiographic and histology follow‐up was scheduled at 28 and 90‐day. Results The study showed high‐everolimus concentrations in arterial tissue early after nanoparticles delivery followed by its gradual decrease to 1.15 ± 0.40 ng/mg at 90 days. Histology analysis showed favorable biocompatibility and healing profile with comparable area stenosis between groups at both time‐points. Conclusions The present study demonstrates for the first time the safety, biocompatibility, and long‐term retention of everolimus in arterial tissue after single local delivery of biodegradable nanospheres.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Nanospheres encapsulated everolimus delivery into arterial wall–the tissue pharmacokinetics and vascular response experimental study

Milewski

Bryła-Wojciechowska

Buszman

et al. 2020

Cathet Cardio Intervent

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“…Local delivery of these agents can be accomplished using specialized catheters that employ passive, pressure-driven, electrically, or mechanically enhanced diffusion for delivery. 25, 26 Using these catheters for direct delivery of the agents only allows for one application or requires an indwelling line that is prone to thrombosis. A single application of reactive PEG that subsequently serves as a specific target for the drug or therapeutic vector to be systemically injected over time may prove to be a more suitable system for long-term delivery.…”

Section: Discussionmentioning

confidence: 99%

In vivo PEG modification of vascular surfaces for targeted delivery

Deglau

Maul

Villanueva

et al. 2012

Journal of Vascular Surgery

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Objective Thrombosis and restenosis remain problematic for many intravascular procedures. Previously, it has been demonstrated that modifying an injured vascular surface with a protein-reactive polymer could block undesirable platelet deposition. As an added benefit, it would be advantageous if one could target therapeutics to the injured site. This study investigates a site-specific delivery system to target microspheres to vascular surfaces modified with a reactive polyethylene glycol tagged with biotin. Methods Rabbit femoral arteries were injured with a 2F embolectomy catheter. Modification of the vascular surface was achieved using a channeled balloon catheter or small diameter tube. Microspheres were injected intravenously through catheterization of the ear vein. Polymer modification on the injured surface and delivery of microspheres was quantified using epi-fluorescence microscopy at 0, 24, 48, and 72 h. Results Polymer modification of the vascular surface could be achieved using a channeled drug delivery catheter or small diameter tube with similar results. Maximum polymer coverage occurred at 0 h and decreased to 85% maximal at 24 h, 72% at 48 h, and 67% at 72 h. The initial number of microspheres per mm2 binding to modified, injured arteries was 304 versus 141 for the unmodified, damaged control (P < .01). At subsequent times, the number of adherent microspheres to modified, injured arteries decreased by 50%, 70%, and 84% at 24, 48, and 72 h, respectively; while non-specific binding to unmodified, injured arteries quickly decreased by 93%. Initial microsphere binding to modified, healthy arteries was 153 microspheres/mm2 as opposed to 26 for the unmodified, healthy controls (P < .01). Conclusions Chemical modification of injured vessels following intravascular procedures can be readily accomplished in vivo to create a substrate for targeted delivery systems. As a proof of concept, targeted microspheres preferentially adhered to polymer-modified surfaces as opposed to injured, unmodified or healthy vascular surfaces.

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Local Gene and Cell Delivery Devices

Sachar

Topol

Contemporary Cardiology

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Local Intravascular Drug Delivery: In Vitro Comparison of Three Catheter Systems

Abstract: Different catheter designs lead to different patterns of local drug delivery. The differences in penetration depth and amount of the substance delivered to the vessel wall should be known and might be useful for targeting specific areas within the vessel wall.

Cited by 11 publications

References 18 publications

Nanospheres encapsulated everolimus delivery into arterial wall–the tissue pharmacokinetics and vascular response experimental study

Nanospheres encapsulated everolimus delivery into arterial wall–the tissue pharmacokinetics and vascular response experimental study

In vivo PEG modification of vascular surfaces for targeted delivery

Local Gene and Cell Delivery Devices

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