Locally delivered nanoencapsulated tyrphostin (AGL-2043) reduces neointima formation in balloon-injured rat carotid and stented porcine coronary arteries.

Heiden Department of Cardiology, Bikur Cholim Hospital, Jerusalem, Israel.
Biomaterials (Impact Factor: 8.31). 03/2005; 26(4):451-61. DOI: 10.1016/j.biomaterials.2004.02.040
Source: PubMed

ABSTRACT Local delivery of antiproliferative drugs encapsulated in biodegradable nanoparticles (NP) has shown promise as an experimental strategy for preventing restenosis development. A novel PDGFRbeta-specific tyrphostin, AGL-2043, was formulated in polylactide-based nanoparticles and was administered intraluminally to the wall of balloon-injured rat carotid and stented pig coronary arteries. The disposition and elimination kinetics within the vessel wall, as well as the antirestenotic potential of the novel drug and delivery system, were evaluated. The efficacy and the local drug elimination kinetics were affected by the size of the NP and the drug-carrier binding mode. Despite similar arterial drug levels 90 min after delivery in rats, small NP were more efficacious in comparison to large NP (90 and 160 nm, respectively). AGL-2043 selectively inhibited vascular SMC in a dose-dependent manner. The antiproliferative effect of nanoencapsulated tyrphostin was considerably higher than that of surface-adsorbed drug. In the pig model, intramural delivery of AGL-2043 resulted in reduced in-stent neointima formation in the coronary arteries over control despite similar degrees of wall injury. The results of this study suggest that locally delivered tyrphostin AGL-2043 formulated in biodegradable NP may be applicable for antirestenotic therapy independent of stent design or type of injury.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The medical device industry is growing at a very fast pace and has recorded great research activity over the past decade. The interdisciplinary nature of this field has made it possible for researchers to incorporate principles from various allied areas like pharmaceutics, bioengineering biotechnology, chemistry, electronics, biophysics etc. to develop superior medical solutions, offering better prospects to the patient. Moreover, micro and nanotechnology has made it possible to positively affect at the sub-micron scales, the cellular processes initiated upon implantation. Literature is rife with findings on various implants and this review comprehensively summarizes the recent advances in micro/nano scale implantable medical devices - particularly cardiovascular implants, neural implants, orthopedic and dental implants and other miscellaneous implants. Over the years, medical implants have metamorphosed from mere support providing devices to smart interventions participating positively in the healing process. We have highlighted the current research in each area emphasizing on the value addition provided by micro/nano scale features, its course through the past and the future perspectives focusing on the unmet needs.
    Journal of controlled release : official journal of the Controlled Release Society. 06/2014;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Percutaneous coronary intervention (PCI) has become the most common revascularization procedure for coronary artery disease. The use of stents has reduced the rate of restenosis by preventing elastic recoil and negative remodeling. However, in-stent restenosis remains one of the major drawbacks of this procedure. Drug-eluting stents (DESs) have proven to be effective in reducing the risk of late restenosis, but the use of currently marketed DESs presents safety concerns, including the non-specificity of therapeutics, incomplete endothelialization leading to late thrombosis, the need for long-term anti-platelet agents, and local hypersensitivity to polymer delivery matrices. In addition, the current DESs lack the capacity for adjustment of the drug dose and release kinetics appropriate to the disease status of the treated vessel. The development of efficacious therapeutic strategies to prevent and inhibit restenosis after PCI is critical for the treatment of coronary artery disease. The administration of drugs using biodegradable polymer nanoparticles as carriers has generated immense interest due to their excellent biocompatibility and ability to facilitate prolonged drug release. Despite the potential benefits of nanoparticles as smart drug delivery and diagnostic systems, much research is still required to evaluate potential toxicity issues related to the chemical properties of nanoparticle materials, as well as to their size and shape. This review describes the molecular mechanism of coronary restenosis, the use of DESs, and progress in nanoparticle drug- or gene-eluting stents for the prevention and treatment of coronary restenosis.
    Theranostics 01/2014; 4(2):175-200. · 7.81 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Percutaneous coronary intervention (PCI) is one of the most commonly performed invasive medical procedures in medicine today. Since the first coronary balloon angioplasty in 1977, interventional cardiology has seen a wide array of developments in PCI. Bare metal stents (BMS) were soon superseded by the revolutionary drug-eluting stents (DES), which aimed to address the issue of restenosis found with BMS. However, evidence began to mount against DES, with late-stent thrombosis (ST) rates being higher than that of BMS. The bioabsorbable stent may be a promising alternative, providing vessel patency and support for the necessary time required and thereafter degrade into safe non-toxic compounds which are reabsorbed by the body. This temporary presence provides no triggers for ST, which is brought about by non-endothelialized stent struts and drug polymers remaining in vivo for extended periods of time. Likewise, nano-theranostics incorporated into a bioabsorbable stent of the future may provide an incredibly valuable single platform offering both therapeutic and diagnostic capabilities. Such a stent may allow delivery of therapeutic particles to specific sites thus keeping potential toxicity to a minimum, improved ease of tracking delivery in vivo by embedding imaging agents, controlled rate of therapy release and protection of the implanted therapy. Indeed, nanocarriers may allow an increased therapeutic index as well as offer novel post-stent implantation imaging and diagnostic methods for atherosclerosis, restenosis and thrombosis. It is envisioned that a nano-theranostic stent may well form the cornerstone of future stent designs in clinical practice.
    Theranostics 01/2014; 4(5):514-533. · 7.81 Impact Factor