title: Emerging technologies: polymer-free phospholipid encapsulated sirolimus nanocarriers for the controlled release of drug from a stent-plus-balloon or a stand-alone balloon catheter.
abstract: Drug-eluting stents have proven to be effective in reducing the risk of late restenosis. In order to achieve a controlled and prolonged release of the antiproliferative agent, current drug-eluting stents utilise various biodegradable as well as non-erodible polymeric blends to coat the stent surface and to serve as drug carriers. The utilisation of polymeric compounds in current drug-eluting stents may eventually limit their performance as well as their clinical applicability due to the potential induction of undesirable local reactions. The development of alternative, polymer-free drug carriers has the potential to overcome some of the limitations of current drug-eluting stent formulations. Moreover, improvements in drug carriers may also result in an expansion of the technological possibilities for other intravascular drug delivery systems, such as metal-free or even implant-free solutions. This article describes the structure and the preclinical validation profile of a novel phospholipid encapsulated sirolimus nanocarrier, used as a coating in two formulations: a coronary stent-plus-balloon system and a stand-alone balloon catheter. The nanoparticles provided a stable, even and homogenous coating to the devices in both formulations. Dose-finding studies allowed the most appropriate identification of the best nanoparticle structure associated with an extremely efficient transfer of drug to all layers of the vessel wall, achieving high tissue concentrations that persisted days after the application, with low systemic drug leaks.
authors.affiliation: Department of Interventional Cardiology, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Lemos
authors.forename: Vasim
authors.initials: V
authors.lastname: Farooq
authors.forename: Celso K
authors.initials: CK
authors.lastname: Takimura
authors.forename: Paulo S
authors.initials: PS
authors.lastname: Gutierrez
authors.forename: Renu
authors.initials: R
authors.lastname: Virmani
authors.forename: Frank
authors.initials: F
authors.lastname: Kolodgie
authors.forename: Uwe
authors.initials: U
authors.lastname: Christians
authors.forename: Alexander
authors.initials: A
authors.lastname: Kharlamov
authors.forename: Manish
authors.initials: M
authors.lastname: Doshi
authors.forename: Prakash
authors.initials: P
authors.lastname: Sojitra
authors.forename: Heleen M M
authors.initials: HM
authors.lastname: van Beusekom
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Serruys
mesh_terms: D000800:Angioplasty, Balloon / Q000295:instrumentation*; D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D057785:Catheters; D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004337:Drug Carriers; D054855:Drug-Eluting Stents; D005263:Femoral Artery / Q000293:injuries / Q000378:metabolism; D007083:Iliac Artery / Q000293:injuries / Q000378:metabolism; D007700:Kinetics; D008297:Male; D053758:Nanoparticles; D010743:Phospholipids / Q000737:chemistry*; D011817:Rabbits; D020123:Sirolimus / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D013552:Swine; D014018:Tissue Distribution; D057772:Vascular System Injuries / Q000097:blood / Q000473:pathology / Q000628:therapy
chemical_list: D002317:Cardiovascular Agents; D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D010743:Phospholipids; D020123:Sirolimus