PLGA Nanocapsules Inside of Collagen Nanofibers for Release of Paclitaxel as Agent of Control the Restenosis in Drug Eluting Stents

L. Agudelo, G. Colmenares, R. Pinal, L. Hoyos
Universidad Pontificia Bolivariana,
Colombia

Keywords: electrospinning, bioabsorbible, polymers, nanocapsules, drug delivery, drug-eluting stents, restenosis

Summary:

The most common revascularization procedure for coronary artery disease is the percutaneous coronary intervention (PCI) (Yin et al. 2014; Puranik et al. 2013). However, restenosis after angioplasty and stent implantation has been historically considered the most significant problem in coronary interventions (Yin et al. 2014; Dangas et al. 2010). Drug-eluting stents (DESs) have demonstrated to be effective in decreasing the risk of late restenosis, but the use of currently marketed DESs presents safety concerns, including the non-specificity of therapeutics, incomplete endothelialization that leading to late thrombosis, the need for long-term anti-platelet agents, and local hypersensitivity to polymer delivery matrices (Yin et al. 2014; Puranik et al. 2013). Although DESs can facilitate a drug’s release directly to the restenosis site, a burst of drug release can extremely affect the pharmacological action and is the principal factor that accounts for adverse effects. Therefore, the drug release rate has become an important standard in evaluating DES (Hu et al. 2015). The factors affecting the drug release rate include the drug, drug carrier, coating methods, drug storage, the direction of elution, coating thickness, the pore size in the coating, and release conditions like pH, temperature, release medium and hemodynamics after the stent implantation. This work develops a new delivery system trying to understand better, the factors that influence the drug release. This system uses nanofiber produced by electrospinning technic and bioabsorbable polymeric nanocapsules produced by the nanoprecipitation processes in a recirculated system develop in the research group. We select the electrospinning processes because is perhaps the most promising of all nanotechnologies, in terms of versatility and cost to produce nanofibers, with large surface area, porosity, orientation and dimensions, in a controlled manner with excellent mechanical and easy functionalization properties for multiple applications (Sridhar et al. 2011; Hu et al. 2014; Zeng et al. 2005; Ershuai et al. 2016; Paaver et al. 2015). For this work, we used an electrospinning equipment built at the university, in which you can control the process parameters such as voltage, deposition rate, collector distance, speed and direction of rotation of the collector, to control the morphology and diameter of the nanofibers. The final electrospinning condition to obtain nanofiber of collagen (Sigma-Aldrich) with 99nm and 26nm of standard deviation was 18V, collector distance of 14cm, the flow rate of 0.1mL/h and polymer concentration was 25% W/V in acetic acid and distilled water 1:1. On the other hand, we encapsulated Paclitaxel in bioabsorbable polymeric nanocapsules of PLGA (Resomer 752 H, Evonik) produced in a recirculated system design in the university. The conditions used to encapsulate the paclitaxel was 4mg/mL of polymer concertation, 20% of drug respect to dry polymer, 162mL/min of flow rate in the recirculating system, 0.25% of Tween 80 (Sigma-Aldrich) as surfactant in the aqueous phase and 2:1 ratio between aqueous phase and organic phase. The new delivery system and his individual components were characterized using TEM, SEM, AFM and DLS for the nanocapsules. The control-released curve for paclitaxel was measurement using the HPLC method.