Numerous scientists from modern pharmacology and various domains are interested in Controlled drug delivery. Patients’ health is benefited by monitoring the kinetics of drug release which provides an improvement in the effectiveness of the drug-based treatment and reduces the severity of side effects.
The concept of controlled drug delivery systems (CDDS) refers to ensuring “programmed” drug releases over time and delivering the drugs to a specific place in the body. Research in the field of CDDS is being conducted in terms of the mechanisms of releasing the active substances (e.g., by diffusion, ion exchange, or osmosis); release kinetics; materials used as carriers and delivery routes; medicines that can be used for appropriate therapy.
Meeting all of the CDDS objectives (appropriate drug concentration, delivery time, and delivery target place) is a considerable challenge.
Cardiovascular stent design parameters
Stent design parameters may be listed as follows: the dimension of the stent struts, the full expansion of the stent, the radial strength of the stent, the extent of the balloon injury during the stent deployment, the nature of the disease itself (the intensity of the obstruction of the artery), the ability to tolerate the compression exerted by the vessel wall, the minimum longitudinal contraction by the time of expanding, and the amount of flexibility of the stent, especially for curved vessels to suitably flex in them.
Ideal stent material is required to be non-erodible, noncytotoxic, resorbable, flexible, radio-opaque, biocompatible, compatible with the chemical nature of the drug, and ideally, to have sufficient radial strength. Titanium (Ti) and its alloys have been reported as potential materials for the stent backbone, with excellent biocompatibility and corrosion resistance as a result of a stable oxide layer on the surface. The surface coating must be appropriate for the best adhesion of drugs, be compatible with drug molecules, and be biocompatible.
Drug-Eluting Stents (DES)
Contemporary coronary stent technology continues to improve the performance of previous-generation devices by enhancing their design, structure, and component materials. These technologies include new generations of drug-eluting stents, nonpolymeric stents, bioresorbable polymer-coated stents, and fully bioresorbable scaffolds
Prime DESs consisted of three main parts: a permanent metallic platform, a durable polymeric coating, and an active pharmaceutical agent incorporated into the polymeric surface that was being eluted from the polymeric layer. Additionally, the first DES were made not only of steel (iron) but also of nickel, which, according to some authors, could cause recurrent allergic stenosis. Nonetheless, these devices have outperformed BMSs in reducing neointimal proliferation and restenosis based on clinical studies.
Drug releasing kinetics
It is essential to release the correct therapeutic drug dose from a bioresorbable DES for inhibiting smooth muscle cell growth, neointimal hyperplasia, and in-stent restenosis (ISR). Recently, the biodegradable polymeric matrix used as the kingpin of the local drug delivery system is the centre of attention. The work focused on the formulation of the mathematical model elucidating degradation of a drug-loaded polymeric matrix followed by drug release to the adjacent biological tissues.
Polymeric degradation is related to mass-preservation equations. The drug release phenomenon is a model considering the solubilization dynamics of drug particles and diffusion of the solubilized drug through the polymeric matrix, along with the reversible dissociation/recrystallization process. In the tissue phase, reversible dissociation/association, along with the internalization processes of medicine, are taken into account. For this, a two-phase spatiotemporal model was postulated, which ensued a system of partial differential equations. They are solved analytically with an appropriate choice of initial, interface, and boundary conditions. To reflect the potency of the advocated model, the simulated results are analogized with the corresponding experimental data and found laudable agreement to validate the applicability of the model considered. This model seems to foster the delicacy of the mantle enacted by important drug kinetic parameters such as diffusion coefficients, mass transfer coefficients, particle binding, and internalization parameters, which are illustrated through a local sensitivity analysis.
DES Coating techniques
The stent surface plays a critical role in the success of the implantation. It should be biocompatible and show anticoagulation and antithrombotic, anti-inflammatory, and proendothelializing effects after implantation. Thus, surface modifications must meet the following requirements are inhibition of an inflammatory reaction for impeding the thrombosis formation; inhibition of excessive SMCs proliferation and preventing intimial hyperplasia; fast endothelialization from the early time of implantation to promote the creation of an endothelial layer on the stent surface within one month; a quick endothelialization process is essential to decrease the risk of thrombosis to the least amount, and avoiding adverse material-tissue interface interactions; it is necessary for the surface to be biocompatible, especially after complete drug elution.
In the literature, there are two succeeding coating techniques for surface modification: physical and chemical.
The frequently performed stent-coating techniques are dip coating, electrotreated coating, plasma-treated coating, and spray coating.
New Stent systems
Shape-memory stent: It has the ability of self-expansion in the range of body temperature in an ideal situation.
Polymer-Free DES: The inflammatory triggering effects of toxic ions generated from the degradation of polymeric coatings or degradable metal or metal alloys as a surface coating. To avoid effects of polymeric coatings, this is an alternative to preserve the functionality of polymeric DESs, including carrying drug molecules, binding the drug to the stent, and controlling the drug release rate at a suitable rate.
Drug-Eluting Ballons (DEB)
A drug-eluting balloon (DEB) is a non-stent technology in which the vessel wall receives the effective homogenous delivery of antiproliferative drugs from an inflated balloon. It is done to restore the luminal vascularity to treat atherosclerosis, in-stent restenosis, and reduce the risk of late-thrombosis without implanting a permanent object. The balloon technology relies on the concept of targeted drug delivery, which helps in rapid healing of the vessel wall and prevents the proliferation of smooth muscle cells
DEB coating techniques
Innovative coating methods offer a better-controlled mechanism of drug release increasingly, compared to other models of balloons not long ago used for continuous drug release. The solutions proposed are microcapsule coating, hydrogel coating, polymer-free coating, immediate-release coating, bioadhesive coating, and multiple layer coating.
Drug-eluting stents and drug-eluting balloons introduced in recent years for widespread use in CAD treatments inhibit the inflammatory process. They have antimigration and antiproliferative functions, as well as support tissue healing. Despite many clinical studies confirming the angiographic effectiveness of the new types of stents and balloons described here, there are still too-few long-term observations confirming the effectiveness of these treatment methods.
The future of DES is not clear-cut and will depend primarily on technological advances, new structure design solutions, and an improved drug formula. An ideal stent should be characterized by flexibility, strength, and the construction optimally suited to the appropriate drug release. One of the main directions of DES technology development is to modify their surfaces with improved polymer and nanocomposite materials. There is also undergoing work to improve the stent core using biodegradable and bioresorbable materials.