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Despite the success that drug-eluting stents ( DESs) have achieved for minimizing in-stent restenosis ( ISR), the antirestenotic agents used in DES have been implicated in delayed endothelial healing and impairment of endothelial functions. Cenderitide ( CD- NP) is a novel antiproliferation chimeric peptide of semiendothelial origin; thus, this paper aims to demonstrate the selectivity aspect of this new peptide via in vitro evaluation on key players in ISR-smooth muscle cells ( SMCs) and endothelial cells. The microbicinchoninic acid protein assay was used to investigate the CD- NP release from films and stents. Cenderitide-containing films blended with poly(ethylene glycol) and its copolymer exhibited higher release kinetics compared with neat poly(ε-caprolactone) ( PCL) formulation. Cenderitide-eluting stents ( CES) was produced by coating bare metallic stents with CD- NP entrapped PCL using an ultrasonic spray coater. The investigation of CD- NP on in vitro cells revealed that CD- NP inhibits human coronary smooth muscle cells ( HCa SMCs) proliferation but exhibits no effects on human umbilical vein endothelial cells ( HUVECs) proliferation. Moreover, CD- NP released up to 7 days displayed inhibitory effects on SMCs proliferation. The CES produced in this work shows that the released CD- NP inhibits HCa SMCs proliferation but did not hamper HUVECs proliferation in vitro, suggesting that it has potential to reduce ISR without retarding the endothelialization healing in vivo. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3631-3640, 2014 [ABSTRACT FROM AUTHOR]

In this work, we focused on the development and investigation of controlled release matrices for a novel cardiotherapeutic peptide, cenderitide ( CD- NP) that has shown to be useful for control of ventricular remodeling. To circumvent the hydrophilicity disparity between CD- NP and hydrophobic polymer matrix, a cosolvent system (water/dichloromethane) was selected for investigation. The effect of emulsification conditions, addition of poly(ethylene glycol) ( PEG) and its copolymer on the release mechanism and profile were investigated. To verify the retention of bioactivity of entrapped CD- NP in different formulations, the generation of 3′,5′ cyclic guanosine monophospate (c GMP) and the inhibition of human cardiac fibroblast ( HCF) were evaluated. The results showed that neat poly(ε-caprolactone) matrices carried out via two distinct emulsification conditions had either an unacceptably high burst or incomplete release of CD- NP; and the addition of PEG and its copolymer obtained intermediate profiles. Our confocal laser scanning microscopy and surface morphological investigations showed that the copolymer excipient was superior in playing stabilizer role by colocalizing and redistributing peptide throughout the matrix, making the release less sensitive to emulsification conditions. Furthermore, the released CD- NP is able to generate the cGMP and inhibit the HCF proliferation. Our investigations showed that CD- NP-loaded platforms can be a feasible option to provide sustained antifibrotic moderation of fibrotic scar formation and be potentially used to alleviate the adverse effects of cardiac remodeling. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:1400-1410, 2014 [ABSTRACT FROM AUTHOR]

Cenderitide, also known as CD-NP, is a designer peptide developed by combining native mammalian c-type natriuretic peptide (CNP) and the C-terminus isolated from the dendroapis natriuretic peptide (DNP) of the venom from the green mamba. In early studies, intravenous and subcutaneous infusion of cenderitide was reported to reduce left ventricular (LV) mass and ameliorate cardiac remodelling. In this work, biodegradable polymeric films encapsulating CD-NP were developed and were investigated for their in vitro release and degradation characteristics. Subsequently, the bioactivity of released peptide and its effects on human cardiac fibroblast (HCF) were explored. We achieved sustained release from three films with low, intermediate and high release profiles for 30 days. Moreover, the bioactivity of released peptide was verified from the elevated production of cyclic guanosine monophospate (cGMP). The CD-NP released from films was able to inhibit the proliferation of hypertrophic HCF as well as suppress DNA synthesis in HCF. Furthermore, the sustained delivery from films showed comparable or superior suppressive actions on hypertrophic HCF compared to daily infusion of CD-NP. The results suggest that these films could be used to inhibit fibrosis and reduce cardiac remodelling via local delivery as cardiac patches. [ABSTRACT FROM AUTHOR]

A bilayer swellable drug-eluting ureteric stent (BSDEUS) is engineered and implemented, as a sustained drug delivery platform technology that enhances localized drug delivery to the highly impermeable urothelium, for the treatment of urothelial diseases such as strictures and carcinomas. On deployment, the device swells to co-apt with the ureteric wall and ensure drug availability to these tissues. BSDEUS consists of a stent spray-coated with a polymeric drug containing polylactic acid-co-caprolactone (PLC) layer which is overlaid by a swellable polyethylene glycol diacrylate (PEGDA) based hydrogel. In-vitro quantification of released drug demonstrated a tunable time-profile, indicating sustained delivery over 1-month. The PEGDA hydrogel overlayer enhanced drug release and transport into explanted porcine ureteric tissues ex-vivo , under a simulated dynamic fluid flow. A preliminary pilot in-vivo feasibility study, in a porcine model, demonstrated that the swollen hydrogel co-apts with the urothelium and thus enables localized drug delivery to the target tissue section. Kidney functions remained unaffected and device did not result in either hydronephrosis or systemic toxicity. This successful engineering of a bilayer coated stent prototype, demonstrates its feasibility, thus offering a unique solution for drug-based urological therapy. [ABSTRACT FROM AUTHOR]

Bioresorbable scaffolds (BRS) represent a novel horizon in interventional cardiology for the treatment of coronary artery disease. The technology was introduced to overcome limitations of current metallic drug-eluting stents such as late in-stent restenosis and permanently caging the vessel. The concept of the BRS is to provide temporal support to the vessel during healing before being degraded and resorbed by the body, promoting restoration of the vessel vasomotion. Currently, there are several BRS that are under development or already commercially available. Although several reviews have elegantly covered progress of current clinical programs and newer scaffold technologies, little is available currently to describe the mechanistic differences between biomaterials used in current and newer bioresorbable technologies. This aim of this review is to discuss the status of the different BRS technologies and materials currently under investigation, explore the newer strategies being adopted to improve material mechanical properties and optimize BRS degradation and summarize the performance of BRS in the clinical setting so far. [ABSTRACT FROM AUTHOR]

Modern implantable medical devices have evolved beyond serving as physical surrogates, to also playing an active role in restoring bodily functions. The progress of implantable medical devices is the culmination of advances in various scientific fields such as material science, microelectronics and biomaterials. The use of polymers in biomedical applications is highly attractive, especially in soft tissue applications as polymers have the potential to elicit appropriate host tissue response. However, homopolymers often do not encompass all the desired characteristics such as mechanical properties, degradability, biocompatibility or bio-functionality. The concepts of polymer blending or polymer composites were introduced to overcome the inadequacies when using a single polymer in cardiovascular applications. Through polymer blending, polymer scaffolds made up of two or more polymers can yield scaffold stiffness closer to the human myocardium and improved hydrophilicity for better cell interaction and improved biodegradability. Polymer composites, which utilizes to reinforce the base polymer, have demonstrated improved the compliance of the vascular graft similar to human native vessels. This review presents an overview of fabrication techniques and novel applications of polymer blends and polymer composites in cardiovascular implants, ranging from coronary stents to tissue engineered constructs. [ABSTRACT FROM AUTHOR]

Advances in material science and innovative medical technologies have allowed the development of less invasive interventional procedures for deploying implant devices, including scaffolds for cardiac tissue engineering. Biodegradable materials (e.g., resorbable polymers) are employed in devices that are only needed for a transient period. In the case of coronary stents, the device is only required for 6–8 months before positive remodelling takes place. Hence, biodegradable polymeric stents have been considered to promote this positive remodelling and eliminate the issue of permanent caging of the vessel. In tissue engineering, the role of the scaffold is to support favourable cell-scaffold interaction to stimulate formation of functional tissue. The ideal outcome is for the cells to produce their own extracellular matrix over time and eventually replace the implanted scaffold or tissue engineered construct. Synthetic biodegradable polymers are the favoured candidates as scaffolds, because their degradation rates can be manipulated over a broad time scale, and they may be functionalised easily. This review presents an overview of coronary heart disease, the limitations of current interventions and how biomaterials can be used to potentially circumvent these shortcomings in bioresorbable stents, vascular grafts and cardiac patches. The material specifications, type of polymers used, current progress and future challenges for each application will be discussed in this manuscript. [ABSTRACT FROM AUTHOR]