Cenderitide-Eluting Film for Potential Cardiac Patch Applications

Abstract

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.

Natriuretic peptides and cardio-renal disease

“…CD-NP in vitro activated cGMP and suppressed cell proliferation of human cardiac fibroblasts induced by cardiotrophin-1 (a marker of HF and myocardial infarction) [104]. Recent research has proposed that CD-NP-eluting polymeric films may eventually be employed as cardiac patches which, via local application, could be used to suppress cardiac remodeling and fibrosis [108]. The first clinical trial in healthy human volunteers reported that CD-NP was well tolerated and activated cGMP, induced natriuresis, and suppressed aldosterone without causing excessive hypotension [109].…”

In Vitro Evaluation of Cenderitide‐Eluting Stent I —An Antirestenosis and Proendothelization Approach

“…Currently, CD‐NP is undergoing initial evaluation in humans by Mayo Clinic to address ventricular remodeling. Our previous work have also demonstrated that controlled release of CD‐NP from films and patches sustained the suppression of human cardiac fibroblast proliferation for cardiac remodeling indication . However, its utility as an antirestenotic compound have not yet been tested.…”

Natriuretic peptide based therapeutics for heart failure: Cenderitide: A novel first-in-class designer natriuretic peptide

“…In experimental models of cardiovascular disease, novel nanoparticle gel polymer strategies are being tested [44]. Further, a novel film delivery system in which Cenderitide is released from a patch-like device around the heart is also being tested [45]. An oral delivery platform is favored but remains a challenge to achieve acceptable levels of bioavailability.…”