Cenderitide-eluting film for potential cardiac patch applications.

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

The effect of polyethylene glycol structure on paclitaxel drug release and mechanical properties of PLGA thin films

Thin films of poly(lactic acid-co-glycolic acid) (PLGA) incorporating paclitaxel typically have slow release rates of paclitaxel of the order of 1 μg day−1 cm−2. For implementation as medical devices a range of zero order release rates (i.e. 1–15 μg day−1 cm−2) is desirable for different tissues and pathologies. Eight and 35 kDa molecular weight polyethylene glycol (PEG) was incorporated at 15%, 25% and 50% weight ratios into PLGA containing 10 wt.% paclitaxel. The mechanical properties were assessed for potential use as medical implants and the rates of release of paclitaxel were quantified as per cent release and the more clinically useful rate of release in μg day−1 cm−2. Paclitaxel quantitation was correlated with the release of PEG from PLGA, to further understand its role in paclitaxel/PLGA release modulation. PEG release was found to correlate with paclitaxel release and the level of crystallinity of the PEG in the PLGA film, as measured by Raman spectrometry. This supports the concept of using a phase separating, partitioning compound to increase the release rates of hydrophobic drugs such as paclitaxel from PLGA films, where paclitaxel is normally homogeneously distributed/dissolved. Two formulations are promising for medical device thin films, when optimized for tensile strength, elongation, and drug release. For slow rates of paclitaxel release an average of 3.8 μg day−1 cm−2 using 15% 35k PEG for >30 days was achieved, while a high rate of drug release of 12 μg day−1 cm−2 was maintained using 25% 8 kDa PEG for up to 12 days.NRF (Natl Research Foundation, S’pore)Accepted versio

Surface morphology of films loaded with CD-NP.

<p>SEM micrograph on day 0 of CD-NP loaded (a) film 1, (b) film 2 and (c) film 3 and after day 30 release in (d) film 1, (e) film 2 and (f) film 3.</p

Cyclic 3′5′ guanosine monophosphate (cGMP) generation in human cardiac fibroblast (HCF).

<p>cGMP generation in HCF induced by (a) different CD-NP concentration and (b) 24 hour peptide released from film 1, 2 and 3, *p<0.05 versus control.</p

Summary of formulation information.

<p>Formulation manufacturing condition and initial release classification.</p

A novel bioabsorbable drug-eluting tracheal stent

Currently available silicone and metallic stents for tracheal stenosis are associated with problems of granulations, mucus trapping, and difficult removals. Our aim was to develop a novel bioabsorbable tracheal stent with mitomycin C (MMC) drug elution to circumvent such problems

Effects of CD-NP on human cardiac fibroblast (HCF).

<p>Relative anti-proliferation actions of (a) CD-NP of different concentration and (b) CD-NP released from film 1, 2 and 3 (1 day, 2 days, 3 days and 5 days) in HCF via colormetric bromodeoxyuridine (BrdU), *p<0.05.</p

Correlation between relative cell index (RCI) and CD-NP concentration.

<p>Correlation between RCI (primary y-axis) and peptide concentration (secondary y-axis) of (a) Daily infusion of CD-NP, (b) film 1, (c) film 2 and (d) film 3 over 5 days (x-axis).</p

Accumulated release profiles of CD-NP loaded films for 30 days.

<p>(a) Accumulated peptide release profiles of film 1, 2 and 3 and (b) bottom left graph shows the release concentrations of film 1, 2 and 3 over 30 days; top right graph is a zoomed in on the bottom left graph.</p