“…The addition of PEG observed an increased in peptide release for both films and stents that was expected . We believe that the release from the PEG formulations followed the “colocalization model,” where peptide colocalized with hydrophilic excipients release along with the efflux of the excipients. The subsequent release of the peptide is dependent on the leaching rates of the excipients and the rate of diffusion of peptide out of the films and stents.…”
Despite the success that drug eluting stents (DES) have achieved for minimizing in-stent restenosis (ISR), the anti-restenotic agents used in DES have been implicated in delayed endothelial healing and impairment of endothelial functions. Cenderitide (CD-NP) is a novel anti-proliferation chimeric peptide of semi-endothelial 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 (ECs). The micro-bicinchoninic acid (BCA) protein assay was used to investigate the CD-NP release from films and stents. Cenderitide-contained films blended with poly(ethylene glycol) and its copolymer exhibited higher release kinetics compared to neat PCL formulation. Cenderitide-eluting stents (CES) was produced by coating bare metallic stents with CD-NP entrapped poly(ε-caprolactone) using an ultrasonic spray coater. The investigation of CD-NP on in vitro cells revealed that CD-NP inhibits HCaSMCs proliferation but exhibits no effects on 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 HCaSMCs proliferation but did not hamper HUVECs proliferation in vitro, suggesting that it has potential to reduce ISR without retarding the endothelialisation healing in vivo.
“…The addition of PEG observed an increased in peptide release for both films and stents that was expected . We believe that the release from the PEG formulations followed the “colocalization model,” where peptide colocalized with hydrophilic excipients release along with the efflux of the excipients. The subsequent release of the peptide is dependent on the leaching rates of the excipients and the rate of diffusion of peptide out of the films and stents.…”
Despite the success that drug eluting stents (DES) have achieved for minimizing in-stent restenosis (ISR), the anti-restenotic agents used in DES have been implicated in delayed endothelial healing and impairment of endothelial functions. Cenderitide (CD-NP) is a novel anti-proliferation chimeric peptide of semi-endothelial 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 (ECs). The micro-bicinchoninic acid (BCA) protein assay was used to investigate the CD-NP release from films and stents. Cenderitide-contained films blended with poly(ethylene glycol) and its copolymer exhibited higher release kinetics compared to neat PCL formulation. Cenderitide-eluting stents (CES) was produced by coating bare metallic stents with CD-NP entrapped poly(ε-caprolactone) using an ultrasonic spray coater. The investigation of CD-NP on in vitro cells revealed that CD-NP inhibits HCaSMCs proliferation but exhibits no effects on 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 HCaSMCs proliferation but did not hamper HUVECs proliferation in vitro, suggesting that it has potential to reduce ISR without retarding the endothelialisation healing in vivo.
Timolol maleate (TM) has been used for many years for the reduction of intraocular pressure (IOP) in glaucoma patients. However, the topical mode of administration (eyedrops) is far from optimal because of the issues of low bioavailability, high drug wastage, and lack of patient compliance. Suboptimal control of the IOP leads to disease progression and eventually to blindness. Ideally, TM is delivered to the patient so that its action is both localized and sustained for 3 months or more. In this work, we developed a subconjunctival TM microfilm for sustained, long-term delivery of TM to the eyes, using the biodegradable elastomer poly(lactide-co-caprolactone) (PLC). The copolymer is biocompatible and has flexibility and mechanical characteristics suitable for a patient-acceptable implant. Controlling the release of TM for 3 months is challenging, and this work describes how, by using a combination of multilayering and blending with poly(ethylene glycol) (PEG) copolymers, we were able to develop a TM-incorporated biodegradable film that can deliver TM at a therapeutic dose for 90 days in vitro. The data was further confirmed in a diseased primate model, with sustained IOP-lowering effects for 5 months with a single implant, with acceptable biocompatibility and partial degradation.
“…Cenderitide is a peptide that has similar molecular length and characteristics as HHC36. Studies by both Ng et al , and Huang et al have shown that the addition of PEG copolymers increases both the cumulative release and the sustained controlled-release rates of cenderitide. These studies showed similar peptide elution trends as this study.…”
Section: Resultsmentioning
confidence: 99%
“…Various strategies have been explored to hasten the release of the active compound from PCL. , One common strategy involves the addition of hydrophilic components like poly(ethylene glycol) (PEG) into the polymer formulation. − A study by Zhang et al found that addition of the hydrophilic PEG component changes the morphology of the originally dense network of PCL and increases the porosity of the polymer, hence altering the resulting drug release rate . In addition, the overall drug release was found to increase proportionally with increasing amounts of PEG, suggesting that drug delivery rates could be controlled by varying the proportion of PCL to PEG.…”
Catheter-associated urinary tract
infections (CAUTIs) are common
and pose significant costs to healthcare systems. To date, this problem
is largely unsolved as commercially available antimicrobial catheters are still lacking in functionality
and performance. A prior study by Lim et al. (Biotechnol. Bioeng.201811520002012) reported the development
of a novel anhydrous polycaprolactone (PCL) polymer formulation with
controlled-release functionality for antimicrobial peptides. In this
follow-up study, we developed an improved antimicrobial peptide (AMP)–impregnated
poly(ethylene glycol) (PEG)–polycaprolactone (PCL) anhydrous
polymer coating for enhanced sustained controlled-release functionality
to provide catheters with effective antimicrobial properties. Varying
the ratio of PEG and PEG–PCL copolymers resulted in polymers
with different morphologies, consequently affecting the AMP release
profiles. The optimal coating, formulated with 10% (w/w) PEG–PCL
in PCL, achieved a controlled AMP release rate of 31.65 ± 6.85
μg/mL daily for up to 19 days, with a moderate initial burst
release. Such profile is desired for antimicrobial coating as the
initial burst release acts as a sterilizer to kill the bacteria present
in the urinary tract upon insertion, and the subsequent linear release
functions as a prophylaxis to deter opportunistic microbial infections.
As a proof-of-concept application, our optimized coating was then
applied to a commercial silicone catheter for further antibacterial
tests. Preliminary results revealed that our coated catheters outperformed
commercial silver-based antimicrobial catheters in terms of antimicrobial
performance and sustainability, lasting for 4 days. Application of
the controlled-release coating also aids in retarding biofilm formation,
showing a lower extent of biofilm formation at the end of seven inoculation
cycles.
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