title: Investigation of cenderitide controlled release platforms for potential local treatment of cardiovascular pathology.
abstract: 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 (cGMP) 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.
authors.affiliation: School of Materials Science & Engineering, Nanyang Technological University, Singapore, 639798, Singapore.
authors.forename: Xu Wen
authors.initials: XW
authors.lastname: Ng
authors.forename: Yingying
authors.initials: Y
authors.lastname: Huang
authors.forename: Kerh Lin
authors.initials: KL
authors.lastname: Liu
authors.forename: Freddy Y C
authors.initials: FY
authors.lastname: Boey
authors.forename: Subbu S
authors.initials: SS
authors.lastname: Venkatraman
mesh_terms: D002318:Cardiovascular Diseases / Q000188:drug therapy*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical / Q000379:methods; D006152:Cyclic GMP / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000494:pharmacology*; D004655:Emulsions / Q000737:chemistry; D005079:Excipients / Q000737:chemistry; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008752:Methylene Chloride / Q000737:chemistry; D045265:Natriuretic Peptides / Q000737:chemistry* / Q000494:pharmacology*; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology; D012910:Snake Venoms / Q000737:chemistry* / Q000494:pharmacology*; D020257:Ventricular Remodeling / Q000187:drug effects; D014867:Water / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D004655:Emulsions; D005079:Excipients; D045265:Natriuretic Peptides; D011091:Polyesters; D011108:Polymers; D012910:Snake Venoms; D014867:Water; C016240:polycaprolactone; D011092:Polyethylene Glycols; D008752:Methylene Chloride; C575835:cenderitide; D006152:Cyclic GMP
keywords: CD-NP; biodegradable polymers; biomaterials; controlled release; excipients; formulation; natriuretic peptide; peptide delivery