Anti-atherosclerotic peptide delivery from a photocrosslinkable biodegradable network.
A water-soluble, 19-mer peptide fragment of serum amyloid A called MFFD is being examined as a possible treatment for atherosclerosis. As a means of administering this drug in a sustained fashion through subcutaneous implantation, a biodegradable network formulation was prepared. The formulation consisted of 1000 and 4000Da alpha,omega-diacrylate oligo(d,l-lactide)-b-poly(ethylene glycol)-b-oligo(d,l-lactide) (DLPEGDLDA) copolymerized with 2700 and 5000Da omega,omega,omega-triacrylate star-poly(epsilon-caprolactone-co-d,l-lactide) using UV irradiation. The influence on the network properties and degradation rate of the network on the amount and type of DLPEGDLDA copolymerized with the two different molecular weight ASCPs were examined in vitro. The networks degraded by bulk hydrolysis at a rate controlled primarily by the molecular weight of the ASCP used. Nevertheless, all the networks were completely degraded within 16 weeks. The MFFD was released in a diffusional manner at a rate influenced by the degree of swelling of the network and the molecular weight of the ASCP used; using an ASCP of a lower molecular weight for a given DLPEGDLDA resulted in a slower release rate. The degree of swelling of the networks was controlled solely by the nature of the PEG used in preparing the DLPEGDLDA, with greater swelling observed with higher PEG molecular weight and for greater amounts of PEG incorporation. The MFFD was not degraded during the photocrosslinking reaction or by potential acidic degradation products that may have accumulated within the device. This formulation provides a means of achieving a desirable release rate from a degradable, water-swellable network through selection of ASCP molecular weight and DLPEGDLDA composition.
Amsden
Brian
B
Department of Chemical Engineering and Human Mobility Research Centre, Queen's University, 19 Division St., Kingston, Ontario, Canada K7L 3N6. brian.amsden@chee.queensu.ca
Qi
Bo
B
D050197:Atherosclerosis / Q000188:drug therapy; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D004058:Diffusion; D004343:Drug Implants; D008970:Molecular Weight; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000737:chemistry; D055668:Photochemical Processes; D011091:Polyesters / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D000685:Serum Amyloid A Protein / Q000008:administration & dosage* / Q000737:chemistry
D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D004343:Drug Implants; D010446:Peptide Fragments; D011091:Polyesters; D011108:Polymers; D000685:Serum Amyloid A Protein; C549494:alpha, omega-diacrylate oligo(lactide)-b-poly(ethylene glycol)-b-oligo(lactide); C549495:omega,omega(I),omega(II)-triacrylate star-poly(caprolactone-co-lactide)