Biological evaluation and drug delivery application of cationically modified phospholipid polymers.
Phospholipid-like polymers based on 2-methacryloyloxyethyl phosphorylcholine containing varying amounts of the cationically charged monomer choline methacrylate (CMA) from 0 to 30 wt% have been prepared. Substrates coated with these materials were shown to bind significantly lower amounts of specific proteins compared to the uncoated control. ELISA assays demonstrated that fibrinogen did not bind appreciably to coatings containing 0-30% CMA, whereas albumin binding was seen to increase significantly as the CMA content of the coating increased. Platelet activation assays, measurement of plasma coagulation time and whole blood contact scanning electron micrography demonstrated that the haemocompatibility of the coatings was shown to be unaffected by the CMA component. The CMA polymer coatings have been shown to absorb/adsorb many different drug compounds covering a wide range of molecular weights and release these in a controlled fashion. The range of cationic polymers assessed can interact with the net negative charge found in many large therapeutic biomolecules, such as DNA fragments used in gene therapy, that may be of interest in the preventative treatment of conditions such as restenosis. Coronary stents coated with 6% or 20% CMA-containing polymers have been shown to load and release this type of genetic material irrespective of molecular weight of the biomolecule. Ex vivo and in vivo studies have shown that these compounds can be delivered to the stented section of the vessel with very low quantities delivered outside the vessel target area.
Palmer
Rosemary R
RR
Biocompatibles UK Ltd., Drug Delivery, Chapman House, Farnham Business Park, Weydon Lane, Farnham, Surrey GU9 8QL, UK.
Lewis
Andrew L
AL
Kirkwood
Laura C
LC
Rose
Susanna F
SF
Lloyd
Andrew W
AW
Vick
Terry A
TA
Stratford
Peter W
PW
D000042:Absorption; D000327:Adsorption; D000818:Animals; D001158:Arteries / Q000473:pathology / Q000601:surgery; D001780:Blood Coagulation Tests; D002412:Cations; D002478:Cells, Cultured; D002794:Choline / Q000031:analogs & derivatives* / Q000737:chemistry*; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D003331:Coronary Vessels / Q000473:pathology* / Q000601:surgery; D016503:Drug Delivery Systems / Q000379:methods*; D005340:Fibrinogen / Q000737:chemistry*; D006801:Humans; D008422:Materials Testing; D008689:Methacrylates / Q000737:chemistry*; D009841:Oligonucleotides / Q000008:administration & dosage / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D015539:Platelet Activation / Q000502:physiology*; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry*; D013552:Swine
D002412:Cations; D020099:Coated Materials, Biocompatible; D008689:Methacrylates; D009841:Oligonucleotides; D010743:Phospholipids; D012709:Serum Albumin; C491922:choline methacrylate; D005340:Fibrinogen; D002794:Choline