Hyaluronan microspheres for sustained gene delivery and site-specific targeting.
Hyaluronan is a naturally occurring polymer that has enjoyed wide successes in biomedical and cosmetic applications as coatings, matrices, and hydrogels. For controlled delivery applications, formulating native hyaluronan into microspheres could be advantageous but has been difficult to process unless organic solvents are used or hyaluronan has been modified by etherification. Therefore, we present a novel method of preparing hyaluronan microspheres using adipic dihydrazide mediated crosslinking chemistry. To evaluate their potential for medical applications, hyaluronan microspheres are incorporated with DNA for gene delivery or conjugated with an antigen for cell-specific targeting. The results show that our method, originally developed for preparing hyaluronan hydrogels, generates robust microspheres with a size distribution of 5-20mum. The release of the encapsulated plasmid DNA can be sustained for months and is capable of transfection in vitro and in vivo. Hyaluronan microspheres, conjugated with monoclonal antibodies to E- and P-selectin, demonstrate selective binding to cells expressing these receptors. In conclusion, we have developed a novel microsphere preparation using native hyaluronan that delivers DNA at a controlled rate and adaptable for site-specific targeting.
Department of Biomedical Engineering, State University of New York, 348 Psychology A Building, Stony Brook, NY 11794-2580, USA.
Yang H
YH
Yun
Douglas J
DJ
Goetz
Paige
P
Yellen
Weiliam
W
Chen
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D002448:Cell Adhesion; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D042783:Endothelial Cells / Q000378:metabolism; D018390:Gene Targeting / Q000379:methods*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000493:pharmacokinetics; D046911:Macromolecular Substances; D008422:Materials Testing; D008863:Microspheres; D008968:Molecular Conformation; D010316:Particle Size; D010957:Plasmids / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats / Q000235:genetics; D013499:Surface Properties; D014162:Transfection / Q000379:methods*; D014471:Umbilical Veins / Q000378:metabolism
D000936:Antigen-Antibody Complex; D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D046911:Macromolecular Substances; D006820:Hyaluronic Acid