A new bioerodible system for sustained local drug delivery based on hydrolytically activated in situ macromolecular association.
To prolong the duration of polymer erosion over existing approaches for sustained local drug delivery, we investigated a new bioerodible system based on hydrolytically activated in situ formation of interpolymer complexes in binary blends of high MW poly(vinyl methyl ether-co-maleic anhydride) (PVMMA) and poly(ethylene oxide) (PEO). In an aqueous environment of use, the hydrophobic PVMMA component of the blend undergoes hydrolysis converting the anhydride to free carboxylic acid groups which in turn form in situ intermolecular complexes with the PEO component of the blend. The formation of such hydrogen-bonded complexes with a condensed structure at the blend surface helps to retard the further progression of polymer erosion and drug release. The effects of PVMMA/PEO composition on blend morphology, polymer erosion and drug release were evaluated with the aid of fluorescence labeled PVMMA. The results show a decrease in miscibility in PVMMA/PEO blend with increasing PEO content. At low PEO contents (below 40%), the in vitro rate of release of a model drug metronidazole decreases with increasing PEO content, resulting in extended release duration over several days. On the other hand, excessive phase separation at PEO contents above 40% gives rise to higher rate and shorter duration of drug release.
Li
Yan
Y
Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario M5S 3M2, Canada.
Lee
Ping I
PI
D020341:Absorbable Implants; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D046911:Macromolecular Substances / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry*; D011759:Pyrrolidines / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry*; D014753:Vinyl Compounds / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry*
D003692:Delayed-Action Preparations; D046911:Macromolecular Substances; D011759:Pyrrolidines; D014753:Vinyl Compounds; C475304:poly(vinylpyrrolidone-co-dimethyl maleic anhydride)