Polymeric micelles as drug delivery systems: a reactive polymeric micelle carrying aldehyde groups

Abstract

Nanospheric particles as drug delivery systems are gaining increasing interest in the biomedical field. Nanospheres have been proven as efficient drug delivery systems for intravenous administration because of their comparatively long bloodstream circulation. A novel approach in the field of polymeric drug delivery systems was introduced by the formation of polymeric micelles and subsequently by functionalized polymeric micelles. Functionalized polymeric micelles are expected to find a wide application in the fields of drug delivery and diagnosis since the possibility of coupling to bioactive substances is provided. A large number of densely packed functional groups on the outer shell of the micelle allows an immobilization of biologically active substances at a high density. This is a great advantage for utilizing this particular type of nanosphere in the biomedical field. The possibilities of synthesizing heterobifunctional block copolymers will be demonstrated and the influence of the individual block length on the micelle properties will be discussed. Functionalized polymeric micelles were synthesized from poly(ethylene glycol) (PEG) and poly(lactide) (PLA), and combine the advantages given by the hydrophobic PLA core and the hydrophilic PEG corona. An established quantitative synthetic method for the formation of heterobifunctional PEG was advanced and applied to the block copolymerization. A heterobifunctional block copolymer was synthesized, terminated by an acetal group at the PEG end and a vinyl group was introduced at the PLA end in a one-pot synthesis. After the micellization the acetal groups on the micelle surface were converted into aldehyde groups by an acidic treatment. Aldehyde groups can react rapidly with primary amines forming Schiff bases, a potential future pathway for the conjugation of functionalized polymeric micelles with proteins. PLA was chosen as core-forming segment since it is a biodegradable, non-toxic polymer that is well established as implant material. Dynamic and static light scattering was applied to determine the micelle size and shape and to study the dependence of the micelle geometry on the block length of the copolymer. © 1998 John Wiley & Sons, Ltd.