A Novel Reactive Polymeric Micelle with Aldehyde Groups on Its Surface

Abstract

It is reported that amphiphilic AB block copolymers form in selective solvents micellar structures.' These nanospheric particles combine the advantages given by the hydrophobic core, which can act as a vehicle for medical drugs, and the unique properties of a hydrophilic ~ h e 1 1 . ~ ~ PEO chains attached to a surface or forming the corona of a nanospheric particle in an aqueous medium exhibit rapid chain motions and have a large excluded volume. The steric repulsion resulting from a loss of configurational entropy of the bound PEO upon the approach of a foreign particle and the low interfacial free energy contribute to the extraordinary properties of PEO-covered surface^.^-'^ The small size, apparent thermodynamic stability, and exceptional biological features of polymeric micelles favor their application in the biomedical field.11-14 Recently, a facile and quantitative synthetic method for the formation of heterobifunctional poly(ethy1ene oxide) was reported.15J6 If one of the functional end groups in the heterobifunctional PEO can selectively initiate the polymerization of a hydrophobic monomer, a new heterobifunctional AB block copolymer can be created, retaining the other functional group (acetal group) a t the PEO chain end. As a core-forming segment, polylactide (PLA) was chosen for the following reasons: (1) The ring-opening reaction of a lactide can be initiated by the living chain end of potassium ethylene oxide without any side reaction. (ii) PLAS are biodegradable and nontoxic polymers, which are widely utilized as implant materials. This is an important prerequisite considering a future application of this system in the biomedical field. (iii) Nanoparticles, consisting of block copolymers of a-methoxypoly(ethy1ene oxide) and PLA are suited for drug de1i~ery.l~ Furthermore, the micelle formation and transformation of acetal into aldehyde groups on the micelle surface were discussed. An aldehyde group reacts rapidly with primary amino groups, forming a Schiff base, a chemical path which could be employed in the hture for conjugations with proteins. Experimental Section. Materials and Methods. Commercial tetrahydrofuran (THF), 3,3-diethoxypropanol, ethylene oxide (EO), and lactide were purified conventionally.l8 Potassium naphthalene was used as a THF solution.1g GPC measurements were carried out using a Shimadzu 6A liquid chromatograph equipped with a PEO-calibrated TSK gel column (G4000HXL, G3000HXL, G2500HXL) and an internal RI detector (RID-6A). THF containing 2% of triethylamine was used as eluent a t a flow rate of 1 mumin. 'H-NMR