Shell cross-linked nanoparticles containing hydrolytically degradable, crystalline core domains

Shell cross-linked knedel-like nanoparticles (SCKs) possessing an amphiphil ic core-shell morphology consisting of a cross-linked shell and a hydrolyti cally degradable, crystalline core domain were synthesized from poly(epsilo n-caprolactone)-b-poly(acrylic acid) (PCL-b-PAA) amphiphilic diblock copoly mers via a two-step process: self-assembly of PCL-b-PAA into polymer micell es followed by cross-linking of the hydrophilic shell layer via condensatio n reactions between the carboxylic acid functionalities of PAA and the mine groups of 2,2'-(ethylenedioxy)bis(ethylamine). PCL-b-PAA was prepared from the selective hydrolysis of a poly(epsilon-caprolactone)-b-poly(tert-butyl acrylate) (PCL-b-PtBA) precursor, which was synthesized by ring opening po lymerization (ROP) of epsilon-caprolactone (epsilon-CL) followed by atom tr ansfer radical polymerization (ATRP) of tert-butyl acrylate (tBA). Selectiv e hydrolysis of the tert-butyl ester groups of the PtBA block by reaction w ith trimethylsilyl iodide (TMSI), followed by reaction with aqueous acid, g ave PCL-b-PAA with nearly 100% conversion and minimal cleavage of the PCL c hain segments. Alternatively, selective thermal deprotection of the tert-bu tyl esters was also performed. SCKs prepared from PCL-b-PAA formed globular nanoparticles when deposited from aqueous solution onto a mica surface at room temperature. The effects of copolymer composition and cross-linking ex tent on the properties of the SCKs were investigated by tapping-mode atomic force microscopy (AFM). The PCL core domains exhibited interesting crystal lization and melting behaviors, in which the PCL melting transition tempera ture increased as the SCK core volume increased. This suggests that the lam ellar thicknesses of PCL cores in larger SCKs are greater. The selective hy drolysis of the polyester (PCL) core domain in the presence of amide cross- links throughout the shell layer to yield nanocage structures was studied b y H-1 NMR and AFM. The degradation of PCL was monitored by H-1 NMR, from th e appearance of the resonance for sodium 6-hydroxyhexanoate under basic hyd rolysis conditions. From AFM analysis for the nanoparticles adsorbed onto a mica surface,it was found that, under both acidic and basic hydrolysis con ditions, the core-degraded nanocages formed broader structures with decreas ed height, in comparison with SCKs before core hydrolysis.