Synthesis Of α-amino Poly (Ethylene Glycol)-poly (lactic Acid) Block Copolymer (α-H₂N-PEG-b-PLA) For Medical Applications

Poly(ethylene glycol)-poly(lactic acid) amphiphilic block copolymers (PEG-b-PLA) can form micelles in water. These micelles have shown considerable potential as MRI diagnose, drug delivery systems and targeted drug delivery, due to their colloidal stability, long circulation after intravenous injection, biocompatibility, and biodegradability. In order to improve cell-specific targeting ability of PEG-b-PLA micellar nanoparticles, a series of H2N-PEG-b-PLA containing functional groups at PEG chain end have been syntheisized. Then H2N-PEG-b-PLAs were used in the field of Gd-DTPA, drug release and targeted drug delivery was researched. The brief contents are shown as follows:1 A series of poly(ethylene glycol)-block-poly(lactic acid) diblock copolymers with functional amino end groups bonding to the PEG block (H2N-PEG-b-PLA) were synthesized through sequential anion ring opening polymerization of EO and LA with potassium bis(trimethylsilyl) amide as initiator. The polymers were characterized by gel permeation chromatography (GPC),'H NMR and FTIR spectroscopy. These investigations indicated that the polymers were obtained with the correct composition, in high purities, and the expected molecular weight.2 A novel biodegradable triblock copolymer poly(L-lysine)-poly(ethylene glycol)-b-poly(L-lactide)-b-(PLL-PEG-PLA) was synthesized by acidolysis of poly(3-benzyloxycarbonyl-L-lysine)-b-poly(ethylene lycol)-b-poly(L-lactide) (PZLL-b-PEG-g-PLA) obtained by the ring-opening polymerization (ROP) of 3-benzyloxycarbonyl-L-lysine N-carboxyanhydride (ZLys NCA) with amino-terminated H2N-PEG-b-PLA, the pendant amino groups of the lysine residues were modified with Diethylenetriaminepentaacetic (DTPA), which was used to chelated paramagnetic Gd3+ Ions. Micelles based on PLL(DTPA)-b-PEG-b-PLA with to the shell layer paramagnetic Gd3+ Ions chelated to the shell layer were prepared. The polymers were characterized by gel permeation chromatography (GPC),1H NMR and FTIR spectroscopy. These investigations indicated that the polymers were obtained with the correct composition, in high purities, and the expected molecular weight. The micelles were determined by fluorescence technique, TEM and DLS. The results indicated that the micelles appear to be spherical in shape and its distribution is quite uniform and the average diameter is 120 nm and possess a low CMC (3.18X10-4 g/L). DTP A Gd chelated to the shell layer of the micelles exhibited spin-latticerelaxivity (r1) five times more than a small-molecular-weight MRI contrast agent (Gd-DTPA).3 H2N-PEG-b-PLA, FITC-PEG-b-PLA and CDBT-loaded micelles were prepared by the interfacial deposition method. The micelles were determined by fluorescence technique, TEM and DLS. The results indicated that the micelles appear to be spherical in shape and its distribution is quite uniform and the average diameter is 120 nm and possess a low CMC (6.31×10-4g/L), which easily helps to form micelles by self-assembly. The micelles exhibited a biphasic drug release with a fast initial burst followed by a sustained release. FITC-labeled micelles can be taken up by cells. The SRB assay showed that empty H2N-PEG-b-PLA micelles were not toxic in the concentration range of 0-400μg/mL while particles with CDBT payload exhibited potent anti-cancer toxicity.4 Folate and AA conjugated functional polymers FOL-PEG-b-PLA and AA-PEG-b-PLA were synthesiszed.1H NMR and FTIR spectroscopy. These investigations indicated that the polymers were obtained with the correct composition. Then Fe3O4 nanoparticles (SPIO) loaded multifunctional micelles were prepared based the mixture of H2N-PEG-b-PLA, FITC-PEG-b-PLA, FOL-PEG-b-PLA and AA-PEG-b-PLA. The micelles were determined by TEM and DLS. The results indicated that the micelles appear to be spherical in shape and its distribution is quite uniform and the average diameter is 90 nm, which easily helps to form micelles by self-assembly. These observations provide direct evidence that SPIO loaded micelles, like SPIO nanoparticles, possess prompt responsiveness to an external magnetic fieled. FITC-labeled micelles can be taken up by cells. These micelles demonstrate the potential to achieve multi tumor targeting of micelles to tumor cells. The multi targeting strategy opens up several opportunities for enhancing drug delivery efficiency and cancer specificity during chemotherapy.