Studies On Preparation And Properties Of Biodegradable TAT-PEG-PLA

Biocompatible drug carriers have attracted a great deal of attentions of researchersrecently. The cell membrane permeability is very important to the carriers. A type of blockcopolymer micelles made by PEG-PLA with cell membrane permeability has beeninvestigated in this thesis and doxorubicin was used as a model drug to study the cellmembrane permeability of the micelle. Heherobifunctional PEG with a maleimide group onone end and a hydroxyl group at the other was prepared with two different methods in thiswork. Functional diblock copolymer Mal-PEG-PLA was prepared by the ring-openingpolymerization of LA in the presence of the initiator Mal-PEG-OH and the catalyst stannousoctoate (Sn(Oct)2). The physico-chemical properties of the block polymers includingcomposition, molecular weight were confirmed by1H-NMR, MS and GPC. TheMal-PEG-PLA micelles were prepared using a solvent displacement method andcharacterized by dynamic light scattering (DLS) for size and size distribution andtransmission electron microcopy (TEM) for morphologies.Cell penetrating peptides TAT and FITC-TAT were synthesized by the solid phasepeptide synthesis method. The structure of the peptides was certified by MS andMALDI-TOF-MS. Doxorubicin-loaded micelles (Mal-PEG-PLA/DOX) were prepared byself-assembly of the amphiphilic block copolymers in aqueous solution, and TAT (FITC-TAT)was conjugated to drug-loaded micelles (Mal-PEG-PLA/DOX) via the reaction between thethiol in the peptide and maleimide groups on the surface of the micelles. Drug-loading dosageand encapsulation efficiency were evaluated by UV and the size, size distribution andmorphology of the micelles were characterized by DLS and TEM, respectively. The antitumoractivity of the drug-loading nanoparticles against human cervical cancer HeLa cell wasevaluated by MTS method.