Synthesis Of Beta-cyclodextrin-conjugated Biodegradable Amphiphilic Polyester And Their Controlled Release Of Protein And Anticancer Drugs

The main advantage of the reversed micelles is the selective solubilisation of biomolecules inside reversed micelles which provides an aqueous environment protecting the bioactivities of the biomolecules,such as proteins, peptide. Therefore, the study on drug carriers using the reverse micelle system exhibited great significance.A series of poly(ethylene glycol)-poly(lactide-co-glycolide)(PEG-PLGA) copolymers were synthesized by a ring-opening polymerization of D,L-lactide and glycolide mixed in different proportions,using MPEG or 4-arm PEG as initiators and stannous octoate as catalyst. The terminal hydroxyl group of PEG-PLGA was carboxylated using succinic anhydride, and then a series of β-cyclodextrin-conjugated poly(ethylene glycol)-poly(lactide-co-glycolide)(PEG-PLGA) copolymers were synthesized by reacting with mono(6-ethylenediamine-6-deoxy)-β-cyclodextrin(CDen) and ethylenediamino bridged bis-β-cyclodextrin(BCDen), respectively, under a dehydration condensation of 4-dimethylamino-pyridine(DMAP) and dicyclohexylcarbodiimide(DCC). The chemical structures of copolymers were confirmed by 1H NMR and FT-IR spectroscopy. β-CD possess low toxicity, certain hydrophilicity and the cavity size, which can interact with bovine serum albumin(BSA) by binding the aromatic groups and alkyl chains of BSA. Additionally, β-CD could not form supramolecular network with PEG-PLGA. Therefore, β-CD-conjugated PEG-PLGA could be fabricated as reverse micelles, which could accommodate BSA in organic solvent with improved encapsulation efficiency(EE) and loading capacity(LC). Moreover, we demonstrated a one-step approach to construct macroporous protein-containing films using these reverse micelles. The films with ordered pore arrays were directly prepared from reverse micelles. Interestingly, the protein was totally located in the wall of the pores.Polyurethane was then used to encapsulate doxorubicin-loaded nanoparticles by emulsification method, and In vitro cytocompatibility and antitumor activity, as well as cellular uptake experiments were measured by non-drug and drug-loaded nanoparticles. These results demonstrate that these non-drug micelles was practically non-toxic, moreover, drug-loaded nanoparticles were capable of delivering drugs into cell nucleus and showing high antitumor activity.