The Synthesis Of Novel Pendent Functional Aliphalic Polyester And Preparation Of Its Anti-tumor Prodrug

Poly(lactide)(PLA) is a type of biodegradable and biocompatible polymer frombiorenewable feedstock. PLA has been attracting considerable attention due to itsnontoxicity, good bioavailability, and biocompatibility, which allows for applicationsin the field of drug delivery, controlled release and tissue engineering. However, theapplication of PLA is hampered due to its hydrophobic and semicrystalline propertiesand the absence of functional moieties that can be used for tailoring physicalproperties and introducing bioactive moieties. There are two approaches to preparefunctional PLA analogs: polymerization of specifically designed monomers orpost-modification.Thus, in this contribution, norbornene-functional poly(lactide)s were prapared andutilized as multireactive polymeric scaffolds to prepare a series of functional PLAsvia thiol-ene click reaction,1,3-dipolar cycloaddition, and epoxidation reaction. Inaddition, amphiphilic block copolymers have been extensively used to prepareself-assembled polymer micelles for drug delivery. The most widely employedhydrophilic block is poly(ethylene glycol)(PEG), which is FDA-approved, and it issoluble in water. Drug-loading of micelles are mainly two forms: one is physicalencapsulation, another is chemical bond. Using chemical bond method to avoid thecritical interpretation of the drugs, which can effectively control the drug release,improve the utilization rate of the drug. The main contents are as follows:1.A series of functional PLAs containing hydroxyl, carboxyl pendant groups areprepared via UV-initiated thiol-ene click reaction. Oligo(ethylene glycol)(OEG)grafts polymer is prepared via the heat promoted1,3-dipolar cycloaddition reaction.The norbornene side groups can be readily oxidized using m-chloroperoxy benzoicacid (mCPBA) to yield the corresponding epoxidated polymers.1H NMR,13C NMR,FTIR, and GPC were used to investigate.2.Amphiphilic block copolymer bearing pendant carboxyl groups based on MPEGhydrophilic chain segment is synthesised. And paclitaxel prodrug is prepared byconjugating paclitaxel onto the hydrophobic chain segments via ester bonds. Allpolymers were characterized by1H NMR, FTIR and GPC.3.Fully biodegradable Poly(ε-caprolactone)-paclitaxel prodrugs were determined byMTT assay, confirmed that the materials-Poly(ε-caprolactone) displayed low cytotoxicity and good biocompatible, and the invitro antitumor effects of the prodrugson A549and MCF-7cells were similar to the free PTX after48h incubation. Theseresults suggested that the P(α-C2CL)-PTX prodrugs possess great antitumor abilitytoward an efficient drug delivery system.