Research On PEGylated Biodegradable Polyesters As Drug Carriers

In this paper, several kinds of PEGylated biodegradable polyesters were designed and synthesized. Their structures and characters were characterized. The pharmaceutical capabilities of these polyesters as anti-cancer drug carriers were also investigated.A convenient pathway to control drug release from copolymer nanoparticles (NPs) by hybrid assembly of different kinds of copolymers was investigated in this paper. Three kinds of biodegradable amphiphilic copolymers, Methoxy poly(ethylene glycol)-block-poly(L-lactic acid) (PELLA), methoxy poly(ethylene glycol)-block-poly (D,L-lactic acid) (PEDLLA) and poly(ethylene glycol)-block-poly(caprolactone)- block -poly(ethylene glycol) (PECL) were prepared and used to assemble into hybrid nanoparticles (HNPs) as carriers of paclitaxel. The structure and properties of the paclitaxel loaded copolymer NPs and HNPs were characterized by DSC, WAXD, TEM and light scattering. The results show that small spherical HNPs (diameter < 100 nm) with good paclitaxel loading ability and entrapping efficiency were obtained simply by hybrid assembling different copolymers. The in vitro release studies indicate that paclitaxel release rate can be controlled easily by varying the ratio of the hydride copolymers. The release control mechanism of the HNPs is mainly due to the crystallization adjustment by mixing of PEDLLA into PELLA or PECL. The HNPs provide a convenient approach to control drug release for drug-loaded NPs.PEGylated poly(ester-sulfide)s (DPEGs) were synthesized by condensation polymerization of dithiols and poly(ethylene glycol) diacrylates (PEGDA) or dimethacrylates (PEGDMA). These DPEGs carried functional groups such as terminal thiol or (meth)acrylate groups and pendant hydroxyl groups. Using these functional groups can successfully react with anti-cancer drug camptothecin to form poly-drug conjugate, and connect targeting group folic acid to the end groups of polymer. With different ratio of polymer and drug in conjugation reaction, polymer chain can carry different amount of drugs. The synthesized polymer-drug conjugates have cancer sensitivity, while polymers do not have. DPEGs are pH-dependent degradable. They are stable at pH 7.4 but degraded quickly in acid condition (pH=6.0, 5.0). DPEGs have thermoresponsibility and the phase transition ranges sharp. With changing the PEG chain length, the type of the double bond and the type of dithiol, phase transition temperature can be adjusted. There are two polymers have LCSTs at 36°C and 39°C, respectively, close to the body temperature which make them have promising application potential. Crosslinking DPEG chains produced thermoresponsive hydrogels. And the hydrogels prepared by end-capping method maintain the thermoresponsive properties of the DPEGs.PEGylated polycarbonates (PEG-DA) were synthesized by condensation polymerization of PEG and dianhydride. This kind of polymers is connected by ester bond and there is a free carbonic acid group near ester bond. Under acid circumstances (pH=6.0,5.0), polymers are hydrolysized quickly by the attack of acid group. PEG-DA can effectively conjugate anti-cancer drugs (camptothecin, cisplatin). With different ratio of polymer and drug in conjugation reaction, polymer chain can carry different amount of drugs. The synthesized polymer-drug conjugates have cancer sensitivity, while polymers do not have.