Study On Controlled Release Of Epirubicin In Drug Delivery System And Self-assembly Of Polylactide In Emulsion

Cancer is a main disease to threat the health of human being. Chemical therapy is an important method to treat it comparing with operation and radial therapy. Epirubicin is an anthracycline antibiotic and antitumor epimer of doxorubicin that has been used to treat a wide range of cancers. At equimolar doses epirubicin is less myelotoxic than doxorubicin and has a lower incidence of cardiotoxicity. Clinicly, the main medicament is lyophilized power and has severe side effect. To solve the shortcoming of clinic medicament, we develop a novel medicament of epirubicin with controlled release profile.Polylactide (PLA) has received great attention in recent years due to its good biocompatibility, biodegradability, and potential applications in the medical field. In the fields of macromolecular crystalline, polymerization for stereocontrol and self-assembly of amphiphilic block copolymers, crystal PLA has attracted much attention. However, amorphous PLA (PDLLA) is used in drug delivery system at large scale.To develop a drug delivery system of epirubicin, we prepared PDLLA microspheres containing epirubicin with double emulsion-solvent evaporation method. The sizes of the microspheres are ca. 2-5μm, the drug loading and encapsulation efficiency reach ca. 4.39 % and ca. 37.2 %, respectively. Epirubicin is slow and pseudolinear release after an initial burst. Furthermore, we attempt to prepare collagen films containing epirubicin in order to reduce the burst release.In the field of macromolecular self-assembly, we prepared a series of self-assembled aggregates from polylactide in double emulsion system and investigated the morphologies and crystal properties of PDLLA. We observed that PDLLA self-assembled microarchitectures ranged from stick- to star-like aggregates, from sheaf-like to hexapod aggregates with the amount of glycerol increasing in the external aqueous phase. Moreover, the sticks and sheaves are polycrystalline. We further investigated the effect of various concentration of epirubicin on the self-assembly of PDLLA. The microarchitecture is also sheaf-like morphology and polycrystalline. Meanwhile, we also investigated the self-assembly of PDLLA with glycerol and epirubicin coexisted in emulsion. The results are similar to those PDLLA self-assembled microarchitectures induced by glycerol solely.Conclusions: we have exploited a novel medicament of epirubicin with controlled release profile. On the other hand, we studied the self-assembly of PDLLA in double emulsion system deeply and observed some interesting phenomena with various self-assembled microarchitectures of lactide-based polymers. We also extend the self-assembly of macromolecules from amphiphilic block or graft copolymers to general polymers, from crystal polymers to amorphous polymers.