Synthesis, Properties And Controlled Release Behaviors Of β-Cyclodextrin Contained Hyperbranched Polyamidoamine

Researches in new drug carriers and controlled release systems for drug delivery are the principal pathways to achieve the goals of improving the release pattern, decreasing the toxicity, increasing the absorption and the therapy effect of drugs. Hyperbranched polyamidoamines (HPMAs) possess high solubility, threedimensional structure, empty internal cavities and many terminal functional groups. These specific properties make HPMAs be capable of chelating different matellic ions, encapsulating various molecules, and having excellent biocompatibility.β-cyclodextrin (β-CD) is a cyclic oligosaccharide with a relative hydrophobic central cavity, which can form complexes with appropriate drug molecules via noncovalent interactions to improve the physicochemical properties of drugs, such as solubility, stability and bioavailability, and reduce their toxicity and suppressing unpleasant taste or smell. In this thesis, we will combine the advantages of HPMA andβ-CD to synthesize some novel hyperbranched drug carriers, which not only can increase the solubility of drugs in water, but also can adjust the loading capacity and release rate of drugs. The two aspects of our research are described in detail as followed:One is the synthesis and characterization ofβ-Cyclodextrin contained hyperbranched polyamidoamines (HPMA-β-CDs). As a control, the pure HPMA were synthesized firstly by the Michael addition polymerization of 1-(2-aminoethyl) piperazine (AEPZ) and N,N'-methylene bisacrylamide (MBA) with the equimolar ratio. And then, three HPMAs containing various amounts ofβ-CD (HPMA-β-CDs) were also prepared by the same produce as the pure HPMA except that a part of AEPZ was instead of Ethylenediamine/β-CD (EDA-β-CD), which was the resulting product ofβ-CD modified by the sulfonylation of p-toluensulfonyl chloride and the amination of ethylenediamine. The obtained HPMA-β-CDs were characterized detailedly by Nuclear Magnetic Resonance (NMR), Differential Scanning Calorimetry (DSC), Dynamic light scattering (DLS) and Tourier Transform Infrared Spectroscopy (FTIR). The results indicated thatβ-CD could be introduced into HPMA successfully and formed as not only the terminal unites but also the linear units in HPMA-β-CDs. In addition, the glass transition temperatures (Tg) of HPMA-β-CDs increased evidently with the amount ofβ-CD moiety increasing, they are 29.8, 32.1, 45.7 and 59.9 oC corresponding to the moar percents ofβ-CD (0%,2.5%,5% and 10%) respectively. The cytotoxicity tests also confirmed the excellent biocompatibility of HPMA and HPMA-β-CDs and can be used as drug carriers.The other aspect is that chlorambucil (CLB, an anti-cancer drug) was used as a model drug and loaded into HPMA-β-CDs via the solution method and then the controlled release behavior of them were investigated in vitro in the buffer solutions with different pH value. First, the half-and-half of CLB and HPMA-β-CDs in weight was dissolved in ethonal to load the CLB into HPMA-β-CDs. The resulting CLB loaded HPMA-β-CDs were characterized by DSC and NMR. Second, the release process of CLB from HPMA-β-CDs at the different pH value was monitored by the Ultraviolet spectra (UV) at the wavelength of 255nm. The results indicated that the CLB molecules were included into HPMA-β-CDs successfully and the interaction between CLB and HPMA-β-CDs was on the molecular lever. The HPMA-β-CDs as drug carriers could increase the solubility of CLB in water and the drug capacity of HPMA-β-CDs also increased evidently with the amount ofβ-CD moiety increasing, they were 27.5,33.0,41.5 and 50.0% corresponding to the moar percents ofβ-CD (0%,2.5%,5% and 10%) respectively. It was found the release rate of CLB could be slowed up due to the encapsulation of the hydrophobic inner cavity inβ-CD to CLB. However, the cumulative amount of the CLB released from HPMA-β-CDs reached almost 100% after 50 hours when the pH value of the buffer solution was of 9.7. This may be attributed to the ionization of the carboxyl group in CLB, the interaction between CLB molecules and HPMA-β-CD-1 was reduced and resulted in the CLB releasing completely.