Synthesis and evaluation of amphiphilic scorpion-like and star macromolecules for biomedical applications.

摘要

Self-assembled and unimolecular amphiphilic macromolecules with pseudo-double branched and single tails were synthesized. Degradation behavior, drug loading efficiency, drug release rate and stability of macromolecules were investigated. The anti-tumor drug, Camptothecin and the anti-inflammatory drug, Indomethacin were used to evaluate drug loading and release efficiency. Unimolecular amphiphilic macromolecules were more stable in the presence of the enzyme, lipase and human serum albumin (HSA) compared to self-assembled macromolecules. Pseudo-branched macromolecules drug release rate was slower compared to linear macromolecules.;Furthermore, self-assembled single tail amphiphilic macromolecule (AScMs) were modified to achieve active tumor targeting and to achieve high concentration of drug with cyclo(RGDfk) and Doxorubicin, respectively. Cyclo(RGDfk) conjugated AScMs showed higher uptake in tumor cells compared to AScMs alone. Furthermore, AScMs and Cyclo(RGDfk)-AScMs showed similar uptake profile with healthy cells. Higher loading efficiency was determined in Doxorubicin conjugated AScMs. On the other hand, lower IC50 value (high toxicity) was determined by AScMs-Dox conjugation.;Self-assembled pseudo branched macromolecules were modified with two carboxylate acids to achieve higher Low Density Lipoprotein (LDL) uptake. LDL uptake of branched macromolecules was compared with linear self-assembled macromolecules which are modified with carboxylic acid and sulfuric acid by our group members. Two carboxylate acid conjugated-AScMs (2CM branched) achieved the highest LDL uptake compared to other macromolecules.