Polymer-Curcumin Conjugate Micelles For PH-Sensitive Drug Delivery

Polymer micelles has a wide application in terms of solubilization of insolubledrugs, but it remains to be further studied in controlling drug release. In this research,considering the environmental stimuli responsive character, the intelligent polymermaterial was combined to micelles to develop two pH sensitive micelles, which had agreat significance in controlling drug release rate, improving drug concentration intarget site and enhancing the bioavailability.Acid-sensitive hydrazone bond was introduced to the amphiphilic block polymermPEG-PLA in this research. Then by controlling different ratios the polymer wascombined to the carbonyl modified curcumin, after that, self-assembling in aqueoussolution to form two kinds of pH sensitive micelles: mPEG-PLA-NHN=Cur thesingle-stranded micelles and Bi(mPEG-PLA-NHN)=Cur the double chain micelles.The structure of the monomers were confirmed by1H-NMR and the curcumingraft ratio of mPEG-PLA-NHN=Cur and Bi(mPEG-PLA-NHN)=Cur were85%and82%respectively according to the peak area. The CMC were8.899±0.721and5.252±0.908μg/mL, which meaned a good diluted stability. The size and morphology werealso characterized, which showed a size about90nm and PDI less than0.3with aspherical uniform distribution and a good dispersibility which is conducive to passivetargeting effect. Furthermore, the micelles showed no hemagglutinating andhemolysis phenomenon indicating the good biocompatibility.The drug loading and releasing experiments showed that affected by themolecular weight, the drug loading efficiency of the single chain micelles (8.56%±0.54%) doubled compared to the double-stranded micelles (3.60%±0.42%), and thedrug contents increased with further encapsulating curcumin physically. Thecumulative curcumin release rate of the two kinds of micelles at pH5.0weresignificantly higher than pH7.4, fully proved the pH-sensitive character of thehydrazone bond, and demonstrated that the acidic environment can trigger a rapidrelease of the drug which consistent with the experimental expectations.The cell cytotoxicity and cellular uptake experiments were conducted on Helacells, the results showed that compared with the double chain micellesBi(mPEG-PLA-NHN)=Cur, mPEG-PLA-NHN=Cur the single-stranded micelles had a greater cytotoxicity and cellular uptake ability, and the results of both micellesenhanced after physically encapsulating more curcumin in the hydrophobic core.Meanwhile, curcumin was mainly distributed in the cytoplasm and cell membraneafter uptaken by the Hela cells.In conclusion, the pH-sensitive curcumin micelles is expected to become a carrierfor controlled release of anti-cancer drugs, and have a broad prospects in theapplication of anticancer drug delivery systems.