| Intelligent drug delivery systems have sparked great interest in recent years. How to build intelligent drug delivery systems and develop stimulus response material attracts great attention. Presently, a large mount of work are focused on stimulus response micelles and hydrogels. Supramolecular polymer micelles, based on cyclodextrin (CD)/polymer inclusion, as one of the promising biomaterials, have sparked great interest due to the mild preparation conditions, the simple micellization process, easy to control, injectable, etc. which provides the intelligence required for controlled drug release, biosensors and so on. Besides, based on the oxidative-response feature of ferrocene (Fc), some biocompatible polymer is also attracting people’s attention, which have been widely used in the preparation of an efficient delivery and controlled-release functional biomedical materials.In this paper, we use the inclusion between β-CD (β-Cyclodextrinand, β-CD) and Fc (Ferrocene) prepared supramolecular block copolymer PNIPAAm-β-CD/Fc-mPEG, in which temperature changes can cause morphological changes in PNIPAAm block as follows:below the LCST (lower critical solution temperature), PNIPAAm can hardly dissolve in the aqueous solution, the molecules form a random coil structure; above the LCST copolymers self-assemble into micelles. The dialysis method was employed to prepare blank and drug-loaded micelles. Among them, PNIPAAm is the core as a temperature-sensitivity part, mPEG is the shell as a hydrophilic part, the connection point is a redox-sensitive clathrates β-CD/Fc. Critical micelle concentration (CMC) was measured using the fluorescent probe technique; The temperature-and oxidation-sensitive properties of the micelles solution were investigated by optical transmittance measurement. The morphology and diameter of the polymer micelles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). When the temperature and oxidation environment of the system change gradually, the hydrophilic-hydrophobic property of PNIPAAm and the inclusion property of β-CD/Fc mutations respectively, thus play a role as a two-stage switch in drug release. The entrapment rate and drug-loading rate were determined with dialysis method. The in vitro release study was further performed to examine the temperature and oxidation-responsive drug release behavior from drug-loaded micelles.The results show that the critical micelle concentration (CMC) of the amphiphilic copolymer is0.75mg/ml; the polymer can gradually form micelles at40℃, whose average diameter is150nm in the oxidizing environment and200nm in the reducing environment. MPEG, as the shell of the micelles, can twine hydrophilic drugs through hydrogen bonding while PNIPAAm, as the core of the micelles can wrap hydrophobic drugs. Drug-loaded micelles have no difference with blank ones in shape and size. The DOX-micelles have a drug loading rate of (53.9±3.8)%, single-degree release efficiency (70.7±4.5)%, second-degree release effiencney (33.4±3.4)%,(16.8±3.4)%respectively, total efficiency is (64.38±8.77)%; the TEX-micelles have a drug loading rate of (46.3±4.2)%, single-degree release efficiency (71.4±2.8)%, second-degree release effiencney (28.7±1.8)%,(16.7±1.1)%respectively, total efficiency is (64.8±0.53)%.The innovation of this paper is mainly as follows:1. Using the inclusion feature of β-CD and Fc build a block copolymers to avoid the influence of molecular weight distribution by traditional polymerization methods;2. The micelles was constructed based on the temperature-sensitive feature of PNIPAAm block. Since the differences in temperature in different tissues of the human body has a significant effect on the hydrophilicity of PNIPAAm, the micelles are designed for tumor tissue to intracellular delivery drug and positioning release;3. The ionization effect of polyethylene glycol(PEG) improve the stability of micelles. Based on the oxidation-sensitive P-CD/Fc inclusion, it is easy to adjust the amount of drug released by polymer micelles, which is expected as an injectable material for biomedical applications such as drug delivery. |
PDF Full Text Request