Amphiphilic miktoarm star copolymer (PCL)3-(PDEAEMA-b-PPEGMA)3 as pH-sensitive micelles in the delivery of anticancer drug

Abstract

Well-defined A 3 (BC) 3 type amphiphilic miktoarm star polymers poly(3-caprolactone) 3 -[poly (2-(diethylamino)ethyl methacrylate)-b-poly(poly(ethylene glycol) methyl ether methacrylate)] 3 [(PCL) 3 -(PDEAEMA-b-PPEGMA) 3 ] and their pH-sensitive self-assembled polymeric micelles were developed as anticancer vehicles for improved cancer therapy. These miktoarm star polymers were synthesized by a combination of ring opening polymerization (ROP) and continuous activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) and characterized by GPC and 1 H NMR measurement. The CMC values of the miktoarm star polymers in aqueous solution were extremely low (0.0029-0.0035 mg mL À1 ), suggesting that the micelles are relatively stable in solution. The selfassembled blank and doxorubicin (DOX)-loaded micelles were spherical in morphology with average sizes of 110-240 nm depending on the architecture of the copolymers, which were determined by transmission electron microscopy (TEM) and dynamic light scattering (DLS). When decreasing pH from 7.4 to 5.0, the micelles underwent globule-uneven-extended conformational transitions, and in vitro drug release rates were significantly accelerated, owing to the swelling of micelles at lower pH conditions caused by the protonation of tertiary amine groups of DEAEMA. Moreover, the drug release profiles at different pH values were well fitted by a semi-empirical equation. The in vitro cytotoxicity of DOX-loaded micelles against HepG2 cells suggested that DOX-loaded (PCL) 3 -(PDEAEMA-b-PPEGMA) 3 micelles exhibited similar anti-tumor activities to free DOX, with at least 80% decrease in cell viability after 48 h incubation. Intracellular uptake demonstrated that DOX was delivered into the cells effectively after the cells were incubated with DOX-loaded micelles. The results demonstrated that the pHresponsive (PCL) 3 -(PDEAEMA-b-PPEGMA) 3 micelles could be used as latent vehicles for delivering hydrophobic anticancer drugs with controlled and sustained release behavior.

Polyurethane/Poly(2-(Diethyl Amino)Ethyl Methacrylate) blend for drug delivery applications

“…Blends have many applications, but in particular they are being proposed for using in drug delivery based on polymers [2][3][4] ; or on composites [5] . pH-sensitive systems are a particular case and several materials were proposed for preparing them, including silica particles [6,7] , other inorganic particles [8] , polymeric blends [9][10][11][12] , copolymers [13][14][15] and hybrid materials [16,17] .…”

Poly(2-(diethylamino)ethyl methacrylate)-based, pH-responsive, copolymeric mixed micelles for targeting anticancer drug control release

“…The zeta potential increased slightly from pH 3.0 to 4.5, presumably correlated to the higher degree of micellar aggregation. 18 The zeta potential reached a maximum of 25 mV at pH 4.5. Further pH increased gradually deprotonated the DEAEMA segment, leading to the decrease in the micellar zeta potential.…”

“…The dried micelles were stored at −20°C until further experiments. The method to determine the drug-loading content (LC) and entrapment efficiency (EE) was reported in our previous works, 17,18 and the detail procedure is shown in the Supplementary materials.…”

“…[15][16][17][18] In particular, pH-responsive polymeric micelles are selfassembled by triblock or multi-block copolymers containing hydrophilic blocks, hydrophobic blocks and functional response blocks. A substantial proportion of hydrophilic/ hydrophobic block in the micelles structure improved the in vivo micelle stability and drug-loading capability but at the price of the reduced micellar pH responsiveness.…”

“…17,18,[40][41][42][43] Equation 1 was used to fit the drug release profiles, with n indicating the drug release mechanism and k reflecting the rate constant of the DOX release. The release process of the three DOX-loaded micelles can be divided into two stages, with the first stage from 0 to 12 h and the second stage between 12 and 96 h. The linear fitting curves of micelle I, mixed micelle II and mixed micelle III are shown in Figure 8A-C, respectively, and the fitting parameters are listed in Table 3.…”