pH-responsive micelles based on (PCL)2(PDEA-b-PPEGMA)2 miktoarm polymer: controlled synthesis, characterization, and application as anticancer drug carrier

Abstract

Amphiphilic A2(BC)2 miktoarm star polymers [poly(ϵ-caprolactone)]2-[poly(2-(diethylamino)ethyl methacrylate)-b- poly(poly(ethylene glycol) methyl ether methacrylate)]2 [(PCL)2(PDEA-b-PPEGMA)2] were developed by a combination of ring opening polymerization (ROP) and continuous activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP). The critical micelle concentration (CMC) values were extremely low (0.0024 to 0.0043 mg/mL), depending on the architecture of the polymers. The self-assembled empty and doxorubicin (DOX)-loaded micelles were spherical in morphologies, and the average sizes were about 63 and 110 nm. The release of DOX at pH 5.0 was much faster than that at pH 6.5 and pH 7.4. Moreover, DOX-loaded micelles could effectively inhibit the growth of cancer cells HepG2 with IC50 of 2.0 μg/mL. Intracellular uptake demonstrated that DOX was delivered into the cells effectively after the cells were incubated with DOX-loaded micelles. Therefore, the pH-sensitive (PCL)2(PDEA-b-PPEGMA)2 micelles could be a prospective candidate as anticancer drug carrier for hydrophobic drugs with sustained release behavior.

Fabrication of PDEAEMA-based pH-responsive mixed micelles for application in controlled doxorubicin release

“…Among them, PDEAEMA is a brush pH-responsive polymer with a pendant tertiary amine as its responsive group and pK a of about 6.9, and has been successfully used in anticancer drug delivery systems in the form of diblock, triblock or even more complex amphiphilic polymeric micellar structures. [18][19][20][21][22][23] However, the drug loading efficiency and well-controlled drug release of these polymers still need to be improved. Especially, suitable methods to enhance the drug loading content (LC) and drug entrapment efficiency (EE), and at the same time, achieve pH-targeting drug release with a low initial burst release are urgently required.…”

Co-Delivery of Imiquimod and Plasmid DNA via an Amphiphilic pH-Responsive Star Polymer that Forms Unimolecular Micelles in Water

“…The blank and IMQ-loaded micelles were prepared using the diafiltration method [33][34][35]. To prepare IMQ-loaded micelles, IMQ (8 mg) was dissolved in 10 mL of DMSO.…”

Quantitative Structure-Property Relationship (QSPR) Modeling of Drug-Loaded Polymeric Micelles via Genetic Function Approximation

“…Fifteen kinds of designed polymers were synthesized in our laboratory. Drug-loaded micelles were prepared using two DOX/polymer ratios (10/40 and 20/40 (mg/mg)), resulting in 30 data LC datasets (LC datasets were transformed using natural logarithms (ln) to better conform to the normal distribution), as shown in S1 Table [ 36 – 38 ]. All LC data were measured in aqueous solution at pH 7.4 and room temperature.…”