Comparison of drug delivery properties of PEG-b-pdhpc micelles with different compositions

Abstract

An anti-tumor drug doxorubicin was encapsulated in micelles of poly(ethylene glycol)-b-poly(2,2-dihydroxylmethyl propylene carbonate) (PEG-b-PDHPC) diblock copolymers. The morphology of both blank micelles and drug loaded micelles was characterized by TEM. The in vitro drug release profiles of micelles were investigated. The cytotoxicity of the micelles was evaluated by incubating with Hela tumor cells and 3T3 fibroblasts. The drug loaded micelles were co-cultured with HepG2 cells to evaluate the in vitro anti-tumor efficacies. The results showed that the mean sizes of both micelles with different copolymer compositions increased after being loaded with drugs. The drug release rate of PEG 45 -b-PDHPC 34 micelles was faster than that of mPEG 114 -b-PDHPC 26 micelles. Both of the two block copolymers were non-toxic. The confocal laser scanning microscopy and flow cytometry results showed that both the drug loaded micelles could be internalized efficiently in HepG2 cells. The PEG 45 -b-PDHPC 34 micelles exhibited higher anti-tumor activity comparing to mPEG 114 -b-PDHPC 26 micelles.

Enhanced endocytosis of acid-sensitive doxorubicin derivatives with intelligent nanogel for improved security and efficacy

“…2,3 However, further application of DOX has been hampered by its serious side effects including gastrointestinal disorders, bone marrow toxicity, alopecia, stomatitis, acute and cumulative cardiotoxicity as well as extravasation. 4 In order to circumvent these limitations and expand the therapeutic potential of DOX, various approaches have been applied, such as chemical modification 5 and loading the drug molecules into nanocarriers including polymeric micelles, [6][7][8][9][10][11] vesicles, [12][13][14][15] liposomes 16,17 and nanogels. [18][19][20] Chemical modification of DOX is an important approach for the development of prodrugs that overcome the side effects.…”

A novel nanoassembled doxorubicin prodrug with a high drug loading for anticancer drug delivery

“…Furthermore, polyethylene glycol has been a widely used polymer carrier for drug delivery since it has been approved for clinical use. [24][25][26] DOX has been graed to a macromolecular carrier via an acid-labile hydrazone bond, which is known to be sufficiently stable at pH 7.4 but readily cleavable in an acidic environment such as in endo-lysosomes. [27][28][29][30] Notably, the MPEG-b-DOX copolymers could selfassemble into micelles in aqueous solutions, not only making use of enhanced permeability and retention effect but also largely simplifying production.…”

Self-assembling doxorubicinprodrug forming nanoparticles for cancer chemotherapy: synthesis and anticancer study in vitro and in vivo

“…Moreover, PEG is a well-known and widely used polymer carrier for drug delivery since it has been approved for clinical use. [30][31][32][33] Particularly, modication with PEG (PEGylation) has been shown to signicantly improve the physicochemical and biological properties of various drug delivery systems. [34][35][36] Furthermore, DOX is conjugated with PEG via a hydrazone bond, a well-known pH-responsive bond, 37,38 which may induce faster release of DOX in an acidic environment (e.g.…”