Novel Polymeric Vesicles with pH‐Induced Deformation Character for Advanced Drug Delivery

Abstract

pH-responsive amphiphilic graft macromolecules consisting of a polyphosphazene backbone, hydrophilic PEG branches and pH-sensitive DPA were successfully synthesized and characterized. The copolymer can self-assemble into vesicles in an aqueous solution with unique inner structure and homogeneously encapsulate both lipophilic and hydrophilic molecules. The pH-dependent structure change of vesicles was also observed by DLS and TEM. Dox-loaded vesicles exhibit a sharp pH-responsive drug release profile and dramatically enhance the cytotoxicity of Dox against Dox-resistant MCF-7/adr cells. These results suggest such vesicles based on pH-responsive polyphosphazene hold great potential for specific drug therapy.

Self-assembly and morphological transitions of random amphiphilic poly(β-d-glucose-co-1-octyl) phosphazenes

“…[32][33][34][35][36] Recently, the combination between the polyphosphazene modification and thiol-ene reaction, which allows for the preparation of well-defined materials with few structural limitations and synthetic requirements, 37 not only greatly enhances reaction efficiency, but also leads to polyphosphazene with a controlled functional degree. Zheng et al 49 designed a pH-responsive polyphosphazene, which was prepared by linking N,N-diisopropylethylenediamine (DPA) onto a backbone of PEGylated polyphosphazene, for cytoplasmic release of doxorubicin in Dox-resistant tumor cells. The whole synthetic process was carried out under mild conditions and heavy metal free conditions.…”

Dual-Layered Nanogel-Coated Hollow Lipid/Polypeptide Conjugate Assemblies for Potential pH-Triggered Intracellular Drug Release

“…Although these nanovehicles show promise in selective delivery of therapeutic agents to target sites, several intractable problems (e.g., the premature drug leakage from carriers and poor intracellular drug-release property that lead to an insufficient drug bioavailability for killing cancer cells and undesired side effects) have not been completely overcome yet [7], [8], [9]. In this regard, substantial efforts have been devoted to the development of stimuli-responsive devices as novel drug delivery systems capable of controlling payload release in response to biological stimuli such as temperature [10], [11], pH [12], [13], [14], [15], and redox potential [16], [17], [18]. The stimuli-triggered drug liberation could significantly promote therapeutic efficacy and minimize side effects.…”

“…The stimuli-triggered drug liberation could significantly promote therapeutic efficacy and minimize side effects. Among these stimuli, acidic pH has been frequently adopted as an optimal internal trigger due to the mildly acidic pH existing in tumor tissues and in the intracellular organelles including both endosomes and lysosomes [13], [14]. To achieve the pH-triggered intracellular drug release, various nanovehicles functionalized with pH-responsive structural characteristics have been developed.…”

pH‐Responsive Drug‐Delivery Systems

“…Asian J. 2014, 9, 1 -23 drug-delivery systems based on chitosan, alginate, and pectin, [43] dendronized heparin, [44] polypeptide-based block ionomer complex formed by anionic methoxy poly(ethylene glycol)-b-poly(l-glutamic acid), [45] polyphosphazene backbone with poly(ethylene glycol) branches and pH-sensitive N,N-diisopropylethylenediamine, [46] mixed polymeric micelles based on three grafted copolymers (poly(ethylene glycol)-1,2-distearoylsn-glycero-3-phosphoethanolamine, poly(histidine), and poly(-ethylene glycol)), [47] poly(ethylene glycol)-poly(e-caprolactone)/ folic acid/DOX, [48] and poly(d,l-lactide-co-glycolide)/poly(ethylenimine). [49] In summary, various polymeric materials have been investigated for applications in pH-responsive drug delivery.…”