pH-responsive polymeric micelles self-assembled from amphiphilic copolymer modified with lipid used as doxorubicin delivery carriers

Abstract

In the present study, a novel pH-responsive amphiphilic copolymer, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)] conjugated poly(β-amino esters) (DSPE-b-PEG-b-PAE-b-PEG-b-DSPE), was designed and successfully synthesized via Michael-type step polymerization. The chemical structure of the pentablock copolymer was confirmed with proton nuclear magnetic resonance (1H-NMR) and Fourier transform infrared (FT-IR) spectroscopy. The copolymer was able to self-assemble into core/shell polymeric micelles in aqueous solution at low concentrations, and its critical micelle concentration (CMC) value was 4.5 mg l−1 determined by fluorescence spectrophotometry. The pKb value of the copolymer was about 6.5, confirmed by acid–base titration, indicating the pH-sensitivity of the polymeric micelle. The hydrodynamic diameter, distribution and zeta potential of the polymeric micelles at different pH conditions were monitored by dynamic light scattering (DLS). Doxorubicin (DOX) was encapsulated into the core of the micelles with a high drug loading content (15.9%) and entrapment efficacy (60.4%). In vitro experiments demonstrated that the release behaviour of DOX from the DOX-loaded polymeric micelles (DOX-PMs) was pH-triggered. When the pH decreased from 7.4 to 5.0, the drug release rate was markedly accelerated. MTT assay showed that the copolymer had negligible cytotoxicity whereas the DOX-PMs displayed high toxicity for tumour cells such as B16F10, HepG2 and HeLa cell lines. The results demonstrated that these pH-sensitive polymeric micelles could be used as potential anti-cancer drug carriers for cancer chemotherapy with controlled release.

Microcarriers for Upscaling Cultured Meat Production

“…Micro-encapsulation and sustained release of bioactive molecules is a field vastly researched for food applications (53,54) and the same principles can apply for microcarrier based cell culture for meat production. Temperature and pH cues can also be applied to control the in vitro release kinetics from loaded microcarriers (55,56).…”

Hyaluronic Acid-Coated Nanomedicine for Targeted Cancer Therapy

“…PMs, which are amphiphilic, can encapsulate small hydrophobic drugs in their hydrophobic core via physical, chemical and electrostatic interaction [15,16,17], and can deliver hydrophobic drugs into their destinations [18]. Thus, PMs could improve the efficiency of anticancer drugs by enhancing drug solubility in water, prolonging blood circulation time, and selectively accumulating at the tumor via the EPR effect [19,20,21]. The nanosized (20 ~ 100 nm) structure of the PMs enables them to preferentially accumulate in angiogenic tumor tissues through the fenestrate vasculature following systemic administration [19,22].…”

Recent Advances in Nanocarrier-Assisted Therapeutics Delivery Systems

“…For example, vaccines for hepatitis B virus are under development using pH-responsive liposomes to achieve cytosolic drug release [91]. Polymeric micelles that are functionalized to be pH-responsive are under active investigation for their application in chemotherapy [92,93]. To overcome certain disadvantages of some pH-sensitive polymers, such as uncontrolled drug-loading or drug-releasing rate as well as undesired toxicity, non-polymer pH-sensitive carbon dots were also developed for cancer therapy [94].…”