Synergistic dual-pH responsive copolymer micelles for pH-dependent drug release

Abstract

The tuning of the structure of nanocarriers with fast acidic-degradation rate and high stability in physiological conditions or during storage is under intensive study. In this context, a kind of dual-pH responsive micelles with well-balanced stability, that is, fast hydrolysis in acidic environment and stability towards blood drug release at 7.4 were developed. This is achieved by the self-assembly of micelles of poly(ethylene glycol)-b-(poly ε-caprolactone-g-poly(2,2-dimethyl-1,3-dioxolane-4-yl)methylacrylate-co-2(dimethylamino)ethyl methacrylate) (mPEG-b-(PCL-g-P(DA-co-DMAEMA))) copolymers with two inert pH responsive moieties of DA and DMAEMA. The fast synergistic acid-triggered disassembly and high stability at physiological condition of the mPEG-b-(PCL-g-P(DA-co-DMAEMA)) micelles was verified by (1)H NMR, particle size and optical stability measurements, which was induced and mediated by the synergistic pH responses of the hydrolysis of the ketal in DA moieties and the switch in solubility of tertiary amino moieties (DMAEMA) under mild acid conditions. It was observed that the hydrolysis rate of the ketal could be promoted by increasing the content of DMAEMA moieties. The fast intracellular disassembly of the micelles depending on the contents of DMAEMA moieties was also traced by fluorescence resonance energy transfer (FRET). The in vitro release studies showed that the release of DOX from mPEG-b-(PCL-g-P(DA-co-DMAEMA)) micelles at mild acid condition was significantly accelerated by increasing the content of DMAEMA moieties, while greatly impeding drug release in physiological conditions. The antitumor activity of DOX-loaded micelles was studied in MCF-7 and 4T1 cells in vitro and in 4T1 tumor-bearing Balb-c mice in vivo. The results indicated the DOX-loaded micelles with higher content of DMAEMA moieties exhibited enhanced anticancer activity. Collectively, the synergistic dual-pH responsive design of mPEG-b-(PCL-g-P(DA-co-DMAEMA)) micelles provided a new route for improving anticancer drug delivery efficiency.

Doxorubicin conjugated carbon dots as a drug delivery system for human breast cancer therapy

“…Figure A shows the drug release profile of the CDs‐DOX complexes in the drug release media with different pH values. Obviously, the CDs‐DOX complexes exhibited a pH‐sensitive drug release property, which was probably due to the better solubility of DOX in acidic solution . The CDs‐DOX complexes as pH‐sensitive carriers might be in favour of promoting the efficiency of releasing drugs with the acidic environment of tumours.…”

Novel amphiphilic glucose-responsive modified starch micelles for insulin delivery

“…The stability of the dialdehyde starch derivative micelles was measured by DLS because the physiological stability of polymeric micelles is of importance for long-term storage, transportation, and scalable processing in drug carrier applications. 51 Because the micellar structure is susceptible to exposure of the hydrophobic core, the 40% mPEG-DAS-APBA and mPEG-DAS-APBA-Cou micelles showed a slight increase in particle size aer 8 h and 24 h due to the appearance of abundant aggregation of the cores. Compared with the 40% mPEG-DAS-APBA micelles, the mPEG-DAS-APBA-Cou micelles indicated preferable stability.…”

Photosensitive Nanoparticles Combining Vascular‐Independent Intratumor Distribution and On‐Demand Oxygen‐Depot Delivery for Enhanced Cancer Photodynamic Therapy

“…In this study, poly(ethylene glycol) (PEG)-poly(ε-caprolactone) (PCL) was used as the drug delivery system for its biocompatibility and biodegradability. [24][25][26] IR-780 was chosen as a typical example of photosensitizer, which was a near-infrared (NIR) absorbing fluorescence dye with higher stable fluorescence intensity. [27][28][29] Perfluorooctyl bromide (PFOB), an artificial blood substitute with higher oxygen storage capacity and good biocompatibility, [30,31] was incorporated into the PEG-PCL NPs together with IR780 serving as an oxygen supplier.…”