<p>Co-Delivery of Paclitaxel and Doxorubicin by pH-Responsive Prodrug Micelles for Cancer Therapy</p>

Abstract

Background: It is of great significance to develop intelligent co-delivery systems for cancer chemotherapy with improved therapeutic efficacy and few side-effects. Materials and Methods: Here, we reported a co-delivery system based on pH-sensitive polyprodrug micelles for simultaneous delivery of doxorubicin (DOX) and paclitaxel (PTX) as a combination chemotherapy with pH-triggered drug release profiles. The physicochemical properties, drug release profiles and mechanism, and cytotoxicity of PTX/DOX-PMs have been thoroughly investigated. Results and Discussion: The pH-sensitive polyprodrug was used as nanocarrier, and PTX was encapsulated into the micelles with high drug-loading content (25.6%). The critical micelle concentration (CMC) was about 3.16 mg/L, indicating the system could form the micelles at low concentration. The particle size of PTX/DOX-PMs was 110.5 nm, and increased to approximately 140 nm after incubation for 5 days which showed that the PTX/DOX-PMs had high serum stability. With decrease in pH value, the particle size first increased, and thenwas no longer detectable. Similar change trend was observed for CMC values. The zetapotential increased sharply with decrease in pH. These results demonstrated the pHsensitivity of PTX/DOX-PMs. In vitro drug release experiments and study on release mechanism showed that the drug release rate and accumulative release for PTX and DOX were dependent on the pH, showing the pH-triggered drug release profiles. Cytotoxicity assay displayed that the block copolymer showed negligible cytotoxicity, while the PTX/ DOX-PMs possessed high cytotoxic effect against several tumor cell lines compared with free drugs and control. Conclusion: All the results demonstrated that the co-delivery system based on pH-sensitive polyprodrug could be a potent nanomedicine for combination cancer chemotherapy. In addition, construction based on polyprodrug and chemical drug could be a useful method to prepare multifunctional nanomedicine.

Evaluation of the efficacy and safety of a new formulation‐lipid emulsion‐based PTX injection: Pharmacokinetics, tissue distributions and anticancer effect on human gastric cancer cells in vitro

“…Since PTX is highly lipophilic and poorly soluble in water, several new formulations have been investigated which can confer beneficial effects on its pharmacology and toxicology (Jiang et al, 2020;Kitayama et al, 2017;Yang et al, 2020). However, the components of an intravenous formulation may affect the clearance, protein binding and distribution of the drug.…”

Fabrication of pH/Redox Dual-Responsive Mixed Polyprodrug Micelles for Improving Cancer Chemotherapy

“…The in vitro DOX release profiles from MPPMs at different conditions was investigated by the dialysis method, following previous references with few modifications (Zhang et al, 2016;Men et al, 2019;Jiang et al, 2020). Briefly, 6 mg of MPPMs were dispersed in 6 ml of respective PBS in a dialysis bag (MWCO, 3,500 Da) at a concentration of 1 mg/ml.…”

Intelligent Drug Delivery by Peptide-Based Dual-Function Micelles

“…Many methodologies were studied to improve the delivery efficiency of anticancer drugs, among which the preparation of polymeric micelle drugs is a promising strategy for achieving this goal [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. Compared with conventional anticancer drugs, prodrug micelles prepared by nanomedicine have some advantages, such as, improving the pharmacokinetics and accumulation of drugs at the tumor site, increasing the bioavailability of drugs, and reducing the side effects of drug toxicity on the organism [ 15 , 16 , 17 ]. To prolong the circulation time of drug carriers in vivo, polyethylene glycol (PEG) modification and other modifications are often exploited in the designing of drug carriers, which could be passively enriched at the tumor site based on the EPR effect [ 18 , 19 ].…”