Potential from synergistic effect of quercetin and paclitaxel co-encapsulated in the targeted folic-gelatin-pluronic P123 nanogels for chemotherapy.

Dual-drug delivery systems for anticancer therapy have recently attracted substantial attention due to their potency to overcome limitations of conventional anti-cancer drugs, tackle drug resistance problems, as well as improve the therapeutic efficacy. In this study, we introduced a novel nanogel based on folic acid-gelatin-pluronic P123 (FA-GP-P123) conjugate to simultaneously deliver quercetin (QU) and paclitaxel (PTX) to the targeted tumor. The results indicated that the drug loading capacity of FA-GP-P123 nanogels was significantly higher than that of P123 micelles. The kinetic release profiles of QU and PTX from the nanocarriers were governed by Fickian diffusion and swelling behavior, respectively. Notably, FA-GP-P123/QU/PTX dual-drug delivery system induced higher toxicity to MCF-7 and Hela cancer cells than either QU or PTX individual delivery system, and the non-targeted dug delivery system (GP-P123/QU/PTX), indicating the synergistic combination of dual drugs and FA positive targeting effect. Furthermore, FA-GP-P123 could effectively deliver QU and PTX to tumors in vivo after administration into MCF-7 tumor-bearing mice, which resulted in 94.20 ± 5.90 % of tumor volume reduced at day 14. Moreover, the side effects of the dual-drug delivery system were significantly reduced. Overall, we suggest FA-GP-P123 as potential nanocarrier for dual-drug delivery for targeted chemotherapy.

Dual Interactions of Amphiphilic Gelatin Copolymer and Nanocurcumin Improving the Delivery Efficiency of the Nanogels.

Herein, a new process to manufacture multicore micelles nanoparticles reinforced with co-assembly via hydrophobic interaction and electrostatic interaction under the help of ultrasonication was developed. The precise co-assembly between negative/hydrophobic drug and positive charged amphiphilic copolymer based pluronic platform allows the formation of complex micelles structures as the multicore motif with predefined functions. In this study, curcumin was selected as a drug model while positively charged copolymer was based on a pluronic-conjugated gelatin with different hydrophobicity length of Pluronic F87 and Pluronic F127. Under impact of dual hydrophobic and electrostatic interactions, the nCur-encapsulated core-shell micelles formed ranging from 40 nm to 70 nm and 40-100 nm by transmission electron microscopy (TEM) and Dynamic Light Scattering (DLS), respectively. It is found that the structures emerged depended on the relative lengths of the hydrophobic blocks in pluronic. Regarding g2(τ) behavior from DLS measurement, the nanogels showed a high stability in spherical form. Surprisingly, the release profiles showed a sustainable behavior of Cur from this system for drug delivery approaches. In vitro study exhibited that nCur-encapsulated complex micelles increased inhibitory activity against cancer cells growth with IC50 is 4.02 ± 0.11 mg/L (10.92 ± 0.3 µM) which is higher than of free curcumin at 9.40 ± 0.17 mg/L (25.54 ± 0.18 µM). The results obtained can provide the new method to generate the hierarchical assembly of copolymers with incorporated loading with the same property.