Novel docetaxel chitosan-coated PLGA/PCL nanoparticles with magnified cytotoxicity and bioavailability.

In the present study, docetaxel (DTX)-loaded poly(lactic-co-glycolic acid) (PLGA) and polycaprolactone (PCL) nanoparticles were successfully prepared and coated with chitosan (CS). The prepared nanoparticles (NPs) were evaluated for their particle size, zeta potential, particle morphology, drug entrapment efficiency (EE%), and in vitro drug release profile. The anticancer activity of DTX-loaded NPs was assessed in human HT29 colon cancer cell line utilizing MTT assay. The pharmacokinetics of DTX-loaded NPs was monitored in Wistar rats in comparison to DTX solution. The prepared NPs exhibited particle sizes in the range 177.1 ± 8.2-287.6 ± 14.3 nm. CS decorated NPs exhibited a significant increase in particle size and a switch of zeta potential from negative to positive. In addition, high EE% values were obtained for CS coated PCL NPs and PLGA NPs as 67.1 and 76.2%, respectively. Moreover, lowering the rate of DTX in vitro release was achieved within 48 h by using CS coated NPs. Furthermore, a tremendous increase in DTX cytotoxicity was observed by CS-decorated PLGA NPs compared to all other NPs including DTX-free-NPs and pure DTX. The in vivo study revealed significant enhancement in DTX bioavailability from CS-decorated PLGA NPs with more than 4-fold increase in AUC compared to DTX solution. In conclusion, CS-decorated PLGA NPs are a considerable DTX-delivery carrier with magnificent antitumor efficacy.

Badran MM ，Alomrani AH ，Harisa GI ，Ashour AE ，Kumar A ，Yassin AE ... -  《-》

Preparation and characterization of surface-modified PLGA-polymeric nanoparticles used to target treatment of intestinal cancer.

Ahmad N ，Alam MA ，Ahmad R ，Naqvi AA ，Ahmad FJ ... -  《-》

Hyaluronic acid-decorated poly(lactic-co-glycolic acid) nanoparticles for combined delivery of docetaxel and tanespimycin.

Multiple-drug combination therapy is becoming more common in the treatment of advanced cancers because this approach can decrease side effects and delay or prevent drug resistance. In the present study, we developed hyaluronic acid (HA)-decorated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (HA-PLGA NPs) for co-delivery of docetaxel (DTX) and tanespimycin (17-AAG). DTX and 17-AAG were simultaneously loaded into HA-PLGA NPs using an oil-in-water emulsification/solvent evaporation method. Several formulations were tested. HA-PLGA NPs loaded with DTX and 17-AAG at a molar ratio of 2:1 produced the smallest particle size (173.3±2.2nm), polydispersity index (0.151±0.026), and zeta potential (-12.4±0.4mV). Approximately 60% and 40% of DTX and 17-AAG, respectively, were released over 168h in vitro. Cytotoxicity assays performed in vitro using MCF-7, MDA-MB-231, and SCC-7 cells showed that dual drug-loaded HA-PLGA NPs at a DTX:17-AAG molar ratio of 2:1 exhibited the highest synergistic effect, with combination index values of 0.051, 0.036, and 0.032, respectively, at the median effective dose. Furthermore, synergistic antitumor activity was demonstrated in vivo in a CD44 and RHAMM (CD168) - overexpressing squamous cell carcinoma (SCC-7) xenograft in nude mice. These findings indicated that nanosystem-based co-delivery of DTX and 17-AAG could provide a promising combined therapeutic strategy for enhanced antitumor therapy.

Pradhan R ，Ramasamy T ，Choi JY ，Kim JH ，Poudel BK ，Tak JW ，Nukolova N ，Choi HG ，Yong CS ，Kim JO ... -  《-》

Preparation and characterization of polymeric nanoparticles surface modified with chitosan for target treatment of colorectal cancer.

5-Fluorouracil (5-FU) loaded chitosan (C) coated polylactic-co-glycolic acid (PLGA) nanoparticles [NPs] (C-5-FU PLGA NPs) and polycaprolactone [PCL] (C-5-FU PCL NPs) were employed as the carriers for cancer treatment. The prepared NPs showed the spherical shape of NPs with the particle size in the range of 188.1-302.2nm with polydispersity index (PDI) of <0.30. C-coated NPs converted zeta potential from negative to positive value with small modification in particle size distribution. The entrapment efficiency of 5-FU was recorded in the range of 32-51%. The in vitro release studies showed an initial rapid 5-FU release followed by a sustained release profile. The in vitro cytotoxicity of C-5-FU PLGA NPs showed significant inhibition of colon cancer cells (HT-29) compared to the other NPs and drug solution. These results showed that C-5-FU PLGA NPs can be considered as a promising carrier for cancer therapy.

Badran MM ，Mady MM ，Ghannam MM ，Shakeel F ... -  《-》

The tumor-targeting core-shell structured DTX-loaded PLGA@Au nanoparticles for chemo-photothermal therapy and X-ray imaging.

In this study, an organic-inorganic hybrid nanocomposite was synthesized by deposition of Au onto the surface of docetaxel (DTX)-loaded poly (lactide-co-glycolide) (PLGA) nanoparticle cores to form the core-shell structured DTX-loaded PLGA@Au nanoparticles. The tumor targeting peptide, angiopep-2, was then introduced onto the gold nanoshell through Au-S bond, achieving drug delivery with active targeting capability. This novel system allowed combined chemotherapy and thermal therapy for cancer, resulting from DTX and gold nanoshell. The formation of tumor-targeting gold nanoshell surrounding PLGA nanocore, designated as ANG/GS/PLGA/DTX NPs, was confirmed by its surface plasmon resonance (SPR) band in the UV-Vis spectrum and by a transmission electron microscope (TEM). The release profiles of DTX from this system showed strong dependence on near-infrared (NIR) laser. Compared with DTX alone, the ANG/GS/PLGA/DTX NPs afforded much higher anti-tumor efficiency without obvious toxic effects. Besides, it also showed potential X-ray imaging ability. These results demonstrated that the tumor-targeting core-shell structured DTX-loaded PLGA@Au nanoparticles could be used as a multifunctional nanomaterial system with NIR-triggered drug-releasing properties for tumor-targeted chemo-photothermal therapy and theranostics.

Hao Y ，Zhang B ，Zheng C ，Ji R ，Ren X ，Guo F ，Sun S ，Shi J ，Zhang H ，Zhang Z ，Wang L ，Zhang Y ... -  《-》