Dextran-poly lactide-co-glycolide polymersomes decorated with folate-antennae for targeted delivery of docetaxel to breast adenocarcinima in vitro and in vivo.

In this study, a tumor-targeted, docetaxel encapsulated dextran-poly lactide-co-glycolide (DEX-PLGA) polymersomes was fabricated for breast cancer chemotherapy. To attain active cancer targeting, docetaxel encapsulated polymersomes was conjugated with folate for folate receptor guided delivery which is overexpressed in various cancer cells including breast adenocarcinoma. Docetaxel was encapsulated in the bilayer of DEX-PLGA or folate-conjugated DEX-PLGA (FA-DEX-PLGA) polymersomes via nanoprecipitation method in order to provide the controlled drug release. The size of polymersomes obtained were 178.53±2.5nm and offered drug encapsulation efficiency and loading content of 78.85±3.81% and 9.32±0.27, respectively. The data demonstrate that the prepared polymersome formulations sustained docetaxel release for a period of 6days. Cellular uptake study and MTT assay showed that the developed folate-targeted docetaxel-loaded polymersomes had higher cytotoxicity than non-targeted ones as well as free form of drug and was accumulated in 4T1 and MCF-7 cells in vitro. The in vivo tumor inhibitory effect of folate-conjugated docetaxel-loaded DEX-PLGA polymersomes (FA-DEX-PLGA-DTX-NPs) demonstrated an increased therapeutic potency of targeted formulation over both non-targeted (DEX-PLGA-DTX-NPs) and free drug. The represented data reveal that the prepared targeted drug delivery system was able to control the docetaxel release, and also enhance the antitumor potency of docetaxel. This study may open new direction for preparation of folate receptor targeted polymersomes based on DEX-PLGA copolymers for translational purposes.

Alibolandi M ，Abnous K ，Hadizadeh F ，Taghdisi SM ，Alabdollah F ，Mohammadi M ，Nassirli H ，Ramezani M ... -  《-》

Folate receptor-targeted multimodal polymersomes for delivery of quantum dots and doxorubicin to breast adenocarcinoma: In vitro and in vivo evaluation.

In this study, we report the design and delivery of tumor-targeted, quantum dot (QD) and doxorubicin (DOX)-encapsulated PEG-PLGA nanopolymersomes (NPs) for the imaging and chemotherapy of breast cancer. To achieve active cancer targeting, QD and DOX-encapsulated NPs were conjugated with folate for folate-binding protein receptor-guided delivery, which overexpressed in many cancer cells. Hydrophobic DOX and hydrophilic MSA-capped QD were encapsulated in the bilayer and core of the PEG-PLGA nanopolymersomes, respectively. The data show that the formulated NPs sustained DOX release for a period of 12 days. Fluorescence microscopy and MTT assay demonstrated that the developed folate-targeted DOX-QD NPs had higher cytotoxicity than non-targeted NPs and the free form of the drug; moreover, they preferentially accumulated in 4T1 and MCF-7 cells in vitro. In vivo experiments including whole organ tissue-homogenate analysis and organ fluorescence microscopy imaging of BALB/c mice bearing 4T1 breast adenocarcinoma showed that the folate receptor-targeted QD encapsulated NPs accumulate at tumor sites 6h following intravenous injection. Acute toxicity studies of the prepared targeted QD-loaded NPs showed no evidence of long-term harmful histopathological and physiological effects on the treated animals. The in vivo tumor inhibitory effect of folic acid (FA)-QD-DOX NPs demonstrated an augmented therapeutic efficacy of targeted formulation over the non-targeted and free drug. The data obtained illustrate a high potential of the prepared targeted theranostic nanoplatform in the treatment and imaging of breast cancer. This study may open new directions for preparation of QD-based theranostic polymersomes for clinical application.

Alibolandi M ，Abnous K ，Sadeghi F ，Hosseinkhani H ，Ramezani M ，Hadizadeh F ... -  《-》

Docetaxel-loaded PLGA and PLGA-PEG nanoparticles for intravenous application: pharmacokinetics and biodistribution profile.

Rafiei P ，Haddadi A 《International Journal of Nanomedicine》

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 ... -  《-》

Targeted poly (L-γ-glutamyl glutamine) nanoparticles of docetaxel against folate over-expressed breast cancer cells.

A novel folate (FA) conjugated poly(l-γ-glutamyl glutamine) (PGG) nanoparticle loaded with docetaxel (DTX) was prepared to take advantage of both targeted drug delivery in breast cancer and reducing the overall side effects due to the adjuvant free formulation in comparison with Taxotere(®). Nanoprecipitation method was employed to prepare nanoparticles (NPs). The chemical structure of PGG synthesized polymers and PGG-FA conjugates and polymeric nanoparticles were characterized by H NMR, FTIR spectroscopy, field emission scanning electron microscopy, and laser scanning confocal microscopy. The average size of optimized nanoparticles with the aid of Box-Behnken experimental design was 131.96 ± 5.34(nm) with polydispersity of 0.089 ± 0.019, zeta potential of -25.8 ± 2.21(mV), and entrapment efficiency of 67.83 ± 3.29(%). In vitro cytotoxicity of the designed NPs was investigated by MTT assay against three chosen cell lines of MCF7, 4T1, and A549 based on their folate receptor expression capacity and was compared with Taxotere(®). Moreover, PGG-FOL NPs were loaded with 6-coumarin for cellular uptake investigation. In order to assess the antitumor efficacy and biodistribution of targeted NPs, 4T1 murine breast tumors were established on the balb/c mice and in vivo studies were performed. The obtained results showed that the novel designed system was highly effective against tumor cells and successfully localized in the tumor site.

Tavassolian F ，Kamalinia G ，Rouhani H ，Amini M ，Ostad SN ，Khoshayand MR ，Atyabi F ，Tehrani MR ，Dinarvand R ... -  《-》