Pharmacokinetics and in vitro/in vivo antitumor efficacy of aptamer-targeted Ecoflex^® nanoparticles for docetaxel delivery in ovarian cancer

Abstract

Purpose Epithelixal ovarian cancer is the fourth cause of cancer death in developed countries with 77% of ovarian cancer cases diagnosed with regional or distant metastasis, with poor survival rates. Docetaxel (DTX) is a well-known anticancer agent, with clinically proven efficacy in several malignancies, including ovarian cancer. However, the adverse effects caused by the active ingredient or currently marketed formulations could even deprive the patient of the advantages of treatment. Therefore, in the current study, polymeric nanoparticles (NPs) equipped with aptamer molecules as targeting agents were proposed to minimize the adverse effects and enhance the antitumor efficacy through directing the drug cargo toward its site of action. Materials and methods Electrospraying technique was implemented to fabricate poly (butylene adipate-co-butylene terephthalate) (Ecoflex ® ) NPs loaded with DTX (DTX-NPs). Afterward, aptamer molecules were added to the DTX-NPs, which bound via covalent bonds (Apt-DTX-NPs). The particle size, size distribution, zeta potential, entrapment efficiency, and release profile of the NPs were characterized. Using MTT assay and flow-cytometry analysis, the in vitro cytotoxicity and cellular uptake of the NPs were compared to those of the free drug. Following intravenous administration of Taxotere ® , DTX-NPs, and Apt-DTX-NPs (at an equivalent dose of 5 mg/kg of DTX), pharmacokinetic parameters and antitumor efficacy were compared in female Balb/c and HER-2-overexpressing tumor-bearing B6 athymic mice, respectively. Results The obtained results demonstrated significantly enhanced in vitro cytotoxicity and cellular uptake of Apt-DTX-NPs in a HER-2-overexpressing cell line, comparing to DTX-NPs and the free drug. The results of in vivo studies indicated significant increment in pharmacokinetic parameters including the area under the plasma concentration–time curve, mean residence time, and elimination half-life. Significant increment in antitumor efficacy was also observed, probably due to the targeted delivery of DTX to the tumor site and enhanced cellular uptake as evaluated in the aforementioned tests. Conclusion Hence, the proposed drug delivery system could be considered as an appropriate potential substitute for currently marketed DTX formulations.

HER‐2 aptamer‐targeted Ecoflex ® nanoparticles loaded with docetaxel promote breast cancer cells apoptosis and anti‐metastatic effect

“…DTX‐loaded NPs were prepared and attached to HER‐2‐specific aptamer according to the method reported by Ghassami et al [17]. Briefly, 1:3 mixture of DTX and polymer was dissolved in a 2.7:1 mixture of dichloromethane and N,N‐dimethyl formamide.…”

Atrial natriuretic peptide modified oleate adenosine prodrug lipid nanocarriers for the treatment of myocardial infarction: in vitro and in vivo evaluation

“…In vitro release of Ade from the LNCs was studied by dialysis method in a pH 7.4 medium containing 10% FBS. 26 Briefly, suspensions of Ade/LNCs and ANP Ade/LNCs were placed inside a dialysis bag (cutoff 12,000 Da) and stirred at 37°C for 72 h. At predetermined time points, 100 μL samples were withdrawn and replaced with fresh medium intervals. The Ade concentration in samples was analyzed by the same method mentioned in the “Preparation and characterization of LNCs” section.…”

Stimuli‐responsive nanotherapeutics for precision drug delivery and cancer therapy

“…Aptamers are highly resistant to blood and tissue nucleases, owing to their 2' modified sugars, while their ‐NH2 at 3' terminus can be modified for coupling to other molecules such as PEG (Pangburn TO et al, ). For example, DTX‐loading poly (butylene adipate‐co‐butylene terephthalate) NPs decorated with Aptamers against HER2 (Ap‐NPs) exhibited significantly enhanced in vitro cytotoxicity and cellular uptake, as well as in vivo antitumor efficacy in a HER‐2‐overexpressing ovarian cancer cell line, as compared with undecorated NPs and the free drug (Ghassami et al, ).…”