Hybrid Nanoparticle for Co-delivering Paclitaxel and Dihydroartemisinin to Exhibit Synergic Anticancer Therapeutics

Bao Ngoc Tran; Thu Thi Kim Ninh; Thao Thi Do; Phuong Thi Do; Chien Ngoc Nguyen

doi:10.2174/0115680096283208231229103822

Hybrid Nanoparticle for Co-delivering Paclitaxel and Dihydroartemisinin to Exhibit Synergic Anticancer Therapeutics

Curr Cancer Drug Targets. 2024 Feb 6. doi: 10.2174/0115680096283208231229103822. Online ahead of print.

Authors

Bao Ngoc Tran¹, Thu Thi Kim Ninh², Thao Thi Do³, Phuong Thi Do³, Chien Ngoc Nguyen^{1

4}

Affiliations

¹ Department of Pharmaceutical Industry, Faculty of Pharmaceutical Technology, Hanoi University of Pharmacy, Hanoi, Vietnam.
² Faculty of Pharmacy, HaiPhong University of Medicine and Pharmacy, Hai-Phong, Vietnam.
³ Institute of Biotechnology, Vietnam Academy of Science and Technology, Hanoi, Vietnam.
⁴ National Institute of Pharmaceutical Technology, Hanoi University of Pharmacy, Hanoi, Vietnam.

PMID: 38321897
DOI: 10.2174/0115680096283208231229103822

Abstract

Aim: Anticancer treatment is required to provide effective and safe patient medicines. This research aided in developing and applying nanoparticles (NPs) for cancer treatment.

Background: The poor solubility of paclitaxel (PTX) restricts its therapeutic efficacy because of allergic side effects caused by formulation excipients. To overcome this, PTX was coupled with artemisinin derivatives and loaded into an NP drug delivery system to enhance its effects while addressing its low solubility.

Objectives: This study prepared and characterized a hybrid PLGA-lecithin NP containing dihydroartemisinin (DHA) and PTX for synergic anticancer therapy. A lyophilization study improved the stability of the NP drug formulations.

Methods: Dual PTX- and DHA-loaded PLGA- and lecithin-based NPs were prepared using a single-step solvent evaporation method. The NP suspensions were lyophilized, and the types and ratios of cryoprotectants were investigated. The physicochemical properties of NPs and lyophilized cakes (Lyo-NPs) were characterized. The stability of the Lyo-NPs was investigated at 2-8°C and room conditions. The anticancer effects of the drug combination, NP suspension, and lyophilized powder were analyzed using an in vitro cytotoxicity assay and an in vivo model.

Results: The optimal PTX-DHA loaded PLGA-lecithin-NP was formulated (200 nm, PDI: 0.248 ± 0.003, Zeta potential: -33.60 ± 3.39 mV). Mannitol was selected for lyophilization. Lyo-NPs improved the stability of the NPs (1 year), wherein the physicochemical properties of the NPs were maintained (RDI was close to 1.0). An in-vitro cytotoxicity assay of PTX combined with DHA showed a synergistic anticancer effect (CI <1.0). The suppressive effects of Lyo-NPs on tumor growth in vivo were dose-dependent. While the cocktail of free drugs showed high toxicity (7.5 mg PTX-15 mg DHA/kg) in-vivo, Lyo-NPs showed no statistical differences in hematological and biochemical parameters compared to the control.

Conclusion: Dual-drug-loaded hybrid PLGA-lecithin NP is a potential system to minimize severe side effects while enhancing antitumor efficacy, in which lyophilization is a key process to increase stability.</p>.

Keywords: Paclitaxel; anticancer therapy; artemisinin derivatives.; hybrid nanoparticle; lyophilization; stability; synergic therapy.