Paclitaxel-betulinic acid hybrid nanosuspensions for enhanced anti-breast cancer activity.

Abstract

Paclitaxel-betulinic acid hybrid nanosuspensions (PTX-BA-NP) with increased anti-breast cancer activity were developed. The resultant nanosuspensions (NP) had a mean particle size of 282.54 ± 5.4 nm, a polydispersity index of approximately 0.242 ± 0.02, a zeta potential of -19.7 ± 0.19 mV and a redispersibility index of 103.3 ± 0.01%. The cumulative dissolution percentage of PTX coarse powder and PTX-BA-NP dried powder at 60 min were 15.4% and 90.8%, respectively. MCF-7 cell-based testing showed that treatment with PTX-BA-NP led to more PTX-BA-NP accumulation in the cytoplasm of breast cancer cells, less cell cycle arrest in the G2-M phase, more cell cycle arrest in the G0-G1 phase, more apoptosis-induced cell death and stronger inhibition of cell migration than paclitaxel nanosuspensions (PTX-NP). Biodistribution studies showed that tumor accumulation levels at 12 h in the PTX-BA-NP group were approximately 2.67- and 2.33-fold higher than the levels in the Taxol® and PTX-NP groups, respectively. In vivo antitumor efficacy demonstrated that PTX-BA-NP exerted the strongest tumor inhibition among the four groups, with a tumor inhibition rate of 47.79 ± 2.28%, followed by PTX-NP (35.05 ± 5.55%), Taxol® (22.67 ± 6.01%) and betulinic acid nanosuspension (BANP) (14.38 ± 6.02%). These findings indicate that PTX-BA-NP holds great promise for breast cancer therapy.

• Authors: Ruoning Wang, Mengmeng Yang, Guoyuan Li, Xin Wang, Zhenhai Zhang, Hongzhi Qiao, Jun Chen, Zhipeng Chen, Xiaobin Cui, Junsong Li
• Journal: Colloids and surfaces. B, Biointerfaces (Colloids Surf B Biointerfaces) Vol. 174 Pg. 270-279 (Feb 01 2019) ISSN: 1873-4367 [Electronic] Netherlands
• PMID: 30469048 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Pentacyclic Triterpenes
• Triterpenes
• Paclitaxel
• Betulinic Acid

Topics

• Animals
• Antineoplastic Agents, Phytogenic (chemistry, pharmacology)
• Apoptosis (drug effects)
• Breast Neoplasms (drug therapy, pathology)
• Cell Cycle (drug effects)
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Female
• Humans
• MCF-7 Cells
• Mammary Neoplasms, Experimental (drug therapy, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Nanoparticles (chemistry)
• Paclitaxel (chemistry, pharmacology)
• Pentacyclic Triterpenes
• Structure-Activity Relationship
• Tissue Distribution
• Triterpenes (chemistry, pharmacology)
• Betulinic Acid