N-octyl-N-arginine-chitosan micelles for gambogic acid intravenous delivery: characterization, cell uptake, pharmacokinetics, and biodistribution

Abstract

Objective: The deeper research of N-octyl-N-arginine chitosan (OACS) as intravenous delivery was characterized, cell uptake study, pharmacokinetics, and biodistribution of OACS micelles (GA–OACS) were investigated.

Significance: Gambogic acid (GA) can inhibit the growth of various cancer cells. However, the short elimination half-life time and treatment without targeting limits its application. OACS was synthesized as delivery carrier for GA by us, but the deeper characterization of OACS, such as molecular modeling, pharmacokinetics, and biodistribution were not investigated.

Methods: Gambogic acid loaded OACS micelles (GA–OACS) were evaluated by the molecular modeling, characterized by TEM, DLS, IR, ¹HNMR, XRD. Confocal laser scanning microscope and flow cytometry were analyzed for cell uptake study. Imaging analysis was used to show the distribution of OACS in vivo directly, pharmacokinetics and biodistribution were also investigated.

Results: The molecular modeling result showed that GA could encapsulated stably in the core of OACS micelles. TEM, IR, ¹HNMR, and XRD also suggested that GA was encapsulated in amorphous form in the core of OACS micelles. AUC and elimination half-life of GA–OACS were all increased by 1.5-fold and 2.0-fold compared with GA–ARG in rat, respectively. Biodistribution study indicated that GA–OACS was distributed mainly in the liver. GA amount in the kidney and heart was greatly reduced in the GA–OACS group. From the imaging analysis, OACS distribution in the liver was the most.

Conclusions: OACS was an excellent carrier for GA intravenous delivery to prolong half-life. Moreover, OACS targeted on liver.

Keywords:

• N-octyl-N-arginine-chitosan
• gambogic acid
• micelle
• pharmacokinetics
• biodistribution

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This work was supported by the Visiting Scholar Foundation of Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education under Grant [No. CQKLBST-2016-008]; National Natural Science Foundation of China under Grant [No. 81102817]; [China Spark Program] under Grant [No. 2015GA690276]; Yancheng City Agricultural Science and Technology Innovation Project under Grant [No. YKN2016011]; Jiangsu Provincial Key Laboratory of Coastal Wetland Bioresources under Grant [No. JKLBS2015008]; Opening project of Jiangsu Key Laboratory of Biochemistry and Biotechnology of Marine Wetland under Grant [No. K2016–12]; Jiangsu Provincial Key Project of Students? Innovation [No. 201710324015X]; Jiangsu Overseas Visiting Scholar Program for University Prominent Young & Middle-aged Teachers and Presidents; Jiangsu Provincial Qing Lan Project and Yancheng Teachers University youth talent support program.