Development and characterization of chitosan nanoparticles containing an indanonic tricyclic spiroisoxazoline derivative using ion-gelation method: an in vitro study

Abstract

Biodegradable nanoparticulate carriers are potentially applicable compounds in the administration of therapeutic agents and drug delivery. They have received much attention due to their biological characteristics such as biodegradability, biocompatibility, and bioadhesive. The objectives of this work are first, investigating the impact of two important parameters (i.e. chitosan or sodium tripolyphosphate (TPP) solution concentration and chitosan to TPP mass ratio) on the chitosan nanoparticles (CNPs) formation by ionic-gelation method and then, the synthesis and characterization of chitosan-based, biodegradable drug-loaded nanoparticles in the encapsulation of novel 4′-(4-(methylsulfonyl)phenyl)-3′-(3,4,5-trimethoxyphenyl)-4′H-spiro[indene-2,5′-isoxazol]-1(3H)-one (MTS) indanonic tricyclic spiroisoxazoline, which is a potent anticancer drug. The particle size, shape, zeta potential, drug loading capacity, in vitro release characteristics, and stability of the formulated drug-loaded nanoparticles of the different drug:carrier ratio has been studied. The results indicated that the particle size increased at the higher chitosan or TPP concentration while the mass ratio did not appear to be a significant parameter during the cross-linking process. The particle diameter and zeta potential of CNPs including MTS were approximately in the range of 256–350 nm and 24.08–38.70 mV, respectively. The entrapment efficiency steadily increased with increasing the concentration of the polymer in formulizations. Throughout 24 h, the in vitro release behavior was provided a sustained release from all the drug-loaded formulizations. The optimal formulization of CNPs based on drug content with a drug:carrier ratio of 1:2 did not change appreciably during 60-day storage at either 4 °C or the ambient temperature.

Keywords:

• Chitosan nanoparticles
• ionic gelation
• drug delivery
• indanonic tricyclic spiroisoxazoline
• sustained release
• polymer synthesis

Acknowledgments

The authors are grateful to Dr. Davoud Biria, Dr. Afshin Zarghi and Dr. Ali Zarrabi for critical scientific support.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The present work was financially supported by the Cellular and Molecular Research Center of Qom University of Medical Sciences (Grant Code: 97997), Shahid Beheshti University of Medical Sciences and Isfahan University.