Physicochemical characterization, in vitro and in vivo evaluation of chitosan/carrageenan encumbered with Imatinib mesylate-polysarcosine nanoparticles for sustained drug release and enhanced colorectal cancer targeted therapy

Sankha Bhattacharya; Smita Bonde; Ketan Hatware; Satyam Sharma; Md Meraj Anjum; Ram Kumar Sahu

doi:10.1016/j.ijbiomac.2023.125529

Physicochemical characterization, in vitro and in vivo evaluation of chitosan/carrageenan encumbered with Imatinib mesylate-polysarcosine nanoparticles for sustained drug release and enhanced colorectal cancer targeted therapy

Int J Biol Macromol. 2023 Aug 1:245:125529. doi: 10.1016/j.ijbiomac.2023.125529. Epub 2023 Jun 26.

Authors

Sankha Bhattacharya¹, Smita Bonde², Ketan Hatware², Satyam Sharma³, Md Meraj Anjum⁴, Ram Kumar Sahu⁵

Affiliations

¹ School of Pharmacy & Technology Management, SVKM'S NMIMS Deemed-to-be University, Shirpur, Maharashtra 425405, India. Electronic address: sankhabhatt@gmail.com.
² School of Pharmacy & Technology Management, SVKM'S NMIMS Deemed-to-be University, Shirpur, Maharashtra 425405, India.
³ Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Export Promotion Industrial Park (EPIP), Zandaha Road, NH322, Hajipur, Bihar 844102, India.
⁴ Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, India.
⁵ Department of Pharmaceutical Sciences, HNB Garhwal University (A Central University), Chauras Campus, P.O. Kilkileshwar, Via Kritinagar, Distt. Tehri Garhwal Pin-249161, Uttarakhand, India.

PMID: 37379942
DOI: 10.1016/j.ijbiomac.2023.125529

Abstract

The objective of this investigation was to fabricate nanoparticles consisting of Imatinib mesylate-poly sarcosine-loaded chitosan/carrageenan in order to attain prolonged drug release and efficacious therapy for colorectal cancer. The study involved the synthesis of nanoparticles through the utilisation of ionic complexation and nanoprecipitation techniques. The subsequent nanoparticles were subjected to an assessment of their physicochemical characteristics, anti-cancer efficacy using HCT116 cell line, and acute toxicity. The present study examined two distinct nanoparticle formulations, namely IMT-PSar-NPs and CS-CRG-IMT-NPs, with respect to their particle size, zeta potential, and morphology. Both formulations demonstrated satisfactory characteristics, as they displayed consistent and prolonged drug release for a duration of 24 h, with the highest level of release occurring at a pH of 5.5. The efficacy and safety of IMT-PSar-NPs and CS-CRG-IMT-PSar-NPs nanoparticles were evaluated through various tests including in vitro cytotoxicity, cellular uptake, apoptosis, scratch test, cell cycle analysis, MMP & ROS estimate, acute toxicity, and stability tests. The results suggest that these nanoparticles were well fabricated and have promising potential for in vivo applications. The prepared polysaccharide nanoparticles have great potential for active targeting and could potentially reduce dose-dependent toxicity in the treatment of colon cancer.

Keywords: Carrageenan; Chitosan; Colon cancer.