Green synthesis of hyaluronic acid coated, thiolated chitosan nanoparticles for CD44 targeted delivery and sustained release of Cisplatin in cervical carcinoma

Abstract

Cervical carcinoma is one of the most prevalent gynecological cancers throughout the world. Cisplatin is used as first line chemotherapy for treatment of cervical cancer, but it comes with plethora of side effects. The aim of this study was to develop hyaluronic acid coated, thiolated chitosan nanocarriers using green synthesis approach, for CD44 targeted delivery and sustained release of Cisplatin in cervical cancer cells. After synthesis through ionic gelation method, Zeta analysis showed that the nanoparticle size was 265.9 nm with a zeta potential of +22.3 mV and .226 PDI. SEM and TEM analysis confirmed the spherical shape and smooth surface of nanoparticles. FTIR and XRD showed the presence of characteristic functional groups, successful encapsulation of drug, and crystalline nature of nanoparticles respectively. Drug loading and entrapment efficiency were calculated to be 70.1% ± 1.2% and 45% ± .28% respectively. Analysis of in vitro drug release kinetics showed that drug release followed the Higuchi model at pH 6.8 and 7.4 and Cisplatin release for up to 72 h confirmed sustained release. In vitro analysis on cervical cancer cells HeLa and normal cervical epithelial cells HCK1T was done through cell morphology analysis, trypan blue assay (concentration range of 10–80 μg/ml), and MTT cytotoxic assay (concentration range of 10–90 μg/ml). The results showed a higher cytotoxic potential of HA coated, thiolated chitosan encapsulated Cisplatin (HA-ThCs-Cis NP) nanoformulation as compared to pure Cisplatin in HeLa while in HCK1T, pure Cisplatin showed much higher toxicity as compared to HA-ThCs-Cis nanoformulation. These findings suggest that CD44 targeted delivery system can be a useful approach to minimize offtarget toxicities, give sustained release and better cellular uptake in cancer cells.

Enhancing therapeutic efficacy: sustained delivery of 5-fluorouracil (5-FU) via thiolated chitosan nanoparticles targeting CD44 in triple-negative breast cancer

“…Its functional reactive sites make it ideal for therapeutic applications, and it binds to CD44 receptors, which are overexpressed in solid tumors. This receptor-specific binding allows hyaluronic acid to be utilized in drug delivery systems, targeting tumor cells while minimizing its penetration into normal tissues 24 .…”

“…This study used 5-FU, a potent anticancer therapeutic moiety, to formulate a drug delivery system (DDS) using HA-coated TCs. The primary objective was to target tumor sites by binding to CD44 receptors and releasing therapeutic moiety through receptor-mediated endocytosis at the specific cells 23 , 24 Fig. 1 .…”

CD44 targeted delivery of oncolytic Newcastle disease virus encapsulated in thiolated chitosan for sustained release in cervical cancer: a targeted immunotherapy approach

“…In cancer therapy, thiolated chitosan (ThCs) have several favorable characteristics such as flexibility of surface functionalization with various targeting moieties, pH sensitive swelling behavior and controlled release of loaded therapeutic moiety. Furthermore, enhanced absorptive endocytosis of the drug/virus loaded thiolated chitosan nanocarriers occur due to formation of disulphide bonds with exofacial thiol groups of the transmembrane proteins ( 9 , 10 ). To achieve active targeting, thiolated chitosan based drug delivery system can be surface functionalized with specific ligands (folic acid, hyaluronic acid) that can bind with specific receptors (folate receptor, CD44 receptor) on cancer cells.…”

Anticancer analysis of CD44 targeted Cyclosporine loaded thiolated chitosan nanoformulations for sustained release in triple-negative breast cancer

“…These attributes substantially improve the pharmacokinetic characteristics, effectiveness, and targeted delivery of N.F.s as a possible localized therapeutic constituent in cancer therapy. Moreover, in-vivo testing of these formulations is required in considering these results [9,12].…”

“…Physiological linkages with anionic substances found in the strands of other polysaccharides result in the production of covalent or ionic interactions, increasing Cs' magnetic strength [11]. The procedure, renowned as the "Ionic Gelation technique," depends on the electrostatic interactions in the presence of contrarily charged groups [12]. The benefits of this technology include the convenience of handling, the inclusion of biocompatible natural ingredients, and the uncomplicated regulation of particle size.…”