Effects of the Molecular Weight of Hyaluronic Acid in a Carbon Nanotube Drug Delivery Conjugate

Abstract

Hyaluronic acid (HA) is a ubiquitous biopolymer involved in many pathophysiological roles. One HA receptor, the cluster of differentiation CD44 protein, is often overexpressed in tumor cells. As such, HA has attracted considerable interest in the development of drug delivery formulations, given its intrinsic targetability toward CD44 overexpressing cells. The present study is focused on examining the correlation of HA molecular weight with its targetability properties. A library of conjugates obtained by linking the amino group of the phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE) to the carboxylic residues of HA of different molecular weight (6.4, 17, 51, 200, and 1,500 kDa) were synthesized and fully characterized. The HA-DMPE conjugates were then used to non-covalently functionalize the highly hydrophobic single-walled carbon nanotubes (CNT), and further encapsulate the anticancer drug doxorubicin (DOX). Our results show that the complexes DOX/CNT/HA-DMPE maintain very good and stable dispersibility. Drug release studies indicated a pH-responsive release of the drug from the nanocarrier. Cell viability tests demonstrated that all HA modified CNTs have good biocompatibility, and specific targeting toward cells overexpressing the CD44 receptor. Among all the molecular weights tested, the 200 kDa HA showed the highest increase in cellular uptake and cytotoxic activity. All these promising attributes make CNT/HA200-DMPE a “smart” platform for tumor-targeted delivery of anticancer agents.

Liposomes Loaded with Everolimus and Coated with Hyaluronic Acid: A Promising Approach for Lung Fibrosis

“…For this reason, we decided to exploit liposomes to encapsulate drugs potentially useful for CLAD and CTD-ILD affected patients to reduce side effects increasing their efficacy only in specific cell population. In particular, we modified liposomes surface with HA, given that our target are LFs, the key elements of fibrotic lesions, and considering that increasing HA molecular weight increased its targeting efficiency for CD44, we decided to modify liposomes with a high MW HA: 400 kDa [ 20 , 23 , 24 ]. Since our final aim is to administer these nanoparticles through aerosol administration, we must also consider the presence of mucus.…”

Biocompatible Dispersants for Carbon Nanomaterials

“…In an attempt to improve the dispersion efficiency of BAS, Gubitosi et al functionalised a range of BASs with aromatic substituents at varying positions [52] (Table 3 (6)). It was postulated that adding aromatic groups to the BAS structure would increase the molecules' affinity SWCNTs by inducing π-π stacking interactions.…”

“…More recently, Arpicco et al applied this approach to SWCNTs. Through the addition of HA-DMPE and doxorubicin (DOX), they produced a DOX/SWCNT/HA-DMPE hybrid system for intelligent, targeted drug delivery [6] (Table 5 (5)). This innovative system showed excellent biocompatibility, targeting of CD44 + overexpressing cells and pH-triggered drug release.…”

“…One way around that is to utilise O 2 purging during the coating process [70] to produce a uniform, thin coating. Lee et al developed a PD/polyether amine surface coating for MWCNTs that allowed for tunable solubility by varying chain length and amine groups in the final coating [70] (Table 5 (6)).…”

“…Their impressive mechanical strength, extremely high surface area, and thermal properties have not escaped the interest of researchers [3]. With applications in engineering [4,5], biomedicine [6,7], and renewable energy [8,9], this unique class of materials, and indeed nanotechnology in general, is set to have an enormous impact on our future. In fact, nanomedicine has been recognised as a "key enabling technology" by the EU [10]; by 2016, the FDA had approved 51 nanomedicines [11].…”