The Dual Modification of PNIPAM and β-Cyclodextrin Grafted on Hyaluronic Acid as Self-Assembled Nanogel for Curcumin Delivery

Abstract

Curcumin is an extract of turmeric (Curcuma longa) which possesses anti-inflammatory, anti-cancer and wound-healing effects and has been used as an active compound in biomedical research for many years. However, its poor solubility presents challenges for its use in drug delivery systems. A modified nanogel delivery system, with PNIPAM and β-cyclodextrin grafted onto hyaluronic acid (PNCDHA), was utilized to enhance the solubility. The polymer was characterized by NMR, and the inclusion complex between curcumin and β-cyclodextrin was confirmed by FTIR. The potential of this PNCDHA polymer complex as a drug delivery vehicle was supported by a curcumin encapsulation efficiency of 93.14 ± 5.6% and the release of encapsulated curcumin at 37 °C. At a concentration of 0.5% w/v in water, PNCDHA nanogels were biocompatible with fibroblast cell line (L929) up to a curcumin concentration of 50 µM. There was a direct concentration between curcumin loading and cellular internalization. A more detailed study of the cellular internalization of PNCDHA nanogel should be considered in order to clarify cellular delivery mechanisms and to assess how its viability as a carrier may be optimized.

Synthesis of a smart pH sensitive micelle containing hyaluronic acid-curcumin bioconjugate against colorectal cancer

“…7A). Various studies have demonstrated the role of HA as a targeting moiety for guided delivery of anticancer nanomedicines [24,38,39]. In this regard, Lai et al, indicated that the pH-responsive acidlabile hydrazine linkage of HA-CUR conjugate can noticeably improve the antitumor e cacy of murine metastatic breast cancer in vitro and in vivo [10].…”

Hyaluronic Acid Nanogels: A Promising Platform for Therapeutic and Theranostic Applications

“…Temperature-sensitive HA nanogels can be obtained by grafting thermoresponsive polymers onto the HA chains, such as di(ethylene glycol)methacrylate (DEGMA)-based polymers [ 44 , 90 ], or pNIPAM [ 49 ]. These polymers are hydrophobic relative to HA, resulting in self-assembly into nanogel structures driven by hydrophobic interactions.…”

“…The self-assembly of amphipathic HA into nanogels is driven by hydrophobic interactions, resulting in polymeric micelles in water. A variety of hydrophobic molecules have been trialed for this purpose, including linear alkyl chains [28][29][30][31][32][33][34], bulky hydrophobic molecules (e.g., cholesterol [35][36][37], pyrene [38,39], cholanic acid [40][41][42], and indocyanine green [43]), and hydrophobic polymers (e.g., ethylene glycol [44,45], polycaprolactone or PCL [46,47], poly(lactic-co-glycolic acid) or PLGA [48], and poly(N-isopropylacrylamide) or pNIPAM [49]. Additionally, HA can be covalently conjugated with metal-chelating functional groups, such as histidine amino acids and chelating agents such as iminodiacetic acid and malonic acid.…”

“…The template is then removed after the crosslinking reaction [53]. Cholesterol [35][36][37] Pyrene [38,39] Cholanic acid [40][41][42] Indocyanine green [43] Ethylene glycol [44,45] Polycaprolactone (PCL) [46,47] Poly(lactic-co-glycolic acid) (PLGA) [48] Poly(N-isopropylacrylamide) (pNIPAM) [1,49,79,80] Chemical crosslinking Amide bond formation with amine linkers using carbodiimide reaction (+) Robust nanogel structure (−) Difficult to control morphology and size of the particles (−) Extra steps to remove excess crosslinkers [5,[52][53][54] Crosslinking of amine-conjugated HA using aldehyde crosslinkers [55,56] Specific crosslinkers for HA [57,58] Self-crosslinking Disulfide formation (+) Simple fabrication (+) Redox-responsiveness (for disulfide-formed HA nanogels) [31,[59][60][61][62][63][64][65] Self-crosslinking of methacrylated HA [66][67][68][69][70] Photocrosslinking of methacrylated HA or tetrazole-modified HA 73-77 [73][74][75]…”

β-Cyclodextrin and Hyaluronic Acid-Modified Targeted Nanodelivery System for Atherosclerosis Prevention

“…19 A recent study showed that an improved nanogel delivery system with poly(N-isopropylacrylamide) and β-CD grafted onto HA could improve the solubility of curcumin and promote its release under physiological conditions. 20 Therefore, it can be predicted that the synergy of various functionalized CDs will improve the stability of drugs while accurately delivering them to the lesion site. 21 In this work, we used the weak acidic microenvironment and accumulated macrophages in atherosclerotic lesions to design a dual-carrier nanodrug-loading platform for low pH response and CD44 receptor targeting (Scheme 1 and Figure S1).…”