Engineered Hyaluronic Acid-Based Smart Nanoconjugates for Enhanced Intracellular Drug Delivery

Bacterial polysaccharides can be easily modified to offer dual stimuli-responsive drug delivery systems with double targeting potential. In this research work, bacterial polysaccharides hyaluronic acid (HA) were functionalized with α-tocopherol polyethylene glycol succinate (TPGS) and cholic acid (C...

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Veröffentlicht in:Journal of pharmaceutical sciences 2023-06, Vol.112 (6), p.1603-1614
Hauptverfasser: Arjama, Mukherjee, Mehnath, Sivaraj, Rajan, Mariappan, Jeyaraj, Murugaraj
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container_end_page 1614
container_issue 6
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container_title Journal of pharmaceutical sciences
container_volume 112
creator Arjama, Mukherjee
Mehnath, Sivaraj
Rajan, Mariappan
Jeyaraj, Murugaraj
description Bacterial polysaccharides can be easily modified to offer dual stimuli-responsive drug delivery systems with double targeting potential. In this research work, bacterial polysaccharides hyaluronic acid (HA) were functionalized with α-tocopherol polyethylene glycol succinate (TPGS) and cholic acid (CA) to form multifunctional polysaccharides nanoconjugates (TPGS-HA-CA). Smart nanoconjugates were synthesized by forming a redox-responsive disulfide bond, and it is composed of double targeting ligands. Doxorubicin (DOX) encapsulated smart nanoconjugates were exhibited an average size of 200 nm with a uniform core-shell structure. It serves the pH-responsive side chain modulation of TPGS-HA-CA, which affords a high degree of swelling at acidic pH. Under the pH 5.0 it shows 57% of release due to the side chain modulation of C–H/N–H. Polysaccharides nanoconjugates exhibited the double stimuli-responsive drug delivery by rapid disassembly of disulfide linkage, which exhibited 72% drug release (pH 5.0+GSH 10 mM). In cytotoxic studies, DOX@TPGS-HA-CA exhibited a higher cytotoxic effect compared to DOX. Hyaluronic acid functionalization with CA, TPGS increases cell internalization, and dual stimuli activity promotes more cell death. Overall, multifunctional polysaccharides hydrogel nanoconjugates is a prospective material that has great potential for targeting breast cancer therapy.
doi_str_mv 10.1016/j.xphs.2021.10.005
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Hyaluronic acid functionalization with CA, TPGS increases cell internalization, and dual stimuli activity promotes more cell death. 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subjects Antineoplastic Agents - therapeutic use
Disulfides
Doxorubicin
Drug Delivery Systems
Drug Liberation
Dual-targeted delivery
Humans
Hyaluronic acid
Hyaluronic Acid - chemistry
Hydrogen-Ion Concentration
Nanoconjugates - chemistry
Smart nanoconjugates
α-tocopherol
title Engineered Hyaluronic Acid-Based Smart Nanoconjugates for Enhanced Intracellular Drug Delivery
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