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Drug Delivery: Overview01:16

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The selection of a drug's delivery route depends upon its physicochemical properties, including lipid or water solubility and ionization, as well as the therapeutic requirement, such as immediate or sustained effect. These routes can be divided into three primary categories: enteral, parenteral, and topical.
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The enteral drug administration involves three primary routes: oral, sublingual, and buccal. Oral ingestion is the most prevalent, safe, economical, and convenient method for drug administration. However, it has certain drawbacks, including limited absorption due to the drug's low water solubility or poor membrane permeability, possible emesis from GI mucosa irritation, destruction of drugs by digestive enzymes or low gastric pH, and irregular absorption along with food or other drugs.
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iRGD-decorated reduction-responsive nanoclusters for targeted drug delivery.

Hang Hu1, Jiangling Wan2, Xuetao Huang1

  • 1Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China. zifuli@hust.edu.cn yangxl@hust.edu.cn.

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Novel nanoclusters (NCs) designed for targeted drug delivery specifically bind to cancer cells. These reduction-responsive NCs release drugs within cells, enhancing antitumor effects and showing promise for cancer therapy.

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Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Drug Delivery Systems

Background:

  • Targeted drug delivery aims to improve therapeutic efficacy and reduce side effects.
  • Nanocarriers offer potential for enhanced drug loading and controlled release.
  • Stimuli-responsive materials can enable site-specific drug release.

Purpose of the Study:

  • To develop reduction-responsive disintegratable nanoclusters (NCs) for targeted drug delivery.
  • To investigate the targeting efficiency and drug release capabilities of iRGD-decorated NCs.
  • To evaluate the in vitro antitumor efficacy of the developed nanoplatform.

Main Methods:

  • Self-assembly of iRGD-decorated hydroxyethyl starch (iRGD-HES-SS-C18) into nanoclusters (NCs).
  • Loading of doxorubicin (DOX) into the NCs (DOX@iRGD-HES-SS-C18).
  • In vitro evaluation of NCs' targeting specificity, cellular uptake, drug release under reductive stimuli, and antitumor activity against HepG-2 and 4T1 cells.

Main Results:

  • Successfully prepared iRGD-decorated, reduction-responsive, disintegratable nanoclusters (NCs) of approximately 170 nm.
  • DOX@iRGD-HES-SS-C18 NCs demonstrated specific binding and enhanced cellular uptake in integrin αV-positive HepG-2 and 4T1 cells.
  • Reductive environment triggered NC disintegration and DOX release, leading to superior in vitro antitumor effects compared to non-targeted NCs and free DOX.

Conclusions:

  • The developed reduction-responsive disintegratable NCs serve as a safe and efficient nanoplatform for targeted drug delivery.
  • The iRGD targeting ligand facilitates specific accumulation of NCs in cancer cells.
  • This nanoplatform holds significant potential for translation in tumor-targeted cancer therapy.