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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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Updated: Jul 29, 2025

Preparation and Characterization of Lipophilic Doxorubicin Pro-drug Micelles
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Current Principles, Challenges, and New Metrics in pH-Responsive Drug Delivery Systems for Systemic Cancer Therapy.

Roman A Verkhovskii1, Alexey N Ivanov2, Ekaterina V Lengert2,3

  • 1Science Medical Center, Saratov State University, 83 Astrakhanskaya Str., 410012 Saratov, Russia.

Pharmaceutics
|May 27, 2023
PubMed
Summary

pH-responsive drug delivery systems offer promise for cancer therapy but face challenges. This review analyzes strategies, limitations, and ideal carrier profiles to guide future development in stimuli-responsive drug carriers.

Keywords:
EPRcancer therapydrug deliveryintracellular deliveryintratumoral deliverymetal–organic frameworksnanomedicinenanoparticlespH-responsiveness

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Area of Science:

  • Biomedical Engineering
  • Materials Science
  • Pharmacology

Background:

  • Particulate drug delivery systems are crucial for overcoming limitations of traditional chemotherapeutics.
  • Stimuli-responsive drug carriers, particularly those triggered by endogenous pH, are a significant trend.
  • Challenges include off-target accumulation, immunogenicity, intracellular delivery, and fabrication complexities.

Purpose of the Study:

  • To discuss fundamental strategies for pH-responsive drug delivery.
  • To analyze limitations, problems, and reasons for poor clinical outcomes of pH-responsive carriers.
  • To define the profile of an 'ideal' drug carrier for pH-responsive delivery.

Main Methods:

  • Literature review of pH-responsive drug delivery strategies.
  • Analysis of challenges and limitations in carrier application.
  • Formulation of ideal drug carrier profiles using metal-comprising materials as examples.
  • Evaluation of recent studies against these ideal profiles.

Main Results:

  • pH-responsive drug delivery faces significant hurdles in clinical translation.
  • Existing carriers often exhibit off-target accumulation and fabrication difficulties.
  • Metal-comprising materials offer potential for developing improved pH-responsive carriers.

Conclusions:

  • A clear understanding of challenges is needed to advance pH-responsive drug delivery.
  • Defining ideal carrier profiles can guide technological development.
  • Future research should focus on overcoming current limitations for successful clinical application.