Current Principles, Challenges, and New Metrics in pH-Responsive Drug Delivery Systems for Systemic Cancer Therapy

The paradigm of drug delivery via particulate formulations is one of the leading ideas that enable overcoming limitations of traditional chemotherapeutic agents. The trend toward more complex multifunctional drug carriers is well-traced in the literature. Nowadays, the prospectiveness of stimuli-res...

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Main Authors: Roman A. Verkhovskii, Alexey N. Ivanov, Ekaterina V. Lengert, Ksenia A. Tulyakova, Natalia Yu. Shilyagina, Alexey V. Ermakov
Format: Article
Language:English
Published: MDPI AG 2023-05-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/15/5/1566
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author Roman A. Verkhovskii
Alexey N. Ivanov
Ekaterina V. Lengert
Ksenia A. Tulyakova
Natalia Yu. Shilyagina
Alexey V. Ermakov
author_facet Roman A. Verkhovskii
Alexey N. Ivanov
Ekaterina V. Lengert
Ksenia A. Tulyakova
Natalia Yu. Shilyagina
Alexey V. Ermakov
author_sort Roman A. Verkhovskii
collection DOAJ
description The paradigm of drug delivery via particulate formulations is one of the leading ideas that enable overcoming limitations of traditional chemotherapeutic agents. The trend toward more complex multifunctional drug carriers is well-traced in the literature. Nowadays, the prospectiveness of stimuli-responsive systems capable of controlled cargo release in the lesion nidus is widely accepted. Both endogenous and exogenous stimuli are employed for this purpose; however, endogenous pH is the most common trigger. Unfortunately, scientists encounter multiple challenges on the way to the implementation of this idea related to the vehicles’ accumulation in off-target tissues, their immunogenicity, the complexity of drug delivery to intracellular targets, and finally, the difficulties in the fabrication of carriers matching all imposed requirements. Here, we discuss fundamental strategies for pH-responsive drug delivery, as well as limitations related to such carriers’ application, and reveal the main problems, weaknesses, and reasons for poor clinical results. Moreover, we attempted to formulate the profiles of an “ideal” drug carrier in the frame of different strategies drawing on the example of metal-comprising materials and considered recently published studies through the lens of these profiles. We believe that this approach will facilitate the formulation of the main challenges facing researchers and the identification of the most promising trends in technology development.
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spelling doaj.art-3c2ce02697d94f4e8db3dabe3e8cf16e2023-11-18T02:53:23ZengMDPI AGPharmaceutics1999-49232023-05-01155156610.3390/pharmaceutics15051566Current Principles, Challenges, and New Metrics in pH-Responsive Drug Delivery Systems for Systemic Cancer TherapyRoman A. Verkhovskii0Alexey N. Ivanov1Ekaterina V. Lengert2Ksenia A. Tulyakova3Natalia Yu. Shilyagina4Alexey V. Ermakov5Science Medical Center, Saratov State University, 83 Astrakhanskaya Str., 410012 Saratov, RussiaCentral Research Laboratory, Saratov State Medical University of V. I. Razumovsky, Ministry of Health of the Russian Federation, 410012 Saratov, RussiaCentral Research Laboratory, Saratov State Medical University of V. I. Razumovsky, Ministry of Health of the Russian Federation, 410012 Saratov, RussiaInstitute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603950 Nizhny Novgorod, RussiaInstitute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603950 Nizhny Novgorod, RussiaCentral Research Laboratory, Saratov State Medical University of V. I. Razumovsky, Ministry of Health of the Russian Federation, 410012 Saratov, RussiaThe paradigm of drug delivery via particulate formulations is one of the leading ideas that enable overcoming limitations of traditional chemotherapeutic agents. The trend toward more complex multifunctional drug carriers is well-traced in the literature. Nowadays, the prospectiveness of stimuli-responsive systems capable of controlled cargo release in the lesion nidus is widely accepted. Both endogenous and exogenous stimuli are employed for this purpose; however, endogenous pH is the most common trigger. Unfortunately, scientists encounter multiple challenges on the way to the implementation of this idea related to the vehicles’ accumulation in off-target tissues, their immunogenicity, the complexity of drug delivery to intracellular targets, and finally, the difficulties in the fabrication of carriers matching all imposed requirements. Here, we discuss fundamental strategies for pH-responsive drug delivery, as well as limitations related to such carriers’ application, and reveal the main problems, weaknesses, and reasons for poor clinical results. Moreover, we attempted to formulate the profiles of an “ideal” drug carrier in the frame of different strategies drawing on the example of metal-comprising materials and considered recently published studies through the lens of these profiles. We believe that this approach will facilitate the formulation of the main challenges facing researchers and the identification of the most promising trends in technology development.https://www.mdpi.com/1999-4923/15/5/1566cancer therapynanomedicinedrug deliverypH-responsivenessEPRintratumoral delivery
spellingShingle Roman A. Verkhovskii
Alexey N. Ivanov
Ekaterina V. Lengert
Ksenia A. Tulyakova
Natalia Yu. Shilyagina
Alexey V. Ermakov
Current Principles, Challenges, and New Metrics in pH-Responsive Drug Delivery Systems for Systemic Cancer Therapy
Pharmaceutics
cancer therapy
nanomedicine
drug delivery
pH-responsiveness
EPR
intratumoral delivery
title Current Principles, Challenges, and New Metrics in pH-Responsive Drug Delivery Systems for Systemic Cancer Therapy
title_full Current Principles, Challenges, and New Metrics in pH-Responsive Drug Delivery Systems for Systemic Cancer Therapy
title_fullStr Current Principles, Challenges, and New Metrics in pH-Responsive Drug Delivery Systems for Systemic Cancer Therapy
title_full_unstemmed Current Principles, Challenges, and New Metrics in pH-Responsive Drug Delivery Systems for Systemic Cancer Therapy
title_short Current Principles, Challenges, and New Metrics in pH-Responsive Drug Delivery Systems for Systemic Cancer Therapy
title_sort current principles challenges and new metrics in ph responsive drug delivery systems for systemic cancer therapy
topic cancer therapy
nanomedicine
drug delivery
pH-responsiveness
EPR
intratumoral delivery
url https://www.mdpi.com/1999-4923/15/5/1566
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