Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 3 May 2023 / Approved: 5 May 2023 / Online: 5 May 2023 (03:45:54 CEST)

A peer-reviewed article of this Preprint also exists.

Verkhovskii, R.A.; Ivanov, A.N.; Lengert, E.V.; Tulyakova, K.A.; Shilyagina, N.Y.; Ermakov, A.V. Current Principles, Challenges, and New Metrics in pH-Responsive Drug Delivery Systems for Systemic Cancer Therapy. Pharmaceutics 2023, 15, 1566. Verkhovskii, R.A.; Ivanov, A.N.; Lengert, E.V.; Tulyakova, K.A.; Shilyagina, N.Y.; Ermakov, A.V. Current Principles, Challenges, and New Metrics in pH-Responsive Drug Delivery Systems for Systemic Cancer Therapy. Pharmaceutics 2023, 15, 1566.

Abstract

The paradigm of drug delivery via nano- and microcarriers is one of the leading ideas that enable overcoming the limitations of traditional chemotherapy. The trend toward more complex drug carriers capable of multifunctionality is observed in the literature. To date, prospects of stimuli-responsive systems to control the cargo release in the lesion nidus are widely accepted. Both endogenous and exogenous stimuli are employed for this purpose, however, endogenous pH is one of the most common triggers. Unfortunately, scientists face difficulties in the implementation of this idea since a range of biological barriers, drug bioavailability issues, and challenges in the synthesis of carriers with required properties have arisen. Here, we discuss fundamental strategies of pH-responsive drug delivery as well as limits in its application and reveal the main problems, weak sides, and reasons for poor clinical results. Also, we have made an attempt to formulate the profiles of "ideal" drug carrier in the frame of different strategies and considered recently published studies through the lens of these profiles. This approach enables the identification of current trends and promising vectors in the development of pH-responsive drug delivery systems, as well as challenges to be resolved in the next generation of carriers.

Keywords

cancer therapy; nanomedicine; drug delivery; pH-responsiveness; EPR; intratumoral delivery; intracellular delivery; nanoparticles; metal-organic frameworks

Subject

Chemistry and Materials Science, Nanotechnology

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