Dominika Kunachowicz, Karolina Kłosowska, Daria Konarska, Marta Kepinska

Novel and conventional formulations of doxorubicin as a key anticancer agent – a literature review

2024-10-24

Study subject. Doxorubicin (DOX), a cytotoxic drug classified as anthracycline antibiotic, has been one of the most important pharmacological tools in anticancer therapy for decades. Despite its introduction to the clinic in the 1970s, due to the high effectiveness and wide range of use, DOX remains irreplaceable in many treatment regimens for both solid tumors and hematological cancers. However, DOX-based therapies are associated with a high risk of numerous limiting adverse effects. These include non-specific effects common to cytostatics resulting from their lack of selectivity towards cancer cells, such as bone marrow suppression, hepatotoxicity, mucositis, and gastrointestinal symptoms, as well as DOX-specific cardiotoxicity. Cardiac muscle damage resulting from the use of this drug is the most serious side effect, often leading to death. Another major clinical problem is the development of resistance to DOX by cancer cells. Moreover, free DOX after systemic administration poorly penetrates into cancer cells, which further limits its effectiveness. Therefore, considerable efforts are being made to develop new targeted therapy solutions, which - often based on nanotechnology - will increase the effectiveness of treatment while minimizing the associated toxicity towards healthy, rapidly dividing cells. It is expected that more effective DOX formulations will allow for the reduction of the drug dose and could be applied in more intensive and/or longer therapy in advanced cancers, as well as in patients with disease recurrence.

Research objective. The aim of the study was to present and systematize the current state of knowledge concerning targeted DOX formulations, their advantages in comparison to standard therapeutic strategies, as well as their limitations. Liposomes, micelles, nanogels, polymeric nanoparticles, and quantum dots with fullerenes have been characterized as DOX carriers. Both clinically used solutions and those evaluated in various stages of preclinical research have been discussed.

Literature search and selection methodology. The analysis of scientific publications deposited in the PubMed and Google Scholar databases since 2015 was performed. The search of relevant articles was carried out throughout May and June 2024, with the use of keywords: “doxorubicin”, “targeted therapies”, “doxorubicin formulations”, “conventional/ standard therapeutic approaches”, and “nanosystems”.

Results. The research results presented in this paper indicate that rapidly developing nanomedicine may be a solution to increase the effectiveness and safety of DOX therapy. In general, systems of DOX targeted delivery have been shown to exhibit lower systemic toxicity as well as better accumulation in cancer cells than the free drug.

Conclusions. Development and continuous optimization of DOX formulations is the right strategy, opening prospects for improving anticancer therapies based on this clinically important drug. Although currently only liposomal DOX is in clinical use, based on extensive in vitro studies and animal models, an increase in the number of DOX nanoformulations submitted to clinical trials can be expected. The manuscript is a comprehensive study on the principles of standard DOX therapy, its mechanisms of action, and clinical parameters, as well as progress in the development of modern targeted DOX therapies using nanocarriers.

Keywords: doxorubicin, oncology, targeted therapy, drug delivery, nanotechnology.

© Farm Pol, 2024, 80(5): 317–330