Structural modification and strategies for the enhanced doxorubicin drug delivery

Doxorubicin belongs to the anthracycline chemical class of the drug and is one of the widely used anticancer drugs. The common side effects of doxorubicin include vomiting, hair loss, rashes to serious side-effects such as irreversible cardiotoxicity, and drug-induced leukemia. This led many researchers around the globe to develop methods aimed to achieve higher efficacy and lower toxicity for doxorubicin. The present review article provides a detailed account of the design strategies i.e., chemical modifications and conjugate formation adopted by various research groups to minimize the side effects without compromising with the significant anticancer profile of the drug doxorubicin. Chemical modification of the drug includes alteration at C4' hydroxyl and C3' amine groups present in the sugar part. The pH-sensitive drug delivery system is covered highlighting use of theranostic tantalum oxide to the traditional approach of conjugating with acyl hydrazine and thiourea. Methods adopted to increase the bioavailability of the drugs inside the cancer cells viz., conjugation with humanized monoclonal antibody and other peptides along with their promising results are also discussed. The review further discusses works from recent years comprising of different nanoforms of doxorubicin for the targeted delivery of drugs inside the tumor cells. Few of the articles targeting nucleus or mitochondria as one of the effective cancer treatments are reported. The brain is inaccessible to the drug and it was modified through galactoxyloglucan-modified gold nanocarrier or conjugated with lactoferrin with enhanced permeability through the blood-brain barrier. Prodrug has particularly been used to target tumor tissues without affecting other tissue organs. The present review article offer clear advantages of one method over another adopted to target the cancer cells and may provide an insight for the researchers working in this area.