ABSTRACT
Many purine derivatives are active pharmaceutical ingredients of significant importance in the therapy of autoimmune diseases, cancers, and viral infections. In many cases, their medical use is limited due to unfavorable physicochemical and pharmacokinetic properties. These problems can be overcome by the preparation of the prodrugs of purines or by combining these compounds with nanoparticles. Herein, we aim to review the scientific progress and perspectives for polymer-based nanoparticles as drug delivery systems for purines. Polymeric nanoparticles turned out to have the potential to augment antiviral and antiproliferative effects of purine derivatives by specific binding to receptors (ASGR1-liver, macrophage mannose receptor), increase in drug retention (in eye, intestines, and vagina), and permeation (intranasal to brain delivery, PEPT1 transport of acyclovir). The most significant achievements of polymer-based nanoparticles as drug delivery systems for purines were found for tenofovir disoproxil in protection against HIV, for acyclovir against HSV, for 6-mercaptopurine in prolongation of mice ALL model life, as well as for 6-thioguanine for increased efficacy of adoptively transferred T cells. Moreover, nanocarriers were able to diminish the toxic effects of acyclovir, didanosine, cladribine, tenofovir, 6-mercaptopurine, and 6-thioguanine.
ABSTRACT
Flavonoids are polyphenolic compounds widely occurring throughout the plant kingdom. They are biologically active and have many medical applications. Flavonoids reveal chemopreventive, anticarcinogenic, and antioxidant properties, as well as being able to modulate the immune system response and inhibit inflammation, angiogenesis, and metastasis. Polyphenols are also believed to reverse multidrug resistance via various mechanisms, induce apoptosis, and activate cell death signals in tumor cells by modulating cell signaling pathways. The main limitation to the broader usage of flavonoids is their low solubility, poor absorption, and rapid metabolism. To tackle this, the combining of flavonoids with nanocarriers could improve their bioavailability and create systems of wider functionalities. Recently, interest in hybrid materials based on combinations of metal nanoparticles with flavonoids has increased due to their unique physicochemical and biological properties, including improved selectivity toward target sites. In addition, flavonoids have further utilities, even in the initial step of preparation of metal nanomaterials. The review offers knowledge on multiple possibilities of the synthesis of flavonoid-metal nanoparticle conjugates, as well as presents some of their features such as size, shape, surface charge, and stability. The flavonoid-metal nanoparticles are also discussed regarding their biological properties and potential medical applications.
