Anticancer Drugs: Recent Strategies to Improve Stability Profile, Pharmacokinetic and Pharmacodynamic Properties

Abstract

In past decades, anticancer research has led to remarkable results despite many of the approved drugs still being characterized by high systemic toxicity mainly due to the lack of tumor selectivity and present pharmacokinetic drawbacks, including low water solubility, that negatively affect the drug circulation time and bioavailability. The stability studies, performed in mild conditions during their development or under stressing exposure to high temperature, hydrolytic medium or light source, have demonstrated the sensitivity of anticancer drugs to many parameters. For this reason, the formation of degradation products is assessed both in pharmaceutical formulations and in the environment as hospital waste. To date, numerous formulations have been developed for achieving tissue-specific drug targeting and reducing toxic side effects, as well as for improving drug stability. The development of prodrugs represents a promising strategy in targeted cancer therapy for improving the selectivity, efficacy and stability of active compounds. Recent studies show that the incorporation of anticancer drugs into vesicular systems, such as polymeric micelles or cyclodextrins, or the use of nanocarriers containing chemotherapeutics that conjugate to monoclonal antibodies can improve solubility, pharmacokinetics, cellular absorption and stability. In this study, we summarize the latest advances in knowledge regarding the development of effective highly stable anticancer drugs formulated as stable prodrugs or entrapped in nanosystems.

Lipid Nanoparticles Functionalized with Antibodies for Anticancer Drug Therapy

“…Particles within the size range of 10 to 1000 nm are defined as nanoparticles. Therapeutic agents (i.e., drugs, proteins, and genetic material) can also be adsorbed or chemically conjugated to the nanoparticle surface, but those that are dissolved, entrapped, or encapsulated into the nanoparticle will benefit from enhanced chemical stability and protection against degradation [ 18 ]. Another distinctive feature of nanoparticles is the large surface area/volume ratio compared to bulk materials upon reduction of particle size to the nanoscale [ 19 ].…”

Codelivery of Phytochemicals with Conventional Anticancer Drugs in Form of Nanocarriers

“…The requirement of higher doses of anticancer drugs leads to increased toxicities in non-cancerous cells and multiple-drug resistance [ 28 ]. Furthermore, drug instability and low aqueous solubility of anticancer drugs also cause obstacles in treatment of cancer [ 29 ]. Drugs approved by the FDA to treat cancer have been summarized in Table 1 , along with their adverse effects.…”

Chitosan-Based Nano-Smart Drug Delivery System in Breast Cancer Therapy

“…Given the enormous cost of drug development, exacerbated by high failure rates, anticancer drugs are usually expensive. The search for a new delivery system is expected to find a solution that can increase the effectiveness and efficiency of the use of existing cancer drugs [ 98 , 99 ]. In building this delivery system, there are several strategies offered by chitosan, from various studies that have been conducted: CSNPs may encapsulate or conjugate chemotherapeutic medicines, therapeutic gene nucleic acids, photosensitizers, and cytokines for more reliable cancer target treatment [ 1 ].…”