Clinical experience with drug delivery systems as tools to decrease the toxicity of anticancer chemotherapeutic agents

Abstract

The toxicity of chemotherapeutic agents, resulting from their low pharmacological index, introduces considerable discomfort and risk to cancer patients. Among several strategies to reduce the toxicity of chemotherapeutic agents, targeted drug delivery is the most promising one. Areas covered: Liposomes, micelles, albumin-based, polymeric, dendritic and lipid core nanoparticles have been used as carriers to concentrate anticancer drugs in neoplastic tissues, and clinical studies of those preparations are reviewed. In most clinical studies, drug delivery systems reduced drug toxicity. Lipid core nanoparticles (LDE) that bind to cell lipoprotein receptors have the ability to concentrate in neoplastic tissues and were the first artificial non-liposomal system shown in in vivo studies to possess targeting properties. The toxicity reduction achieved by LDE as vehicle of carmustine, etoposide and paclitaxel was singularly strong. Expert opinion: The reduced toxicity offered by drug delivery systems has expanded treatment population that may benefit from chemotherapy including feeble, overtreated and elderly patients that would otherwise be offered palliative therapy. Drug delivery systems may either prolong the duration of treatments or allow increases in drug dose.

Nanomedicine review: clinical developments in liposomal applications

“…The amphiphilic phospholipid bilayer of liposomes has close resemblance to the mammalian cell membrane, enabling efficient interactions between liposomes and cell membrane and subsequently effective cellular uptake (Gonda et al 2019). In addition, liposomes may be added with ligands to increase efficiency and specifically target damaged cells, thus improving liposome pharmacokinetics and their ability to pass through target membranes, reaching high concentrations inside cells while reducing toxicity and enhancing treatment efficacy (Li et al 2014;Ud Din et al 2017;Zamani et al 2018;Hussain et al 2017;Lombardo et al 2016;Fouladi et al 2017;Maranhão et al 2017;Miller et al 2016). For instance, MM-302, an antibody-liposomal doxorubicin conjugate, specifically targets HER2 overexpressing cells (Miller et al 2016).…”

Tissue Uptake Mechanisms Involved in the Clearance of Non‐Protein Nanoparticles that Mimic LDL Composition: A Study with Knockout and Transgenic Mice

“…LDE, constituted of nanoparticles with an average 40-60 nm, is not likely to cross the brain-blood barrier. The pioneer observation that LDE can target neoplastic and inflammatory, atherosclerotic tissues, leading to marked reduction of the toxicity of chemotherapeutic agents and an increase in their pharmacological action, was reiterated in several experimental and clinical studies [18,19]. The results of this study support LDLR and apoE as key players for LDE clearance but suggest that other receptor mechanisms may also have a role in the tissue uptake of this nanoparticle system.…”

“…The pioneer observation that LDE can target neoplastic and inflammatory, atherosclerotic tissues, leading to marked reduction of the toxicity of chemotherapeutic agents and an increase in their pharmacological action, was reiterated in several experimental and clinical studies [18,19]. LDE, constituted of nanoparticles with an average 40-60 nm, is not likely to cross the brain-blood barrier.…”

“…As described above, LDE has great potential as a drug delivery system for the treatment of cancer, atherosclerosis and other chronic inflammatory diseases [18,19]. As described above, LDE has great potential as a drug delivery system for the treatment of cancer, atherosclerosis and other chronic inflammatory diseases [18,19].…”

“…Non-protein, LDL-like nanoparticles with defined lipid composition such as LDE are easy to prepare and label by radioactive and other means and can be used as a tool to explore the plasma lipoprotein metabolism. As described above, LDE has great potential as a drug delivery system for the treatment of cancer, atherosclerosis and other chronic inflammatory diseases [18,19]. Although LDE has a wide distribution in the organs and tissues, the concentration in tumoral tissues, compared to the corresponding normal tissues is remarkable.…”