Unintended effects of drug carriers: Big issues of small particles

Abstract

Humoral and cellular host defense mechanisms including diverse phagocytes, leukocytes, and immune cells have evolved over millions of years to protect the body from microbes and other external and internal threats. These policing forces recognize engineered sub-micron drug delivery systems (DDS) as such a threat, and react accordingly. This leads to impediment of the therapeutic action, extensively studied and discussed in the literature. Here, we focus on side effects of DDS interactions with host defenses. We argue that for nanomedicine to reach its clinical potential, the field must redouble its efforts in understanding the interaction between drug delivery systems and the host defenses, so that we can engineer safer interventions with the greatest potential for clinical success.

Recent Advances in Bioplastics: Application and Biodegradation

“…In addition, the DDS have to be capable of maximum encapsulation efficiency of the target drug [84] have increased residence time in the target tissue, maximum bioavailability to achieve a therapeutic effect, and biodegradation in a timeframe compatible with the healing of the target tissue [85]. At the same time these biodegradable polymers should be safe; i.e., not inducing in vivo toxicity and not promoting an inflammatory response by the immunological system [86]. The physico-chemical features of the biodegradable polymer that dictate their success as nanocarriers are: polymeric composition, surface charge, molecular weight of the polymer, tacticity of the monomers, colloidal stability, size distribution of the nanoparticles, minimization of nanoparticle aggregation, and their hydrophilicity to hydrophobicity ratio [87].…”

Recent Advances in Nanocarrier-Assisted Therapeutics Delivery Systems

“…Even for nanocarriers composed of biocompatible materials and carrying benign cargos, it is still possible that they may elicit pro-inflammatory effects [180]. Many unintended side effects may occur in major organs due to the size, shape, or charge of the nanocarriers [181]. Therefore, systemic effects of the nanocarriers, such as activation of complement, coagulation or the platelets, and toxicity toward the clearing tissues (liver, kidney, lungs, etc.…”

“…In order to alleviate the side effects when interacting with host defenses, Parhiz et al also suggested several approaches as alternative modification or functionalization of those nanocarriers. For example, using hydroxyethyl starch (HES), polysialic acid, dextrin, and poly(phosphoester)s (PPEs) as an alternative for PEG, because PEG-specific antibodies have been found to be generated following administration of PEGylated liposomes, accelerating the clearing process of those liposomes [181]. Other suggestions include replacing the antibodies with safer fragments or inducing immune tolerance of the host using various approaches [181].…”

Erythrocytes as Carriers: From Drug Delivery to Biosensors

“…Injection of artificial carriers can activate the complement system, induce the formation of reactive oxygen species, autophagy, inflammation and other toxic side effects. The review by Parhiz et al [150] discusses in detail the limitations and undesirable side effects of NCs, including biodegradability and biocompatibility ones. In contrast to synthetic capsules, RBCs are well-studied, can be readily obtained and in many ways represent ideal biocompatible and biodegradable drug carriers for intravascular delivery.…”