Nanomedicinal products: a survey on specific toxicity and side effects

Abstract

Due to their specific properties and pharmacokinetics, nanomedicinal products (NMPs) may present different toxicity and side effects compared to non-nanoformulated, conventional medicines. To facilitate the safety assessment of NMPs, we aimed to gain insight into toxic effects specific for NMPs by systematically analyzing the available toxicity data on approved NMPs in the European Union. In addition, by comparing five sets of products with the same active pharmaceutical ingredient (API) in a conventional formulation versus a nanoformulation, we aimed to identify any side effects specific for the nano aspect of NMPs. The objective was to investigate whether specific toxicity could be related to certain structural types of NMPs and whether a nanoformulation of an API altered the nature of side effects of the product in humans compared to a conventional formulation. The survey of toxicity data did not reveal nanospecific toxicity that could be related to certain types of structures of NMPs, other than those reported previously in relation to accumulation of iron nanoparticles (NPs). However, given the limited data for some of the product groups or toxicological end points in the analysis, conclusions with regard to (a lack of) potential nanomedicine-specific effects need to be considered carefully. Results from the comparison of side effects of five sets of drugs (mainly liposomes and/or cytostatics) confirmed the induction of pseudo-allergic responses associated with specific NMPs in the literature, in addition to the side effects common to both nanoformulations and regular formulations, eg, with liposomal doxorubicin, and possibly liposomal daunorubicin. Based on the available data, immunotoxicological effects of certain NMPs cannot be excluded, and we conclude that this end point requires further attention.

Preparation, Characterization, Cytotoxicity and Biological Evaluation of ^99mTc-Doxorubicin-Epigallocatechingallate Functionalized Gold Nanoparticles as a New Generation of Theranostic Radiopharmaceutical

“…Extensive preclinical studies have demonstrated that chronic administration of doxorubicin would result in a severe DRG (dorsal root ganglia) neuronopathy [33,34]. Therefore, current and future clinical applications of doxorubicin, as a first line cancer therapy drug, requires development of delivery technologies that would not only result in selective delivery at tumor sites but also enhance retention of therapeutic doses with minimal/no systemic side effects.…”

“…Doxorubicin is a chemotherapeutic agent being currently used for treating multiple types of cancers including breast cancer, bladder cancer, ovarian cancer, lymphoma, and acute lymphocytic leukemia. Common side effects of doxorubicin include cardiotoxicity, hair loss, bone marrow suppression, vomiting, rash, and inflammation of the mouth [33,34]. An important consideration is that conjugating doxorubicin with gold nanoparticles might reduce its side effects due to passive targeting of cancer tissue aided through enhanced permeability and retention effects (EPR) [35,36].…”

<p>Targeted Fe-doped silica nanoparticles as a novel ultrasound&ndash;magnetic resonance dual-mode imaging contrast agent for HER2-positive breast cancer</p>

“…[14][15][16][17] Although many studies showed good imaging or therapeutic results, safety and patient tolerance remained key to clinical conversion. [18][19][20] SiO 2 nanoparticles (NPs) are widely used in biomedical and other fields, because of their adjustable particle size, functionality, stability, and good biocompatibility. [21][22][23] Pohaku et al prepared a novel type of NP by doping iron(III) into hollow silica (HS) nanoshells, which could be degraded in serum at physiological temperature.…”

Nanomedicines: Challenges and perspectives for future nanotechnology in the healthcare system

“…Although nanomedicines are being formulated to get desired and highly effective diagnostic as well as less toxic treatment, but the main concern here is to assess the safety procedures, which are performed to evaluate the total quality and efficacy of nanomedicines. Essentially, the pharmacokinetic and pharmacodynamic profile of the formulated nanoparticles must be assessed for its toxicity and safety (Brand et al, 2017).…”