<p>In vivo Bio-Distribution and Toxicity Evaluation of Polymeric and Lipid-Based Nanoparticles: A Potential Approach for Chronic Diseases Treatment</p>

Abstract

Introduction: Nanoparticles (NPs), as drug delivery systems, appear to be a promising tool for prolonged therapeutic strategies as they allow a controlled drug release over time. However, most of the studies found in the literature simply contemplate the use of a single or low number of dosages with low NPs concentrations. In the context of chronic diseases, like Alzheimer's disease, cancer or human immunodeficiency virus (HIV), where the therapeutic scheme is also chronic, studies with numerous repeated dosages are often neglected. Methods: We screened different NPs, polymeric and lipid-based, in a repeated-dose toxicity study, to evaluate the safety and tissue distribution of promising nanocarriers to be used in the treatment of long-lasting diseases. Results: After administrating 24 high concentrated doses of the selected NPs intraperitoneally (i.p.) (3 times a week for 2 months), animals have presented NPs accumulation in different tissues. However, neither toxicity, bodyweight changes nor clinical signs of disease were observed. Discussion: This work demonstrates no general adverse effects upon the studied NPs repeated-dose exposure, indicating the most promising NPs to be used in the different therapeutic circumstances, which may be useful in chronic diseases treatment.

Single-cell analysis reveals effective siRNA delivery in brain tumors with microbubble-enhanced ultrasound and cationic nanoparticles

“…Increasing the sample size of each experimental group (table S2) will allow to assess further the reproducibility of our findings and better assess how tumor heterogeneity affects the proposed therapeutic strategy. Although past biodistribution and toxicity investigations of lipid nanoparticles with similar dosage to the one that we used in this study reported negligible toxicity (41)(42)(43), future studies in evaluating treatment outcomes (tumor growth and survival) in patient-derived tumors with and without known driver mutations, combined with extended toxicologic analysis under different LPH:siRNA doses, are warranted. Testing additional FUS exposures (e.g., lower harmonic emissions), ideally under closed-loop control (52)(53)(54)(55), combined with a more detailed assessment of the BBB phenotype (i.e., structure and function) and brain/tumor tissue (56,57) will allow to further define and refine the MB-FUS treatment window for safe and effective siRNA delivery in the brain TME.…”

“…For these investigations, we used (i) a 0.5-MHz transducer with standard exposure settings (10-ms bursts, every 1 s for 1 min, at 475-kPa peak negative pressure in water), (ii) Optison (GE Healthcare) MBs with a dosage of 100 l/kg, and (iii) RhoB-LPH nanoparticles (5 mg/kg). The in vivo dosage of nanoparticle was decided on the basis of the dosages used in previous studies that showed that this nanoparticle dose led to minimal side effects (41)(42)(43). Fluorescence imaging of the excised brain 10 min after sonication indicated a 12fold increase in the extravasation of LPH in the FUS-treated region as compared to the non-FUS region (P < 0.0001) (Fig.…”

Cobalt Ferrite Nanoparticles for Tumor Therapy: Effective Heating versus Possible Toxicity

“…injection, the following organs of the animals underwent histological examination: lymph node, spleen, liver, kidney, stomach, intestines, heart, lungs, brain, testis, and ovaries. These organs are usually analyzed in the in vivo studies of MNPs toxicity [ 29 , 30 ]. Similar results were obtained for mice and rats.…”

Polymeric Nanoparticles-Loaded Hydrogels for Biomedical Applications: A Systematic Review on In Vivo Findings

“…PLGA NPs are biocompatible, Food and Drug Administration (FDA) approved [ 54 ], and safe for repeat-dose exposure in vivo [ 55 ], being widely explored for incorporation in hydrogels for drug delivery. Wang et al (2021) developed a hydrogel composed of poly (ethylene glycol) diacrylate (PEGDA) and HA for the local delivery of paclitaxel for lung cancer therapy [ 26 ].…”