Lung retention and particokinetics of silver and gold nanoparticles in rats following subacute inhalation co-exposure

Background Inhalation exposure to nanomaterials in workplaces can include a mixture of multiple nanoparticles. Such ambient nanoparticles can be of high dissolution or low dissolution in vivo and we wished to determine whether co-exposure to particles with different dissolution rates affects their biokinetics. Methods and Results Rats were exposed to biosoluble silver nanoparticles (AgNPs, 10.86 nm) and to biopersistent gold nanoparticles (AuNPs, 10.82 nm) for 28 days (6-h/day, 5-days/week for 4 weeks) either with separate NP inhalation exposures or with combined co-exposure. The separate NPs mass concentrations estimated by the differential mobility analyzer system (DMAS) were determined to be 17.68 ± 1.69 μg/m3 for AuNP and 10.12 ± 0.71 μg/m3 for AgNP. In addition, mass concentrations analyzed by atomic absorption spectrometer (AAS) via filter sampling were for AuNP 19.34 ± 2.55 μg/m3 and AgNP 17.38 ± 1.88 μg/m3 for separate exposure and AuNP 8.20 ± 1.05 μg/m3 and AgNP 8.99 ± 1.77 μg/m3 for co-exposure. Lung retention and clearance were determined on day 1 (6-h) of exposure (E-1) and on post-exposure days 1, 7, and 28 (PEO-1, PEO-7, and PEO-28, respectively). While the AgNP and AuNP deposition rates were determined to be similar due to the similarity of NP size of both aerosols, the retention half-times and clearance rates differed due to the difference in dissolution rates. Thus, when comparing the lung burdens following separate exposures, the AgNP retention was 10 times less than the AuNP retention at 6-h (E-1), and 69, 89, and 121 times lower less than the AuNP retention at PEO-1, PEO-7, and PEO-28, respectively. In the case of AuNP+AgNP co-exposure, the retained AgNP lung burden was 14 times less than the retained AuNP lung burden at E-1, and 26, 43, and 55 times less than the retained AuNP lung burden at PEO-1, PEO-7, and PEO-28, respectively. The retention of AuNP was not affected by the presence of AgNP, but AgNP retention was influenced in the presence of AuNP starting at 24 h after the first day of post day of exposure. The clearance of AgNPs of the separate exposure showed 2 phases; fast (T1/2 3.1 days) and slow (T1/2 48.5 days), while the clearance of AuNPs only showed one phase (T1/2 .81.5 days). For the co-exposure of AuNPs+AgNPs, the clearance of AgNPs also showed 2 phases; fast (T1/2 2.2 days) and slow (T1/2 28.4 days), while the clearance of AuNPs consistently showed one phase (T1/2 54.2 days). The percentage of Ag lung burden in the fast and slow clearing lung compartment was different between separate and combined exposure. For the combined exposure, the slow and fast compartments were each 50% of the lung burden. For the single exposure, 1/3 of the lung burden was cleared by the fast rate and 2/3 of the lung burden by the slow rate. Conclusions The clearance of AgNPs follows a two- phase model of fast and slow dissolution rates while the clearance of AuNPs could be described by a one- phase model with a longer half-time. The co-exposure of AuNPs+AgNPs showed that the clearance of AgNPs was altered by the presence of AuNPs perhaps due to some interaction between AgNP and AuNP affecting dissolution and/or mechanical clearance of AgNP in vivo.

Pharmacokinetic Research Progress of Anti-tumor Drugs Targeting for Pulmonary Administration

Background:: Cancer is a major problem that threatens human survival and has a high mortality rate. The traditional chemotherapy methods are mainly intravenous injection and oral administration, but have obvious toxic and side effects. Anti-tumor drugs for pulmonary administration can enhance drug targeting, increase local drug concentration, and reduce the damage to systemic organs, especially for the treatment of lung cancer. Methods:: The articles on the pharmacokinetics of anti-tumor drugs targeting pulmonary administration were retrieved from the Pub Med database. This article mainly took lung cancer as an example and summarized the pharmacokinetic characteristics of anti-tumor drugs targeting for pulmonary administration contained in nanoparticles, dendrimers, liposomes and micelles. Results:: The review shows that the pharmacokinetics process of pulmonary administration is associated with a drug carrier by increasing the deposition and release of drugs in the lung, and retarding the lung clearance rate. Among them, the surface of dendrimers could be readily modified, and polymer micelles have favorable loading efficiency. In the case of inhalation administration, liposomes exhibit more excellent lung retention properties compared to other non-lipid carriers. Therefore, the appropriate drug carrier is instrumental to increase the curative effect of anti-tumor drugs and reduce the toxic effect on surrounding healthy tissues or organs. Conclusion:: In the process of pulmonary administration, the carrier-embedded antitumor drugs have the characteristics of targeted and sustained release compared with non-packaging drugs, which provides a theoretical basis for the clinical rational formulation of chemotherapy regimens. However, there is currently a lack of comparative research between drug packaging materials, and more importantly, the development of safe and effective anti-tumor drugs targeting for pulmonary administration requires more data.