Population pharmacokinetic modelling of indium-based quantum dot nanoparticles: preclinical in vivo studies

Yaghini, Elnaz; Tacconi, Elisa; Pilling, Andrew; Rahman, Paula; Broughton, Joe; Naasani, Imad; Keshtgar, Mohammed; MacRobert, Alexander J.; Pasqua, Oscar Della

doi:10.1016/j.ejps.2020.105639

Cited by 13 publications

(12 citation statements)

References 30 publications

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“…γ is a function of surface morphology (shape), 155,208 but applicability to non-spherical NPs remains speculation, needing further study. Long-term exposures to various NPs/coatings (PbO, TiO 2 , QDs, C 60 , citrate 61,209–214 ) show distributions similar to Fig. 2 and values, e.g.…”

Section: Discussionsupporting

confidence: 66%

Nanoparticles in bodily tissues: predicting their equilibrium distributions

Nolte

Hendriks

2023

Environ. Sci.: Nano

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Section: Discussionsupporting

confidence: 66%

Nanoparticles in bodily tissues: predicting their equilibrium distributions

Nolte

Hendriks

2023

Environ. Sci.: Nano

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“…This is not the case for CAROL. The negligible serum indium concentration of our data is certainly free from in-vivo toxicity 50 .…”

Section: Discussionmentioning

confidence: 71%

A novel bronchoscopic guided non-invasive treatment for lung nodule

Kim

Shah²,

Seol³

et al. 2023

Preprint

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Radiofrequencyablation (RFA) is one of the treatment options for lung nodules; however, the need for exact delivery of the rigid metal electrode into the center of the target mass often leads to complications or suboptimal results. To overcome these limitations, we report a novel bronchoscopy-guided atraumatic no-touch RFA procedure that uses a specially designed radiofrequency (RF) conductor balloon catheter (CAROL catheter) and an injectable bronchial electrode based on a medical grade liquid metal (E-GaIn) in porcine lungs. The bronchial electrode injected from the CAROL catheter was able to turn the target-site bronchial air pipe into a temporally multi-tined RF electrode. The mean volume of E-GaIn (bronchial electrode) for each effective CAROL was 0.46 ± 0.47 ml. The ablation results showed highly efficacious and consistent results especially in the peripheral lung. Most bronchial electrodes were also retrieved by either bronchoscopic suction immediately after the procedure or by natural expectoration thereafter. The residual bronchial electrode did not cause any significant safety issues. Our computer simulation model also supported preclinical data.

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“…An additional reason for the complexity of the PK associated with genetic vaccines is their requirement to be engineered and packaged into specific nano carriers (e.g., adenovirus carriers or lipid nanoparticles) to enable efficient delivery to targeted cells and maintain biostability and bioavailability [8]. Being in a nano format implies an exceptional PK mode that is non-linear [9] and saturable, meaning that the doseexposure correlation is subject to Michaelis-Menten type of saturation kinetics [10][11][12][13][14][15]. Thus, any minor variabilities in tissue levels can result in major variability in clinical outcome.…”

Section: Key Pointsmentioning

confidence: 99%

Establishing the Pharmacokinetics of Genetic Vaccines is Essential for Maximising their Safety and Efficacy

Naasani¹

2022

Clin Pharmacokinet

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In a typical course of drug development, thorough pharmacokinetic (PK) studies are essential for the determination of drug biodistribution, dosage and efficacy without toxicity. For vaccines, however, unless a new formulation component is used, most regulatory agencies rule out the need for studying the biodistribution of the vaccine antigenic material per se, and only dose-immunogenicity studies are performed. This is because traditional vaccines are meant to directly induce immunogenicity by locally recruiting immunocytes that will carry on with the pursuing immunogenic processes. Thus, the clinical outcome from traditional vaccines is determined mainly by an immunological response phase. Yet, the case is significantly different for the emergent genetic vaccines (vectorised DNA or mRNA vaccines), where the clinical outcome is dependent on a combination of two major response phases: a pharmacological phase that involves biodistribution, assimilation, gene translation and epitope(s) presentation, followed by an immunological phase, which is similar to that of traditional vaccines. From a mathematical perspective, processes involved in drug administration are typically subject to inter-and intra-patient statistical distributions like most physiological processes. Therefore, the clinical outcome after administering genetic vaccines obeys a statistical probability distribution combined of the sum of two major response probability distributions, pharmacological and immunological. This implies that the variance coefficient of the summed response probability distributions has a larger value than the variance of each underlying distribution. In other words, due to the multi-phased mode of action of genetic vaccines, their clinical outcome has more variability than that of traditional vaccines. This observation points toward the necessity for regulating genetic vaccines in a similar manner to bio-therapeutics to ensure better efficacy and safety. A structural PK model is provided to predict the sources of variability, biodistribution and dose optimisation.

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Population pharmacokinetic modelling of indium-based quantum dot nanoparticles: preclinical in vivo studies

Cited by 13 publications

References 30 publications

Nanoparticles in bodily tissues: predicting their equilibrium distributions

Nanoparticles in bodily tissues: predicting their equilibrium distributions

A novel bronchoscopic guided non-invasive treatment for lung nodule

Establishing the Pharmacokinetics of Genetic Vaccines is Essential for Maximising their Safety and Efficacy

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