Effects of Particle Size and Surface Modification on Cellular Uptake and Biodistribution of Polymeric Nanoparticles for Drug Delivery

Kulkarni, Sneha A.; Feng, Si‐Shen

doi:10.1007/s11095-012-0958-3

Cited by 632 publications

(389 citation statements)

References 42 publications

Supporting

Mentioning

364

Contrasting

Unclassified

Order By: Relevance

“…In most studies, nanoparticle PK is determined by blood draws at specific time points after injection, combined with appropriate assays for determining the particle concentration in the blood (39,40). This method has the advantage of directly measuring the…”

Section: Discussionmentioning

confidence: 99%

Nanoparticle clearance is governed by Th1/Th2 immunity and strain background

Jones¹,

Roberts²,

Robbins³

et al. 2013

J. Clin. Invest.

177

164

View full text Add to dashboard Cite

Extended circulation of nanoparticles in blood is essential for most clinical applications. Nanoparticles are rapidly cleared by cells of the mononuclear phagocyte system (MPS). Approaches such as grafting polyethylene glycol onto particles (PEGylation) extend circulation times; however, these particles are still cleared, and the processes involved in this clearance remain poorly understood. Here, we present an intravital microscopybased assay for the quantification of nanoparticle clearance, allowing us to determine the effect of mouse strain and immune system function on particle clearance. We demonstrate that mouse strains that are prone to Th1 immune responses clear nanoparticles at a slower rate than Th2-prone mice. Using depletion strategies, we show that both granulocytes and macrophages participate in the enhanced clearance observed in Th2-prone mice. Macrophages isolated from Th1 strains took up fewer particles in vitro than macrophages from Th2 strains. Treating macrophages from Th1 strains with cytokines to differentiate them into M2 macrophages increased the amount of particle uptake. Conversely, treating macrophages from Th2 strains with cytokines to differentiate them into M1 macrophages decreased their particle uptake. Moreover, these results were confirmed in human monocyte-derived macrophages, suggesting that global immune regulation has a significant impact on nanoparticle clearance in humans. IntroductionThe potential clinical applications of nanoparticles and nanoformulations have been investigated for more than 30 years. Nanoparticle approaches have the potential to revolutionize drug delivery by allowing for the encapsulation of drugs with poor solubility or stability in a stable carrier particle. In addition, targeting nanoparticles to specific pathological sites may allow an increased effective dose of drug at the needed site, while decreasing systemic drug exposure, and therefore side effects. However, to date, only 2 nanoformulations for cancer treatment have been approved for clinical use (liposomal doxorubicin [Doxil] and protein-bound paclitaxel [Abraxane]) (1-3). One major obstacle for the use of nanoparticles in vivo is rapid clearance by the cells of the reticuloendothelial system (RES)/mononuclear phagocyte system (MPS) (4-7). In addition to rapid clearance, variable activity of the MPS among patients leads to widely variable pharmacokinetics of nanoformulations in the clinic, reducing the efficacy of both approved and future experimental nanoformulations (8).

show abstract

Section: Discussionmentioning

confidence: 99%

Nanoparticle clearance is governed by Th1/Th2 immunity and strain background

Jones¹,

Roberts²,

Robbins³

et al. 2013

J. Clin. Invest.

177

164

View full text Add to dashboard Cite

show abstract

“…The successful biomedical application of a nanomaterial is a reflection of its adequate design. Several factors should be taken into account such as size [13][14][15], shape [16], surface charge [17] and surface modification [18], to list but a few. Regarding surface modification (e.g., coating [13]), coating the nanomaterial with a polymeric coating reduces protein adsorption to nanomaterial surface and subsequently can reduce the nanomaterial clearance from the circulation through opsonization process.…”

Section: Introductionmentioning

confidence: 99%

Polymer-Coated Superparamagnetic Iron Oxide Nanoparticles as T ₂ Contrast Agent for MRI and their Uptake in Liver

et al. 2017

View full text Add to dashboard Cite

Aim:To study the efficiency of multifunctional polymer-based superparamagnetic iron oxide nanoparticles (bioferrofluids) as a T 2 magnetic resonance contrast agent and their uptake and toxicity in liver. Materials & methods: Mice were intravenously injected with bioferrofluids and Endorem R . The magnetic resonance efficiency, uptake and in vivo toxicity were investigated by means of magnetic resonance imaging (MRI) and histological techniques. Results: Bioferrofluids are a good T 2 contrast agent with a higher r 2 /r 1 ratio than Endorem. Bioferrofluids have a shorter blood circulation time and persist in liver for longer time period compared with Endorem. Both bioferrofluids and Endorem do not generate any noticeable histological lesions in liver over a period of 60 days post-injection. Conclusion: Our bioferrofluids are powerful diagnostic tool without any observed toxicity over a period of 60 days post-injection.Lay abstract: Several superparamagnetic iron oxide nanoparticles (SPIONs) preparations have been approved by US FDA for clinical use as MRI contrast agents. In recent years, we have been developing a synthetic multifunctional platform for SPIONs based on the use of polymers. In this report, we explored the diagnostic potential of these nanoparticles (herein called bioferrofluids) as an MRI contrast agent and their uptake in liver, without neglecting their toxicological effects. Results show that our bioferrofluids are a good T 2 contrast agent without any observed toxicity in liver.

show abstract

“…Thus size-dependent uptake of various NPs has been intensively investigated and widely reported. For example, for organic NPs, some researchers claimed smaller NPs resulted in higher cellular uptake [22,33], while others reported an optimal size range for highest uptake [34][35][36][37]. Ross and Hui [38] even found linearly increasing cellular uptake of lipoplex in the size range of 35-2200 nm.…”

Section: Introductionmentioning

confidence: 99%

Particle size- and number-dependent delivery to cells by layered double hydroxide nanoparticles

Dong

Parekh

2015

Journal of Colloid and Interface Science

View full text Add to dashboard Cite

a b s t r a c tIt is well known that delivery efficiency to cells is highly dependent on particle size and the administered dose. However, there is a marked discrepancy in many reports, mainly due to the inconsistency in assessment of various parameters. In this particular research, we designed experiments using layered double hydroxide nanoparticles (LDH NPs) to specifically elucidate the effect of particle size, dose and dye loading manner on cellular uptake. Using the number of LDH NPs taken up by HCT-116 cells as the indicator of delivery efficiency, we found that (1) the size of sheet-like LDH in the range of 40-100 nm did not significantly affect their cellular uptake; (2) cellular uptake of 40 and 100 nm LDH NPs was increased proportionally to the number concentration below a critical value, but remained relatively constant beyond the critical value; and (3) the effect of the dye loading manner is mainly dependent on the loading capacity or yield. In particular, the loading capacity is determined by the NP specific surface area. This research may be extended to a larger size range to examine the size effect, but suggests that it is necessary to set up a protocol to evaluate the effects of NP's physicochemical properties on the cellular delivery efficiency.

show abstract

Effects of Particle Size and Surface Modification on Cellular Uptake and Biodistribution of Polymeric Nanoparticles for Drug Delivery

Abstract: TPGS-coated PS NPs of 100 and 200 nm sizes have potential to deliver the drug across the GI barrier and the BBB.

Cited by 632 publications

References 42 publications

Nanoparticle clearance is governed by Th1/Th2 immunity and strain background

Nanoparticle clearance is governed by Th1/Th2 immunity and strain background

Polymer-Coated Superparamagnetic Iron Oxide Nanoparticles as T ₂ Contrast Agent for MRI and their Uptake in Liver

Particle size- and number-dependent delivery to cells by layered double hydroxide nanoparticles

Contact Info

Product

Resources

About

Effects of Particle Size and Surface Modification on Cellular Uptake and Biodistribution of Polymeric Nanoparticles for Drug Delivery

Abstract: TPGS-coated PS NPs of 100 and 200 nm sizes have potential to deliver the drug across the GI barrier and the BBB.

Cited by 632 publications

References 42 publications

Nanoparticle clearance is governed by Th1/Th2 immunity and strain background

Nanoparticle clearance is governed by Th1/Th2 immunity and strain background

Polymer-Coated Superparamagnetic Iron Oxide Nanoparticles as T 2 Contrast Agent for MRI and their Uptake in Liver

Particle size- and number-dependent delivery to cells by layered double hydroxide nanoparticles

Contact Info

Product

Resources

About

Polymer-Coated Superparamagnetic Iron Oxide Nanoparticles as T ₂ Contrast Agent for MRI and their Uptake in Liver