Scalable Fabrication of Low Elastic Modulus Polymeric Nanocarriers With Controlled Shapes for Diagnostics and Drug Delivery

Singh, Vedant; Agarwal, Rachit; Marshall, K. Scott; Roy, Krishnendu; Shi, Li; Sreenivasan, Sameet

doi:10.1115/1.4028896

Cited by 5 publications

(7 citation statements)

References 42 publications

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“…Yellow (and their corresponding bars) represents our and commonly used stabilizers, while red (and their corresponding bars) is denoted as commonly reported materials in synthesizing biodegradable and/or nonspherical nanoparticles for drug delivery and targeting. Abbreviations and further details of referred material–nanoparticles: SDS (sodium dodecyl sulfate), (2) Docusate‐Na, (3) Triton X‐100, (4) Na‐Cholate & ‐Deoxycholate, (5) PVP (poly(vinylpyrrolidone)), (6) PEG (poly(ethylene glycol)) 6000, (7) Dextran, (8) Poloxamer 188, (9) HSA (human serum albumin), (10) Chitosan, (11) Cyanoacrylate, (12) PS‐COOH (carboxylated poly(styrene)), (13) PS (poly(styrene)), (14) PDMS (poy(dimethylsiloxane)), (15) PMMA (poly(methyl methacrylate)), (16) PHEA (poly(hydroxyethyl acrylate)), (17) PHEMA (poly(hydroxyethyl methacrylate)), (18) PEGDA (poly(ethylene glycol) diacrylate)‐PHEMA (poly(hydroxyethyl methacrylate)), (19) CEA (2‐carboxyethyl acrylate), (20) PBLG (poly(γ‐benzyl l ‐glutamate)), (21) Triglyceride (cocoa butter), (22) P4VP (poly(4‐vinyl pyridine)), (23) Au (gold), and (24) SWCNT (single‐walled carbon nanotubes) …”

Section: Resultsmentioning

confidence: 99%

“…We have tried to harvest both nonspherical cross‐linked hydrogel nanoparticles from PVA (Mowiol 40‐88) film using only HPW (pH 5.5–5.8) as well, however, the exaggerate swelling still occurred (similar appearances like in Figure b). The considerable swelling in the nonspherical cross‐linked hydrogel nanoparticles by the film‐stretching method may be explained by the facts that swelling is more pronounced in the cases of smaller submicron (i.e., size ≤ 200 nm), less cross‐linked (for O‐CMCHS), and heated particles . From these findings, it can also be inferred that swelling is actually displayed by hydrogel particles prepared by any materials (e.g., poly(hydroxyethyl acrylate) /PHEA, poly(ethylene glycol) diacrylate /PEGDA, derivatives of hydroxyl PEG acrylate groups, etc.)…”

Section: Discussionmentioning

confidence: 97%

“…From these findings, it can also be inferred that swelling is actually displayed by hydrogel particles prepared by any materials (e.g., poly(hydroxyethyl acrylate) /PHEA, poly(ethylene glycol) diacrylate /PEGDA, derivatives of hydroxyl PEG acrylate groups, etc.) and methods (i.e., imprint lithography, irrespective from its subtypes, particle replication in nonwetting templates [PRINT], etc. ), but they are in the much lesser degree.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the strong interaction between hydrophobic part of gelatin and PVA was utilized to develop gelatin nanoparticles without crosslink . The remarkable interaction may also occur between PVA and other hydrogel systems, such as lithography (e.g., S‐FIL, J‐FIL, and D‐FIL) or PRINT ® method.…”

Section: Discussionmentioning

confidence: 99%

“…Classically, particle shape has been disregarded as a feature, which may switch the biodistribution and circulation half‐life. Sundry manufacturing methods, such as mechanical stretching, lithography, nonwetting templates, and microfluidics, enable the preparation of nonspherical nanoparticles and entitle the further investigation of particle geometry's influence on biological half‐life and fate. It has been demonstrated that (prolate) ellipsoid particles display a lower internalization by macrophages .…”

Section: Introductionmentioning

confidence: 99%

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Nonspherical Nanoparticle Shape Stability Is Affected by Complex Manufacturing Aspects: Its Implications for Drug Delivery and Targeting

Haryadi

Hafner

Amin

et al. 2019

Adv Healthcare Materials

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The shape of nanoparticles is known recently as an important design parameter influencing considerably the fate of nanoparticles with and in biological systems. Several manufacturing techniques to generate nonspherical nanoparticles as well as studies on in vitro and in vivo effects thereof have been described. However, nonspherical nanoparticle shape stability in physiological‐related conditions and the impact of formulation parameters on nonspherical nanoparticle resistance still need to be investigated. To address these issues, different nanoparticle fabrication methods using biodegradable polymers are explored to produce nonspherical nanoparticles via the prevailing film‐stretching method. In addition, systematic comparisons to other nanoparticle systems prepared by different manufacturing techniques and less biodegradable materials (but still commonly utilized for drug delivery and targeting) are conducted. The study evinces that the strong interplay from multiple nanoparticle properties (i.e., internal structure, Young's modulus, surface roughness, liquefaction temperature [glass transition (Tg) or melting (Tm)], porosity, and surface hydrophobicity) is present. It is not possible to predict the nonsphericity longevity by merely one or two factor(s). The most influential features in preserving the nonsphericity of nanoparticles are existence of internal structure and low surface hydrophobicity (i.e., surface‐free energy (SFE) > ≈55 mN m−1, material–water interfacial tension <6 mN m−1), especially if the nanoparticles are soft (<1 GPa), rough (Rrms > 10 nm), porous (>1 m2 g−1), and in possession of low bulk liquefaction temperature (<100 °C). Interestingly, low surface hydrophobicity of nanoparticles can be obtained indirectly by the significant presence of residual stabilizers. Therefore, it is strongly suggested that nonsphericity of particle systems is highly dependent on surface chemistry but cannot be appraised separately from other factors. These results and reviews allot valuable guidelines for the design and manufacturing of nonspherical nanoparticles having adequate shape stability, thereby appropriate with their usage purposes. Furthermore, they can assist in understanding and explaining the possible mechanisms of nonspherical nanoparticles effectivity loss and distinctive material behavior at the nanoscale.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Nonspherical Nanoparticle Shape Stability Is Affected by Complex Manufacturing Aspects: Its Implications for Drug Delivery and Targeting

Haryadi

Hafner

Amin

et al. 2019

Adv Healthcare Materials

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Effect of Shape, Size, and Aspect Ratio on Nanoparticle Penetration and Distribution inside Solid Tissues Using 3D Spheroid Models

Agarwal

Jurney

Raythatha

et al. 2015

Adv Healthcare Materials

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124

102

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Efficient penetration and uniform distribution of nanoparticles (NPs) inside solid tissues and tumors is paramount to their therapeutic and diagnostic success. While many studies have reported the effect of NP size and charge on intratissue distribution, role of shape, and aspect ratio on NP transport inside solid tissues remain unclear. Here experimental and theoretical studies are reported on how nanoscale geometry of Jet and Flash Imprint Lithography-fabricated, polyethylene-glycol-based anionic nanohydrogels affect their penetration and distribution inside 3D spheroids, a model representing the intervascular region of solid, tumor-like tissues. Unexpectedly, low aspect ratio cylindrical NPs (H/D ≈0.3; disk-like particles, 100 nm height, and 325 nm diameter) show maximal intratissue delivery (>50% increase in total cargo delivered) and more uniform penetration compared to nanorods or smaller NPs of the same shape. This is in contrast to spherical NPs where smaller NP size resulted in deeper, more uniform penetration. Our results provide fundamental new knowledge on NP transport inside solid tissues and further establish shape and aspect ratio as important design parameters in developing more efficient, better penetrating, nanocarriers for drug, or contrast-agent delivery.

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Influence of discrete drop locations on film thickness uniformity in UV- nanoimprint lithography

Singhal

Sreenivasan

2016

Microelectronic Engineering

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Multi-nozzle inkjetting is the material deposition approach for a variant of UVnanoimprint lithography called Jet-and-Flash Imprint Lithography (J-FIL). J-FIL has several advantages with respect to addressing pattern density variations in the template as well as achieving low material waste when compared with spin-coating. In this work, the influence of discrete drop placement in J-FIL on residual layer thickness uniformity has been investigated with the help of a novel nonlinear lubrication theory model, which takes into account the compliant nature of the template in the presence of a moving contact line. This work is directed at thin residual layers (sub-20 nm), where a correlation exists between minimum drop resolution, inkjet nozzle pitch and residual layer thickness uniformity. Numerical simulations reveal that the non-uniformity resulting from discrete drop placement can exceed desired process tolerances when low film thicknesses are desired with relatively larger drop volumes. The results have been verified experimentally to reveal the same trend. This work can be useful in determining the correlation of inkjet drop resolution with inkjet nozzle pitch to meet process tolerances in the J-FIL process.

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Scalable Fabrication of Low Elastic Modulus Polymeric Nanocarriers With Controlled Shapes for Diagnostics and Drug Delivery

Cited by 5 publications

References 42 publications

Nonspherical Nanoparticle Shape Stability Is Affected by Complex Manufacturing Aspects: Its Implications for Drug Delivery and Targeting

Nonspherical Nanoparticle Shape Stability Is Affected by Complex Manufacturing Aspects: Its Implications for Drug Delivery and Targeting

Effect of Shape, Size, and Aspect Ratio on Nanoparticle Penetration and Distribution inside Solid Tissues Using 3D Spheroid Models

Influence of discrete drop locations on film thickness uniformity in UV- nanoimprint lithography

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