Shape control in engineering of polymeric nanoparticles for therapeutic delivery

Williford, John-Michael; Santos, José Lúıs; Shyam, Rishab; Mao, Hai‐Quan

doi:10.1039/c5bm00006h

Cited by 98 publications

(89 citation statements)

References 135 publications

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“…Furthermore, biologically relevant in vitro assays, standardized in vivo experiments, quantifiable biodistribution NP statistics, and assessment in larger animal models are needed to fully characterize NP size effect. This will in turn spawn discoveries of other NP parameters important for biological fate such as shape [116]. As NP-size related physiological effects are understood better, engineering more efficient drug/vaccine delivery systems and imaging modalities will be possible, therefore accelerating the translation from laboratories to the clinic in diagnosis and treatment of various diseases.…”

Section: Discussionmentioning

confidence: 99%

Control of polymeric nanoparticle size to improve therapeutic delivery

Hickey

Santos

Williford

et al. 2015

Journal of Controlled Release

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287

199

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As nanoparticle (NP)-mediated drug delivery research continues to expand, understanding parameters that govern NP interactions with the biological environment becomes paramount. The principles identified from the study of these parameters can be used to engineer new NPs, impart unique functionalities, identify novel utilities, and improve the clinical translation of NP formulations. One key design parameter is NP size. New methods have been developed to produce NPs with increased control of NP size between 10 to 200 nm, a size range most relevant to physical and biochemical targeting through both intravascular and site-specific deliveries. Three notable techniques best suited for generating polymeric NPs with narrow size distributions are highlighted in this review: self-assembly, microfluidics-based preparation, and flash nanoprecipitation. Furthermore, the effect of NP size on the biological fate and transport properties at the molecular scale (protein-NP interactions) and the tissue and systemic scale (convective and diffusive transport of NPs) are analyzed here. These analyses underscore the importance of NP size control in considering clinical translation and assessment of therapeutic outcomes of NP delivery vehicles.

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Section: Discussionmentioning

confidence: 99%

Control of polymeric nanoparticle size to improve therapeutic delivery

Hickey

Santos

Williford

et al. 2015

Journal of Controlled Release

Self Cite

287

199

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show abstract

“…Several methodologies have been proposed to produce particles with complex shapes. [89][90][91][92][93] One versatile technique proposed by Mitragotri's group permitted to obtain a wide range of particles shapes comprising sizes between 60 nm and 30 µm, based on the stretching of spherical particles. [ 91 ] Polyvinyl alcohol fi lms prepared from a suspension containing spherical polymeric particles were stretched enabling the production of particles with different shapes.…”

Section: Reviewmentioning

confidence: 99%

Design Advances in Particulate Systems for Biomedical Applications

Lima

Álvarez-Lorenzo

Mano

2016

Adv Healthcare Materials

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Particulate systems have been widely used as containers of drugs or cells with the purpose of releasing them in a particularThe search for more effi cient therapeutic strategies and diagnosis tools is a continuous challenge. Advances in understanding the biological mechanisms behind diseases and tissues regeneration have widened the fi eld of applications of particulate systems. Particles are no more just protective systems for the encapsulated drugs, but they play an active role in the success of the therapy. Moreover, particles have been explored for innovative purposes as templates for cells growth and as diagnostic tools. Until few years ago the most relevant parameters in particles formulation were the chemistry and the size. Currently, it is known that other physical characteristics can remarkably affect the performance of particulate systems. Particles with non-conventional shapes exhibit advantages due to the increasing circulation time in blood stream, less clearance by the immune system and more effi cient cell internalization and traffi cking. Creation of compartments has been found useful to control drug release, to tune the transport of substances across biological barriers, to supply the target with more than one bioactive agent or even to act as theranostic systems. It is expected that such complex shaped and compartmentalized systems improve the therapeutic outcomes and also the patient's compliance, acting as advanced devices that serve for simultaneous diagnosis and treatment of the disease, combining agents of very different features, at the same time. In this review, we overview and analyse the most recent advances in particle shape and compartmentalization and applications of newly designed particulate systems in the biomedical fi eld.

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“…In addition, previous results suggest that with sufficient PEG grafting degree, shorter PEG chains may still be used to control the shape of polymer/DNA nanoparticles, 37 a potential important parameter for in vivo application given the demonstrated importance of nanoparticle shape on cellular uptake, tissue diffusion, and transport properties in several recent studies. 41−44 …”

Section: Introductionmentioning

confidence: 99%

Critical Length of PEG Grafts on lPEI/DNA Nanoparticles for Efficient in Vivo Delivery

Williford

Archang²,

Minn

et al. 2016

ACS Biomater. Sci. Eng.

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Nanoparticle-mediated gene delivery is a promising alternative to viral methods; however, its use in vivo, particularly following systemic injection, has suffered from poor delivery efficiency. Although PEGylation of nanoparticles has been successfully demonstrated as a strategy to enhance colloidal stability, its success in improving delivery efficiency has been limited, largely due to reduced cell binding and uptake, leading to poor transfection efficiency. Here we identified an optimized PEGylation scheme for DNA micellar nanoparticles that delivers balanced colloidal stability and transfection activity. Using linear polyethylenimine (lPEI)-g-PEG as a carrier, we characterized the effect of graft length and density of polyethylene glycol (PEG) on nanoparticle assembly, micelle stability, and gene delivery efficiency. Through variation of PEG grafting degree, lPEI with short PEG grafts (molecular weight, MW 500–700 Da) generated micellar nanoparticles with various shapes including spherical, rodlike, and wormlike nanoparticles. DNA micellar nanoparticles prepared with short PEG grafts showed comparable colloidal stability in salt and serum-containing media to those prepared with longer PEG grafts (MW 2 kDa). Corresponding to this trend, nanoparticles prepared with short PEG grafts displayed significantly higher in vitro transfection efficiency compared to those with longer PEG grafts. More importantly, short PEG grafts permitted marked increase in transfection efficiency following ligand conjugation to the PEG terminal in metastatic prostate cancer-bearing mice. This study identifies that lPEI-g-PEG with short PEG grafts (MW 500–700 Da) is the most effective to ensure shape control and deliver high colloidal stability, transfection activity, and ligand effect for DNA nanoparticles in vitro and in vivo following intravenous administration.

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Shape control in engineering of polymeric nanoparticles for therapeutic delivery

Cited by 98 publications

References 135 publications

Control of polymeric nanoparticle size to improve therapeutic delivery

Control of polymeric nanoparticle size to improve therapeutic delivery

Design Advances in Particulate Systems for Biomedical Applications

Critical Length of PEG Grafts on lPEI/DNA Nanoparticles for Efficient in Vivo Delivery

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