Akina’s first polymer educational video is live. Polymers 101: What is a Polymer?
Akina’s first polymer educational video is live. Polymers 101: What is a Polymer?
Akina’s first polymer educational video is live. Polymers 101: What is a Polymer?
One promising area of research in cancer therapy is the development of theranostics. This area of research focuses on simultaneous application of both a therapeutic agent (typically a chemotherapeutic agent such as paclitaxel) and a diagnostic agent (typically a contrast agent or fluorescent dye which renders the tumor ‘visible’). This research requires highly advanced delivery systems which can ensure that the tumor receives a suitable quantity of both agents such that it becomes visible to a surgeon as well as receives an effective dose of the therapeutic agent. In a fundamental sense, this requires well-designed nanocarriers with high loading efficiency (large doses of each agent) and which are highly stable in the bloodstream. Recently, researchers at Wroclaw University (Poland) utilized a series of PolySciTech (www.polyscitech.com) polymers including mPEG-PCL (PolyVivo Cat# AK128), mPEG-PLA (PolyVivo Cat# AK056), and mPEG-PLGA (PolyVivo Cat# AK037) to systematically generate a series of test-loaded nanoparticles containing model DNA and fluorescent dye Thiazole Orange. The researchers systematically investigated all steps involved in nanoparticle formation and tested the particles for their stability, loading capacity, and other parameters relevant to their clinical usage. This research holds promise for the development of highly advanced nanocarriers to assist in theranostic treatments of a wide variety of cancers. Read more: Bazylińska, Urszula. “Rationally designed double emulsion process for co-encapsulation of hybrid cargo in stealth nanocarriers.” Colloids and Surfaces A: Physicochemical and Engineering Aspects (2017). http://www.sciencedirect.com/science/article/pii/S092777571730359X
“Abstract: Double emulsion process has become highly promising for development of PEG-ylated nanocarriers (NCs) with co-encapsulated hybrid model agents, i.e, hydrophilic deoxyribonucleic acid (DNA) and hydrophobic Thiazole Orange (TO) dye, in the double compartment structure to protect them from the environmental conditions and to investigate different parameters affecting the size, charge and morphology as well as colloidal and biological stability of the final theranostic nanosystems. Different stabilizing agents including surfactants: Cremophor A25, Cremophor RH 40, Poloxamer 407, di-C12DMAB as well as polymers: PEG-PDLLA, PEG-PLGA, PEG-PCL, were screened to choose suitable ones for this approach. The average size of the synthesized NCs measured by dynamic light scattering (DLS) remained < 200 nm. The encapsulation efficiency of the hybrid cargo was confirmed by UV-Vis spectroscopy. Morphology and shape of the loaded nanocontainers were investigated by transmission electron microscopy (TEM) and atomic force microscopy (AFM). Time-depended colloidal stability studies with DLS and ζ-potential followed by turbidimetric technique allow to select only the long-term nanosystems to final investigation the “stealth” properties of the fabricated PEGylated NCs. Highlights: Double emulsion process has become easy-scalable synthetic approach to develop “stealth” nanocarriers (NCs) successful in DNA and TO co-encapsulation. PEG-PDLLA, PEG-PLGA, PEG-PCL acted as pre-approved biocompatible components of the NCs polymer shell.The optimized encapsulation process resulted in NCs with diameter < 200 nm, narrow size distribution and nearly neutral surface. DLS, ζ-potential and backscattering studies confirmed a long-term NCs stability, indicating their potential as theranostic biocompatible agents. The biological stability exposed the PEG-ylated NCs ability to overcome various specific barriers to efficient drug and gene delivery. Keywords: w/o/w emulsions; PEG-ylated polyesters; DNA; Thiazole Orange; colloidal stability. Fabrication method: Polymeric nanocarriers stabilized by PEG-PLGA, PEG-PCL, PEG-PDLLA and non-ionic or cationic surfactants for co-encapsulation of therapeutic (model DNA in the initial concentration of 0.1 mg/ml) and diagnostic agent (TO in the initial concentration of 0.2 mg/ml) were prepared by modified double emulsion (w/o/w) evaporation process without any pH adjustment . Generally, aqueous internal phase (with DNA) was emulsified for 5 min in dichloromethane (containing TO, PEG-ylated polymer in concentration of 5 mg/ml and di-C12DMAB) in the ratio 1:4 using a homogenizer with 25,000 rpm. This primary nanoemulsion was poured into 1% hydrophilic surfactant solution (Cremophor A25, Cremophor RH 40 or Poloxamer 407) aqueous solution stirring in a homogenizer for 10 min (25,000 rpm) and immersed in an ice water bath to create the water-in-oil-in-water (w/o/w) emulsion. The organic solvent was then evaporated under reduced pressure in a rotary evaporator (Ika RV 10 digital) and polymeric nanocarriers loaded by the hybrid cargo were collected overnight.”
A fundamental difficulty with medicinal applications to humans is that the circulatory systems of most living organisms are designed specifically to screen out any perceived toxins or ‘non-self’ components. Typically, the kidneys and the liver work together along with macrophages (white blood cells) to remove any chemicals or particulates from the bloodstream. Although this system provides protection to the human body from toxic ingestion, it creates great difficulty for applying medicines as it greatly reduces the blood circulation time of medicinal molecules. For general medicinal applications, the loss of drug from the bloodstream is calculated as the circulation half-life and dosing schedules are calculated to match. One method to improve blood-circulation is to encapsulate the drug molecule inside of PEG-PLA so-called ‘stealth’ nanoparticles. For these particles, the PEG external coating prevents attacks by macrophages while the size alone reduces uptake and clearance by kidneys or liver. These particles enhance the blood circulation time of medicines, but a key question is by exactly how much is the blood circulation time enhanced and what is the new circulation half-life. This question critical for practical applications as it would define the dosing schedule of the encapsulated drug as it must be dosed often enough to maintain effect but not too often so as to potentially have toxic side-effects. Recently, researchers at Yale University utilized mPEG-PLA from PolySciTech (www.polyscitech.com) (PolyVivo Cat# AK054) to generate stealth-nanoparticles as test substrates for their novel fluorescence microscopy-based technique for determining half-life of particles using as little as 2 uL of blood. This research holds promise for rapid and routine determination of half-life using very small samples of blood. Read more: Tietjen, Gregory T., Jenna DiRito, Jordan S. Pober, and W. Mark Saltzman. “Quantitative microscopy-based measurements of circulating nanoparticle concentration using microliter blood volumes.” Nanomedicine: Nanotechnology, Biology and Medicine (2017). http://www.sciencedirect.com/science/article/pii/S1549963417300643
“Abstract: Nanoparticles (NPs) are potential drug delivery vehicles for treatment of a broad range of diseases. Intravenous (IV) administration, the most common form of delivery, is relatively non-invasive and provides (in theory) access throughout the circulatory system. However, in practice, many IV injected NPs are quickly eliminated by specialized phagocytes in the liver and spleen. Consequently, new materials have been developed with the capacity to significantly extend the circulating half-life of IV administered NPs. Unfortunately, current procedures for measuring circulation half-lives are often expensive, time consuming, and can require large blood volumes that are not compatible with mouse models of disease. Here we describe a simple and reliable procedure for measuring circulation half-life utilizing quantitative microscopy. This method requires only 2 μL of blood and minimal sample preparation, yet provides robust quantitative results. Graphical Abstract: Quantitative microscopy can be used to measure circulating concentrations of nanoparticles with as little as 2 μL of blood. However, when using such small volumes, the path length within and between samples can vary significantly as the high viscosity of blood can yield differences in think layer thickness as the blood spreads following application of a coverslip. This yields variability in the measured mean fluorescence intensity. Addition of a reference nanoparticle of a different color can correct the mean fluorescence intensity variance. Thus, quantitative microscopy can serve as a robust method for measuring nanoparticle half-life using μL volumes of blood. NP formulation: NP were prepared by a standard nanoprecipitation procedure. PLA–PEG (PolyVivo AK054) was dissolved at an initial concentration of 100 mg/mL in DMSO and then diluted to the desired concentration for NP formulation (typically ~55 mg/mL for the ~165 nm NPs used in this study) along with addition of either DiI or DiO dye also dissolved in DMSO. NPs were loaded with DiI or DiO dye at a final wt dye/wt polymer ratio of 0.5%. The dye/polymer solution in DMSO was added drop wise to vigorously stirring sterile diH2O in batches of 200 μL polymer/dye solution added to 1.3 mL of diH2O with identical repetitions performed to generate a full NP batch. NP were subsequently filtered through a 1.2 μm cellulose acetate membrane (GE Healthcare Life Sciences – Whatman) filter to remove any free dye or polymer aggregates and then pooled. Typically, 8 small batches of ~11 mg polymer each were combined for a total pooled batch size of ~88 mg initial polymer weight. The pooled NP solutions were then transferred to a 12 mL volume 10,000 MWCO dialysis cassettes (Thermo Scientific – Slide-A-Lyzer) and dialyzed against 2× exchanges of ~2.2 L of diH2O at room temperature to remove excess DMSO. Following dialysis NPs were aliquoted and snap frozen in liquid N2. One aliquot from each NP batch was lyophilized in a pre-weighed tube in order to determine the NP concentration. Standard NP concentration was typically ~5 mg/mL. NP batches were diluted to ~0.1 mg/mL and analyzed via dynamic light scattering (DLS) to confirm NP size and homogeneity.”
Sometimes research holds surprising results. Radical chain transfer is a process which allows for controlling the molecular weight and end-cap properties of poly(vinyl) type polymers. Conventionally, radical chain transfer agents comprise of molecules custom designed for that exact purpose, such as thiol compounds in which the sulfur atom actively participates in the free radical interaction. Conventionally, PLGA is not typically applied to free radical chain transfer however researchers at The University of Milan were able to use PLGA from PolySciTech (www.polyscitech.com) (PolyVivo cat# AP059) in this fashion to create PLGA-g-PVP. This research holds promise for the development of novel polymer compounds for a wide array of applications. Read more: Capuano, G. “Amphiphilic, Biodegradable and Biocompatible Polymers for Industrial Applications.” (2017). Universita Degli Studi Di Milano Facolta Di Scienze E Tecnologie PhD School in Industrial Chemistry XXIX Cycle PhD Student Capuano Giovanna Thesis. https://air.unimi.it/bitstream/2434/477898/2/phd_unimi_R10587.pdf
“The aim of this PhD work was to establish the synthetic procedures for new families of biocompatible and biodegradable and/or bioeliminable biomaterials that can be differently processed to obtain nanoparticles, core-shell nanof ibres and hydrogel slabs or conduits, respectively. Depending on composition, size and morphology, these biomaterials may be intended for applications as drug delivery systems and/or tissue regeneration. Specifically, the research project has been developed along two main lines: Synthesis of poly(lactic-glycolic acid)-g-poly(1-vinylpyrrolidin-2-one) (PLGA-g-PVP) copolymers whose architecture consisted of a long PLGA backbone with oligomeric PVP pendants. These were obtained by the radical polymerisation of 1-vinylpyrrolidin-2-one in molten PLGA 50:50, acting as chain transfer agent. Synthesis of a new classes of poly(saccharide)-poly(aminoamine)s 3D-network intended as scaffolds for the regeneration of liver. (Synthesis of PLGA-g-PVP): PLGA (2.012 g, PolyVivo AP059) and VP (0.203 g, 1.83 mol) were added to dichloromethane (30 mL) in a two-necked 100 mL flask equipped with a stir bar. The resultant solution was purged 5 min with nitrogen and AIBN (2.1 mg, 0.013 mmol) was added. Dichloromethane was then eliminated at room temperature and 0.2 tor. After three nitrogen-vacuum cycles, the reaction mixture was heated to 100 °C, maintained at this temperature under nitrogen for 2.5 h, cooled to room temperature and dissolved in dichloromethane (100 mL). The solution was poured drop-wise in diethyl ether (1 L) under vigorous stirring and the resultant slurry stirred for further 2 h. The precipitated product was finally retrieved by filtration, washed with fresh ether (200 mL) and dried under vacuum.”
Tissue engineering is an exciting field of research in which a cell scaffold is implanted to heal missing tissue. Normal human cells require a surface to adhere too and grow along. In the human body, this ‘surface’ is a group of cellular excretions, which give biochemical and mechanical (structural) support for the cells, referred to as the ‘extra cellular matrix’ (ECM). Without the ECM, cells cannot grow into the tissue. For this, and other reasons, damaged tissues will sometimes never regrow fully (e.g. amputations, defects, voids, etc.) The goal of tissue engineering is to find a way to replace the extra cellular matrix with a synthetic structure so that the surrounding cells can grow into the void area and replace it with new tissue. Recently, researchers at Pennsylvania State University published a patent in which PLLA from PolySciTech (www.polyscitech.com) (PolyVivo cat# AP047) was used as a control for bone-tissue replacement. This material, along with the experimental polymer, was processed into a porous structure by a method known as salt-leaching (see picture, Fig. 4B, for example). The examples of this patent provide excellent data regarding methodologies and use of this polymer in this application. Read more: Yang, Jian. “Methods of Promoting Bone Growth and Healing.” U.S. Patent 20170080125, issued March 23, 2017. http://www.freepatentsonline.com/y2017/0080125.html
“Abstract: In one aspect, methods of promoting bone growth are described herein. In some embodiments, a method described herein comprises disposing a graft or scaffold in a bone growth site. The graft or scaffold comprises (a) a polymer network formed from the reaction product of (i) citric acid, a citrate or an ester of citric acid with (ii) a polyol. The graft or scaffold further comprises (b) a particulate inorganic material dispersed in the polymer network.”
Near-infrared (NIR) is a frequency of light just outside of the range of human vision which can be seen through human flesh. The delivery of NIR fluorophores to cancer cells and other diseased tissues can provide for the opportunity to render cancer detectable through the skin by NIR fluorescent techniques. Recently, researchers at Wroclaw University (Poland) used PLGA from PolySciTech (PolyVivo AP062) to stabilize NIR active NaYF4:Er3+,Yb3 nanoparticles in a double emulsion along with nonionic surfactants. This research holds promise for allowing for improved cancer diagnostics by making tumors visible through the skin. Read more: Bazylińska, Urszula, and Dominika Wawrzyńczyk. “Encapsulation of TOPO stabilized NaYF 4: Er 3+, Yb 3+ nanoparticles in biocompatible nanocarriers: synthesis, optical properties and colloidal stability.” Colloids and Surfaces A: Physicochemical and Engineering Aspects (2017). http://www.sciencedirect.com/science/article/pii/S092777571730300X
“Abstract: The emulsification process leading to up-converting NaYF4:Er3+,Yb3+ NPs encapsulation, was performed using a modified water/oil/water double emulsion evaporation method, where poly(lactic-co-glycolic acid) was used as biocompatible polymer. Span 80 and Cremophor A25 were applied as non-ionic surfactants and dichloromethane as oily phase. The use of trioctylphosphine oxide ligands for the synthesis of up-converting NaYF4:Er3+,Yb3+ NPs allowed to obtain spherical particles with sizes below 10 nm, what further facilitated the efficient encapsulation process. Those newly designed nanosystems were subjected to analysis of their morphology, colloidal stability and optical properties by: dynamic light scattering, ζ-potential, atomic force microscopy, transmission electron microscopy and measuring the up-conversion emission spectra of free and loaded NaYF4:Er3+,Yb3+ NPs. The encapsulated NaYF4:Er3+,Yb3+ NPs showed increased colloidal stability for a long period of 60 days of storage in different conditions. Simultaneously, the encapsulation process did not significantly influenced their optical properties and strong visible emission could be observed upon nearinfrared excitation. Highlights: NaYF4:Er,Yb NPs ∼5 nm in size were synthesized with TOPO used as a stabilizing ligands. The modified double emulsion evaporation method was successful in the up-converting NPs encapsulation. PLGA, Span 80 and Cremophor A25 act as the obtained nanosystems stabilizers. The encapsulation process retain the optical properties of NaYF4:Er3+,Yb3+ NPs. The obtained nanocarriers have potential applications as theranostic agents.”
Lung cancer is among the leading causes of cancer-related death worldwide. Chrysin, a natural active flavone, acts to enhance the chemotherapeutic effectiveness of other chemoagents (cisplatin, docetaxel, etc.) against lung cancer. Chrysin’s usability, however, is limited by its very poor water solubility and low bioavailability. Recently, researchers at Duksung Women’s University (Korea) utilized mPEG-PCL from PolySciTech (www.polyscitech.com) (PolyVivo #: AK001) to formulate chrysin-loaded nanoparticles which were found to delay tumor progression in a mouse model. This research holds promised for improved lung-cancer therapy. Read more: Kim, Kyoung Mee, Hyun Kyung Lim, Sang Hee Shim, and Joohee Jung. “Improved chemotherapeutic efficacy of injectable chrysin encapsulated by copolymer nanoparticles.” International Journal of Nanomedicine 12 (2017): 1917. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352247/
“Abstract: Chrysin is a flavone that is found in several plants and in honeycomb and possesses various biological activities. However, its low solubility means it has poor bioavailability, which must be resolved to enable its pharmaceutical applications. In the present study, chrysin was incorporated into methoxy poly(ethylene glycol)-β-polycaprolactone nanoparticles (chrysin-NPs) using the oil-in-water technique in order to overcome problems associated with chrysin. The properties of chrysin-NPs were analyzed, and their anticancer effects were investigated in vitro and in vivo. Chrysin-NPs were 77 nm sized (as determined by dynamic laser light scattering) and showed a monodisperse distribution. The zeta potential of chrysin-NPs was −2.22 mV, and they were spherically shaped by cryo-transmission electron microscopy (cryo-TEM). The loading efficiency of chrysin-NPs was 46.96%. Chrysin-NPs retained the cytotoxicity of chrysin in A549 cells. The therapeutic efficacies of chrysin-NPs were compared with those of chrysin in an A549-derived xenograft mouse model. Chrysin-NPs were intravenously injected at a 10 times lower dosage than chrysin 3 times per week (q2d×3/week). However, free chrysin was orally administrated 5 times per week (q1d×5/week). Chrysin-NP-treated group showed significant tumor growth delay, which was similar to that of chrysin-treated group, despite the considerably lower total dosage. These results suggest that the injectable chrysin-NPs enhance therapeutic efficacy in vivo and offer a beneficial formulation for chemotherapy. Keywords: chrysin, nanoparticle, chemotherapeutic efficacy, non-small-cell lung cancer, in vivo model. Nanoparticle preparation method: Chrysin (Sigma-Aldrich, St Louis, MO, USA) was incorporated into copolymer NPs using an oil-in-water technique (Figure 1). mPEG–β-polycaprolactone copolymer (mPEG-PCL, 50 mg; 2,000:5,200 Da; PolySciTech, West Lafayette, IN, USA) and 5 mg of chrysin were dissolved in a dichloromethane (Duksan reagent, Gyeonggi-do, Korea) and methanol mixture (Duksan reagent; v/v, 1.5:1). This solution (2.5 mL) was added to a 1% aqueous polyvinyl alcohol solution (6 mL) and was emulsified by sonification for 1 min. The solvent was removed by evaporation under stirring to produce NPs. To remove polyvinyl alcohol and surplus free chrysin, the supernatant was collected after centrifugation (14,000 rpm) twice at room temperature for 1 h.”
A relatively recent and powerful tool for both manufacturing and research has been developed in 3D printing. Despite it’s advantages, 3D printing is restricted based on the polymeric material’s melt and processing properties. Recently, researchers working jointly at University of Maryland, Cornell University, and Rice University screened through a series of PLGA materials in order to define the optimal printing procedures for each. The utilized a series of PLGA’s from PolySciTech (www.polyscitech.com) (PolyVivo AP039, AP137, AP076, and AP024) and optimized their printing configurations for bone-tissue engineering. This research holds promise for the capability to print biocompatible, biodegradable parts for tissue engineering and other applications. Read more at: Guo, Ting, Timothy Holzberg, Casey Lim, Feng Gao, Ankit Gargava, Jordan Trachtenberg, Antonios Mikos, and John Fisher. “3D printing PLGA: a quantitative examination of the effects of polymer composition and printing parameters on print resolution.” Biofabrication (2017). http://iopscience.iop.org/article/10.1088/1758-5090/aa6370/meta
“Abstract: In the past few decades, 3D printing has played a significant role in fabricating scaffolds with consistent, complex structure that meets patient-specific needs in future clinical applications. Although many studies have contributed to this emerging field of additive manufacturing, which includes material development and computer-aided scaffold design, current quantitative analyses do not correlate material properties, printing parameters, and printing outcomes to a great extent. A model that correlates these properties has tremendous potential to standardize 3D printing for tissue engineering and biomaterial science. In this study, we printed poly(lactic-co-glycolic acid) (PLGA) utilizing a direct melt extrusion technique without additional ingredients. We investigated PLGA with various lactic acid:glycolic acid (LA:GA) molecular weight ratios and end caps to demonstrate the dependence of the extrusion process on the polymer composition. Micro-computed tomography (microCT) was then used to evaluate printed scaffolds containing different LA:GA ratios, composed of different fiber patterns, and processed under different printing conditions. We built a statistical model to reveal the correlation and predominant factors that determine printing precision. Our model showed a strong linear relationship between the actual and predicted precision under different combinations of printing conditions and material compositions. This quantitative examination establishes a significant foreground to 3D print biomaterials following a systematic fabrication procedure. Additionally, our proposed statistical models can be applied to couple specific biomaterials and 3D printing applications for patient implants with particular requirements.”
One of the goals within controlled delivery is to provide for targeted medicinal delivery in which the medicine is guided to the site that it is needed in by natural processes. More specifically, in cancer, there is a need to delivery nanoparticles to the tumor site for both therapy (medicinal delivery) as well as diagnosis (contrast agent delivery). Recently, researchers at Chongqing Medical University (China) used PolySciTech (www.polyscitech.com) product PLGA-PEG-COOH (PolyVivo AI056) and conjugated on Herceptin (antibody which conjugates to breast cancer tumors) to target it towards breast cancer cells. They formulated these with both contrast agents and chemotherapeutic paclitaxel. This research holds promise for improved breast-cancer therapy. Read more: Song, Weixiang, Yindeng Luo, Yajing Zhao, Xinjie Liu, Jiannong Zhao, Jie Luo, Qunxia Zhang, Haitao Ran, Zhigang Wang, and Dajing Guo. “Magnetic nanobubbles with potential for targeted drug delivery and trimodal imaging in breast cancer: an in vitro study.” Nanomedicine 0 (2017). http://www.futuremedicine.com/doi/abs/10.2217/nnm-2017-0027
“Aim: The aim of this study was to improve tumor-targeted therapy for breast cancer by designing magnetic nanobubbles with the potential for targeted drug delivery and multimodal imaging. Materials & methods: Herceptin-decorated and ultrasmall superparamagnetic iron oxide (USPIO)/paclitaxel (PTX)-embedded nanobubbles (PTX-USPIO-HER-NBs) were manufactured by combining a modified double-emulsion evaporation process with carbodiimide technique. PTX-USPIO-HER-NBs were examined for characterization, specific cell-targeting ability and multimodal imaging. Results: PTX-USPIO-HER-NBs exhibited excellent entrapment efficiency of Herceptin/PTX/USPIO and showed greater cytotoxic effects than other delivery platforms. Low-frequency ultrasound triggered accelerated PTX release. Moreover, the magnetic nanobubbles were able to enhance ultrasound, magnetic resonance and photoacoustics trimodal imaging. Conclusion: These results suggest that PTX-USPIO-HER-NBs have potential as a multimodal contrast agent and as a system for ultrasound-triggered drug release in breast cancer.”
Chemoradiotherapy is a cancer therapy technique in which a sensitizer molecule is administered to a patient prior to administration of a dose of radiation. Typically, such a technique is made difficult as the sensitizer molecule can affect both tumor tissue and normal tissue, causing more damage from radiation. However, with the application of localized-delivery to the tumor, this technique holds great potential for cancer therapy by allowing specific and selective destruction of tumor tissue at a relatively lower dose of radiation. Recently, researchers at the University of North Carolina Chapel Hill utilized PolySciTech (www.polyscitech.com) mPEG-PLGA’s (PolyVivo AK010, AK023) and fluorescently-tagged polymer PLGA-rhodamine B (PolyVivo AV011) for development of an advanced nanoparticle delivery system for Wortmannin (DNA-PK inhibitor) or novel KU60019 (ATM inhibitor) molecules. Both of these molecules act to increase local radiation damage to tumors by preventing DNA repair. The researchers found that smaller particles were more effective at avoiding hepatic clearance but medium sized particles showed more efficacy for sensitization. This research holds promise for enhanced cancer treatment techniques. Read more: Caster, Joseph M., K. Yu Stephanie, Artish N. Patel, Nicole J. Newman, Zachary J. Lee, Samuel B. Warner, Kyle T. Wagner et al. “Effect of particle size on the biodistribution, toxicity, and efficacy of drug-loaded polymeric nanoparticles in chemoradiotherapy.” Nanomedicine: Nanotechnology, Biology and Medicine (2017). http://www.sciencedirect.com/science/article/pii/S1549963417300448
“Abstract: Nanoparticle (NP) therapeutics can improve the therapeutic index of chemoradiotherapy (CRT). However, the effect of NP physical properties, such particle size, on CRT is unknown. To address this, we examined the effects of NP size on biodistribution, efficacy and toxicity in CRT. PEG-PLGA NPs (50, 100, 150 nm mean diameters) encapsulating wotrmannin (wtmn) or KU50019 were formulated. These NP formulations were potent radiosensitizers in vitro in HT29, SW480, and lovo rectal cancer lines. In vivo, the smallest particles avoided hepatic and splenic accumulation while more homogeneously penetrating tumor xenografts than larger particles. However, smaller particles were no more effective in vivo. Instead, there was a trend towards enhanced efficacy with medium sized NPs. The smallest KU60019 particles caused more small bowel toxicity than larger particles. Our results showed that particle size significantly affects nanotherapeutics’ biodistrubtion and toxicity but does not support the conclusion that smaller particles are better for this clinical application. Graphical Abstract: Sub50 nm drug-loaded NPs avoid hepatic clearance and more homogeneously distribute within tumors. However, they are no more efficacious and are associated with more small bowel toxicity than larger particles. Keywords: Nanoparticle; Chemoradiotherapy; Nanoparticle radiosensitization; KU60019; Wortmannin”